Pavlos Katonis

Estimation of Patient Dose and Associated Radiogenic Risks From Fluoroscopically Guided Pedicle Screw Insertion

Study Design. An experimental model for the assessment of patient dose and associated radiogenic risks associated with pedicle screw internal fixation surgical procedures. Objectives. To provide data for the accurate determination of patient effective dose, gonadal dose, and entrance skin dose from fluoroscopically assisted pedicle screw insertion procedures and to investigate the potential of both stochastic and deterministic radiogenic effects to occur following such procedures. Summary of Background Data. There is increased concern on radiation exposure of patients undergoing fluoroscopically guided interventional procedures. Methods. The cumulative screening time and dose area product, for each fluoroscopic projection used, were monitored in 20 patients undergoing pedicle screw internal fixation. The dose absorbed by each radiosensitive organ/tissue was determined from direct measurements obtained using an anthropomorphic phantom appropriately loaded with thermoluminescence dosimeters. Results. An average pedicle screw insertion procedure requires 1.2 minutes and 2.1 minutes of fluoroscopic exposure along anteroposterior and lateral projections, respectively, resulting in a dose area product of 232 cGy cm2 and 568 cGy cm2, correspondingly. Gender-specific normalized data for the determination of effective, gonadal, and entrance skin dose to patients undergoing fluoroscopically guided pedicle screw internal fixation procedures were derived. The effective dose from an average procedure was 1.52 and 1.40 mSv and the gonadal dose 0.67 and 0.12 mGy for female and male patients, respectively. The average radiogenic risks for fatal cancer and genetic defects were 115 and 4 per million of patients treated, respectively. Induction of skin injuries might be induced when fluoroscopy along the lateral projection is highly extended and the source to skin distance is kept low. Conclusions. Patient dose and radiogenic risks associated with an average pedicle screw internal fixation procedure are tolerable. However, for young patients with complex spinal disorders requiring extended fluoroscopy, radiogenic risks may be considerable. Present data may beused for estimation of effective dose, gonadal dose, and entrance skin exposure and associated radiogenic risks to patients undergoing fluoroscopically guided pedicle screw insertion in any institution.

The innervation of the human meniscus.

Fourteen menisci from seven anatomic specimens were examined to identify their innervation. After staining by a modified gold chloride method, the menisci were sectioned on a sliding microtome and were studied under a light microscope. Free nerve endings in the peripheral and the medial thirds of the meniscal body were identified, and three types of encapsulated mechanoreceptors were found in the anterior and posterior horns. Based on these findings and a review of the relevant literature, it is considered that menisci both receive and transmit proprioceptive information. Therefore, they not only are stabilizers of this joint, but also contribute to the function of deep sensitivity.

Treatment of unstable thoracolumbar and lumbar spine injuries using Cotrel-Dubousset instrumentation.

STUDY DESIGN In this prospective study, the results of treating unstable thoracolumbar and lumbar injuries with Cotrel-Dubousset instrumentation were investigated. OBJECTIVE To determine the pain and work status of the patients, to evaluate neurologic status, and to assess the efficacy of instrumentation in the short term. SUMMARY OF BACKGROUND DATA Short-segment pedicle screw construct is the method of choice for reduction and stabilization of unstable thoracolumbar spinal injuries. Many investigators have recently reported a high rate of instrument failure. In this study, the use of segmental transpedicular fixation two levels above the kyphosis decreased instrument failure and sagittal collapse. METHODS Thirty patients, who had unstable thoracolumbar and lumbar spinal injuries, underwent application from a posterior approach of Cotrel-Dubousset instrumentation two levels above and one below at the thoracolumbar junction and short segment fixation in the lumbar area. Radiologic parameters were evaluated before and after surgery. RESULTS The mean follow up was 31 months (range, 25-49) months. There were statistically significant differences between the pre- and postoperative values in all radiologic parameters. Neurologic status improved in 70% of the patients, with a mean Frankel grade of 1.3 grades. CONCLUSIONS Cotrel-Dubousset instrumentation provided spinal stability in unstable injuries, forming a rigid construct and restoring physiologic thoracolumbar and lumbar postural contours because of its highly corrective effect in the sagittal profile with no loss of correction.

Minimally invasive surgery for ablation of osteoid osteoma of the spine.

Study Design. Compare the effectiveness of two different techniques for the management of osteoid osteoma of the spine. Objective. To describe the technique, feasibility, and indications of two different minimally invasive surgical methods for the treatment of osteoid osteoma of the spine. Summary of the Background Data. Current treatment of osteoid osteoma of the spine is usually conventional surgical excision. The successful treatment of osteoid osteoma of the appendicular skeleton by percutaneous radiofrequency probe ablation is known; however, there have been only a few cases reported utilizing this method to treat osteoid osteoma of the spine. The high success rate of percutaneous transpedicle vertebral biopsy and diskectomy led us to believe this technique can also be applicable for the treatment of osteoid osteoma of the spine. Methods. Two patients with symptomatic osteoid osteoma of the spine underwent two different surgical managements with local anesthesia. In one patient, the osteoid osteoma was localized in the apex of the right L4 superior articular process joint. Under computed tomography guidance he underwent radiofrequency coagulation with the use of a radiofrequency generator at 90° for 240 seconds. The lesion in the second patient was located in the right pedicle of the T9 vertebra close to the exiting nerve root and was cored out by means of a special percutaneous instrument designed for percutaneous biopsy under fluoroscopic guidance. Results. Both patients experienced immediate relief of pain, resumed their regular activities, and also remained free of symptoms after the 2.5- and 3-year follow-up. Conclusion. Minimally invasive surgery can successfully be applied in the treatment of osteoid osteoma of the lumbar spine. When the nidus is not adjacent to the neural elements radiofrequency thermal ablation can be an effective and safe treatment of osteoid osteoma in the spine.

Role of Receptor for Hyaluronic Acid-mediated Motility (RHAMM) in Low Molecular Weight Hyaluronan (LMWHA)-mediated Fibrosarcoma Cell Adhesion

Background: Hyaluronan (HA) modulates key cancer cell functions through interaction with its CD44 and RHAMM receptors. Results: Low molecular weight HA (LMWHA) significantly increased (p ≤ 0.01) the adhesion capacity of HT1080 cells in a RHAMM-dependent manner. Conclusion: RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways. Significance: Identification of a novel HA-signaling pathway. Hyaluronan (HA) modulates key cancer cell functions through interaction with its CD44 and receptor for hyaluronic acid-mediated motility (RHAMM) receptors. HA was recently found to regulate the migration of fibrosarcoma cells in a manner specifically dependent on its size. Here, we investigated the effect of HA/RHAMM signaling on the ability of HT1080 fibrosarcoma cells to adhere onto fibronectin. Low molecular weight HA (LMWHA) significantly increased (p ≤ 0.01) the adhesion capacity of HT1080 cells, which high molecular weight HA inhibited. The ability of HT1080 RHAMM-deficient cells, but not of CD44-deficient ones, to adhere was significantly decreased (p ≤ 0.001) as compared with control cells. Importantly, the effect of LMWHA on HT1080 cell adhesion was completely attenuated in RHAMM-deficient cells. In contrast, adhesion of RHAMM-deficient cells was not sensitive to high molecular weight HA treatment, which identifies RHAMM as a specific conduit of the LMWHA effect. Western blot and real time-PCR analyses indicated that LMWHA significantly increased RHAMM transcript (p ≤ 0.05) and protein isoform levels (53%, 95 kDa; 37%, 73 kDa) in fibrosarcoma cells. Moreover, Western blot analyses showed that LMWHA in a RHAMM-dependent manner enhanced basal and adhesion-dependent ERK1/2 and focal adhesion kinase (FAK) phosphorylation in HT1080 cells. Utilization of a specific ERK1/2 inhibitor completely inhibited (p ≤ 0.001) LMWHA-dependent adhesion, suggesting that ERK1/2 is a downstream effector of LMWHA/RHAMM signaling. Likewise, the utilization of the specific ERK1 inhibitor resulted in a strong down-regulation of FAK activation in HT1080 cells, which identifies ERK1/2 as a FAK upstream activator. In conclusion, our results suggest that RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways.

Complications and problems related to pedicle screw fixation of the spine.

This retrospective study analyzes the complications and the problems developed during and after pedicle screw fixation in patients with spinal disorders and trauma. One hundred twelve patients were treated using the Cotrel-Dubousset pedicle screw fixation system for degenerative disease (57 patients), trauma (42 patients), infection (eight patients), and tumor (five patients) of the lumbar or thoracolumbar spine. The average age of the patients was 47 years and the average followup was 35 months. Forty-seven general complications were seen in 41 patients (36.5%). In addition, hardware failures were observed in 12 patients (10.7%), junctional problems were seen in five patients (4.5%), problems in the instrumented segments were seen in 39 patients (34.7%), and problems of balance occurred in five patients (4.5%). Although the rate of the reported complications was high, the final outcome of the patients was not affected significantly. Placement of the pedicle screws in the thoracolumbar and lumbar spine is a technically demanding procedure. It should be used by experienced and qualified surgeons who are aware of the pitfalls associated with its use.

Lumican expression is positively correlated with the differentiation and negatively with the growth of human osteosarcoma cells

Osteosarcoma is the most common primary bone tumour associated with childhood and adolescence. The possible role of the small leucine‐rich proteoglycan, lumican, in the growth and metastasis of various cancer types has recently been investigated. In this study, the expression of lumican was examined in moderately differentiated (MG‐63) and well‐differentiated (Saos 2) human osteosarcoma cell lines of high and low metastatic capability, respectively. Real‐time PCR, western blotting with antibodies against the protein core and keratan sulfate, and specific enzymatic digestions were the methods employed. The two human osteosarcoma cell lines were found to express and secrete lumican partly substituted with keratan sulfate glycosaminoglycans. Importantly, the non‐metastatic, well‐differentiated Saos 2 cells produced lumican at rates that were up to sevenfold higher than those of highly metastatic MG‐63 cells. The utilization of short interfering RNA specific for the lumican gene resulted in efficient down‐regulation of its mRNA levels in both cell lines. The growth of Saos 2 cells was inhibited by lumican, whereas their migration and chemotactic response to fibronectin were found to be promoted. Lumican expression was negatively correlated with the basal level of Smad 2 activation in these cells, suggesting that lumican may affect the bioavailability of Smad 2 activators. By contrast, these cellular functions of highly aggressive MG‐63 cells were demonstrated not to be sensitive to a decrease in their low endogenous lumican levels. These results suggest that lumican expression may be positively correlated with the differentiation and negatively correlated with the progression of osteosarcoma.

Transforming Growth Factor‐β as a key molecule triggering the expression of versican isoforms v0 and v1, Hyaluronan Synthase‐2 and synthesis of Hyaluronan in Malignant Osteosarcoma cells

Versican, a large sized chondroitin‐sulphate proteoglycan (PG), and its binding partner, hyaluronan (HA), are extracellular matrix (ECM) components that play an essential role in transformed cell behavior. Expression of certain versican isoforms has been implicated in cell migration and proliferation of cancer cells and, on the other hand, disruption of HA synthesis by inhibiting hyaluronan synthase‐2 (HAS2) expression in osteosarcoma cells by suppressing cell proliferation, invasiveness and motility. Considering that growth factors, such as TGF‐β, bFGF and PDGF‐BB, are important regulators for the expression of the ECM macromolecules, in this study we examined the effect of these growth factors on the expression of the various versican isoforms, HA synthases as well as HA synthesis by MG‐63 osteosarcoma cells and normal human osteoblastic periodontal ligament cells (hPDL). Real‐time PCR and metabolic labelling followed by fine HPLC analysis coupled to radiochemical detection were the methods utilized. It was found that, contrary to normal hPDL cells, osteosarcoma MG‐63 cells do not constitutively express the versican isoforms V0 and V1. Exogenous addition of TGF‐β2 stimulated the versican transcript levels mainly by forcing osteosarcoma cells to express V1 and V0 isoforms. PDGF‐BB and bFGF had only minor effects in these cells. In hPDL cells a strong stimulation of the V3 transcript by all growth factors was observed. TGF‐β2 was also the major stimulator of HAS2 isoform expression as well as hyaluronan synthesis in osteosarcoma cells, while PDGF‐BB exerted dominant influence on HAS2 isoform expression and hyaluronan biosynthesis by osteoblasts. The obtained results show for the first time that TGF‐β2 triggers the malignant phenotype pattern of versican and hyaluronan expression in human osteosarcoma cells and indicate that this growth factor may account for the metastatic potential of these cells. IUBMB Life, 58: 47 ‐ 53, 2006

Lateral Mass Screw Complications: Analysis of 1662 Screws

Study Design Retrospective, consecutive patient series. Objective To quantify the risks and the complications associated with screw fixation devices of the cervical spine. Summary of Background Data The usefulness of lateral mass internal fixation has been well documented in the clinical setting. However, there is a paucity of studies examining the complications associated with these devices in a degenerative clinical setting. Methods From 1999 to 2007, 225 consecutive patients underwent posterior cervical fixation using a screw-plate and polyaxial screw-rod implant systems. There were 105 women and 120 men (age range: 45 to 84 y; mean, 68 y). In all patients, the surgical indication was cervical spondylosis with myelopathy. Mean follow-up interval was 18 months (range: 12 to 72 mo). Screw position was evaluated by computed tomography scanning postoperatively in all patients. Clinical and radiographic outcome was assessed at each visit after surgery. Results Intraoperative complications include fracture of lateral mass in 27 screws placement and nerve irritation in 3 bicortical screws. Early complications include hematoma formation in 2 cases and C5 root palsy in 5 cases after spinal canal decompression. Late complications include pseudarthrosis in 6 cases and screw pull-out in 3 cases. There were no cases of spinal cord or vertebral artery injury, infections, deaths, or adjacent segment disease. All patients had radiographic union, and no patient developed mechanical implant failure requiring removal of instrumentation. Reoperation was required in 14 (6.2%) cases because of nerve injury, hematoma formation, pseudarthrosis, and screw pull-out. Conclusions Our clinical findings indicate that lateral mass fixation can be used safely with minimal complications and low rate of morbidity for cervical myelopathy treatment.

Comparison of MR-arthrography and MDCT-arthrography for detection of labral and articular cartilage hip pathology

ObjectiveTo compare the diagnostic ability of MR arthrography (MRa) and MDCT arthrography (CTa) in depicting surgically proven hip labral tears and articular cartilage degradation.Materials and methodsLabral pathology and articular cartilage were prospectively evaluated with MRa and CTa in 14 hips of 10 patients. The findings were evaluated by two independent observers (a musculoskeletal fellow and one senior musculoskeletal radiologist). Sensitivity, specificity, accuracy, and positive predictive value were determined using arthroscopic and open surgery findings as the standard of reference. Interobserver agreement was recorded. All images were assessed for the presence of a labral tear (according to Czerny classification) and for cartilage erosion using a 3 point scale for both methods: 1 = complete visualization-sharp edges, 2 = blurred edges fissuring-partial defects, 3 = exposed bone. The same classification was applied surgically.ResultsDisagreement between the senior observer and the fellow observer was recorded in three cases of labral tearing with MRa and six with CTa. Disagreement was also found in four cases of cartilage erosion with both MRa and CTa. The percent sensitivity, specificity, accuracy, and positive predictive value for correctly assessing the labral tear were as follows for MRa/CTa, respectively: 100/15, 50/13, 90/14, and 90/13 (P < 0.05). The same values for cartilage assessment were 63/66, 33/40, 50/57 and 55/66 (P > 0.05).ConclusionInterobserver reproducibility with MRa is very good for labral tearing assessment. MRa is better for assessing labral tears. CTa shows better, but not statistically significant, demonstration of the articular cartilage.