A Combined Cyto- and Histopathological Diagnostic Approach Reduces Time to Diagnosis and Time to Therapy in First Manifestation of Metastatic Spinal Disease: A Cohort Study.

Malignant spinal lesions (MSLs) are frequently the first manifestation of malignant disease. Spinal care, diagnostic evaluation, and the initiation of systemic therapy are crucial for outcomes in patients (pts) with advanced cancer. However, histopathology (HP) may be time consuming. The additional evaluation of spinal lesions using cytopathology (CP) has the potential to reduce the time to diagnosis (TTD) and time to therapy (TTT). CP and HP specimens from spinal lesions were evaluated in parallel in 61 pts (CP/HP group). Furthermore, 139 pts in whom only HP was performed were analyzed (HP group). We analyzed the TTD of CP and HP within the CP/HP group. Furthermore, we compared the TTD and TTT between the groups. The mean TTD in CP was 1.7 ± 1.7 days (d) and 8.4 ± 3.6 d in HP (p < 0.001). In 13 pts in the CP/HP group (24.1%), specific therapy was initiated based on the CP findings in combination with imaging and biomarker results before completion of HP. The mean TTT in the CP/HP group was 21.0 ± 15.8 d and was significantly shorter compared to the HP group (28.6 ± 23.3 d) (p = 0.034). Concurrent CP for MSLs significantly reduces the TTD and TTT. As a result, incorporating concurrent CP for analyzing spinal lesions suspected of malignancy might have the potential to enhance pts' quality of life and prognosis in advanced cancer. Therefore, we recommend implementing CP as a standard procedure for the evaluation of MSLs.

[Perioperative management after traumatic paraplegia : Avoiding complications]. / Perioperatives Management nach traumatischer Querschnittslähmung : Komplikationen vermeiden.

This article describes the current status of modern treatment options for traumatic spinal cord injuries with a particular focus on the perioperative phase. Along with a recognition of age-related specific features that can impact successful treatment of spinal injuries, prompt interdisciplinary treatment while adhering to the "time is spine" principle is of high importance. By considering this approach and using modern diagnostic and surgical techniques, successful surgical treatment can be achieved while taking into account individual characteristics, such as reduced bone quality, accompanying injuries as well as oncological and inflammatory rheumatic comorbidities. The preventive and treatment strategies for frequently occurring complications in the management of traumatic spinal cord injuries are presented. By considering case-specific factors, utilizing modern surgical techniques, avoiding or promptly treating typical complications and initiating interdisciplinary treatment, crucial groundwork for a successful long-term treatment of this highly debilitating and life-altering injury can be established in the perioperative phase.

Localization and Likelihood of Chondral and Osteochondral Lesions After Patellar Dislocation in Surgically Treated Children and Adolescents.

Background: Patellar dislocation is a common injury in children and adolescents. There is a lack of information about concomitant osteochondral lesions in these patients. Hypothesis: We hypothesized that the likelihood of chondral or osteochondral lesions would increase with each prior patellar dislocation and that the appearance of lesions in surgically treated children and adolescents would be influenced by age, sex, injury mechanism, and body mass index (BMI). Study Design: Case-control study; Level of evidence, 3. Methods: Inclusion criteria were (1) age <18 years, (2) surgical treatment with diagnostic arthroscopy of the knee including description of chondral and osteochondral lesions, and (3) maximum time period between the last patellar dislocation and presentation in our department of 6 weeks and maximum of 4 weeks between presentation and surgery. A total of 153 children (173 knees) with a mean age of 13.0 ± 2.1 years were included. All surgical reports and intraoperative arthroscopic imaging were analyzed retrospectively for the location and severity of lesions. The likelihood of lesions was calculated with multiple stepwise regression models regarding injury mechanism, number of dislocations, sex, age, physeal closure, and BMI. Results: The regression model to predict femoral lesions was statistically significant (χ2[5] = 26.55; P < .001) and identified male sex, BMI ≥25, traumatic injury mechanism, and physeal closure as independent factors associated with the appearance of femoral lesions. The second regression model predicting the appearance of patellar lesions was also statistically significant (χ2[4] = 26.07; P < .001) and identified the traumatic injury mechanism as a single independent predictor for patellar lesions. Conclusion: BMI ≥25, male sex, and physeal closure were factors significantly associated with femoral chondral and osteochondral lesions in our cohort. In case of traumatic lateral patellar dislocation (LPD), the likelihood of patellar and femoral chondral and osteochondral lesions is significantly higher than in nontraumatic LPD. Early magnetic resonance imaging and surgical treatment should be considered in obese patients, male patients, and patients with physeal closure and after traumatic LPD.

Skeletal Status in Patients Scheduled for Elective Lumbar Spine Surgery: Comparison of Discectomy, Decompression, Fusion, and Revision.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To investigate and compare the prevalence of low bone mineral density (BMD) and abnormal laboratory bone metabolism parameters in patients undergoing elective primary discectomy, decompression, and fusion and to outline possible differences in these parameters between patients undergoing revision for skeletal vs non-skeletal complications. METHODS: We retrospectively evaluated BMD measurements by dual-energy x-ray absorptiometry (DXA) in 389 consecutive patients scheduled for elective lumbar spine surgery. Next to demographic characteristics, laboratory bone metabolism parameters were assessed. Group comparisons were performed between primary discectomy, decompression, and fusion. In patients scheduled for revision surgery after fusion, potential differences in the skeletal status between those with skeletal vs non-skeletal complications were analyzed. RESULTS: Osteoporosis by T-score was detected in 6.7%, 11.0% and 14.7% of the patients undergoing discectomy, decompression and fusion, respectively. While vitamin D deficiency (67.6%) and hyperparathyroidism (16.4%) were frequently detected, no differences in laboratory bone metabolism markers could be found between the groups. Female sex (P<.001), higher age (P=.01) and lower BMI (P<.001) were associated with lower BMD. In the cohort of patients undergoing revision surgery due to complications after fusion, those with skeletal complications did not differ in BMD or bone metabolism from those with non-skeletal complications. CONCLUSIONS: Osteoporosis represents a relevant comorbidity in patients scheduled for elective spine surgery, which is why DXA should be routinely performed in these patients. However, DXA may provide limited information in identifying patients at increased risk for skeletal complications after fusion.

Electromagnetic navigation reduces radiation exposure for retrograde drilling in osteochondrosis dissecans of the talus.

BACKGROUND: Retrograde drilling in osteochondrosis dissecans (OCD) is a widely used surgical intervention. A radiation-free electromagnetic navigation system (ENS)-based method was compared with the standard freehand fluoroscopic (SFF) method regarding clinical applicability. METHODS: We performed a clinical cohort study at a department of Orthopaedics in a Level 1 children's hospital with 40 patients (20 SFF and 20 ENS). Retrograde drilling of the talar dome was used in patients with unstable medial OCD (MRI stage 2 according to Hepple's revised classification; stage 2 according to the International Cartilage Repair Society). The outcome measurements were: (a) Intraoperative fluoroscopy exposure and length of surgery and (b) Postoperative serial follow-up MRIs every 6 months. RESULTS: 22 female and 18 male patients aged 13.8 ± 1.6 years (range: 11-17 years) were included. Using the ENS technique, length of surgery was significantly reduced to 20.2 ± 6.4 min compared to 36.1 ± 11.8 min (p < 0.01) for the SFF technique. The average x-ray radiation time for the SFF technique was 23.5 ± 13.5 sec and 1.9 ± 1.7 sec for the ENS technique (p < 0.01). Radiation exposure was significantly reduced from 44.6 ± 19.7 mSv (SFF technique) to 5.6 ± 2.8 mSv (ENS technique) (p < 0.01). Intraoperative perforation of cartilage occurred once in the SFF group. Correct placement of the drilling channel was verified in all patients on follow-up MRI after six months and a timely healing was seen after two years. CONCLUSIONS: The ENS method provides for a significant reduction in length of surgery and radiation exposure. ENS was without intraoperative cartilage perforation. The clinical and radiological follow-up parameters are comparable for SFF- and ENS-guided retrograde drilling. TRIAL REGISTRATION: WF - 085/20, 05/2020 "retrospectively registered" https://www.aerztekammer-hamburg.org/ethik_kommission.html .

Preclinical Quantification of Prostate Cancer-Associated Vascular Alterations in the Bone Microenvironment in vivo.

INTRODUCTION: Prostate cancer has a special predilection to form bone metastases. Despite the known impact of the microvascular network on tumour growth and its dependence on the organ-specific microenvironment, the characteristics of the tumour vasculature in bone remain unknown. METHODS: The cell lines LNCaP, DU145, and PC3 were implanted into the femurs of NSG mice to examine the microvascular properties of prostate cancer in bone. Tumour growth and the functional and morphological alterations of the microvasculature were analysed for 21 days in vivo using a transparent bone chamber and fluorescence microscopy. RESULTS: Vascular density was significantly lower in tumour-bearing bone than in non-tumour-bearing bone, with a marked loss of small vessels. Accelerated blood flow velocity led to increased volumetric blood flow per vessel, but overall perfusion was not affected. All of the prostate cancer cell lines had similar vascular patterns, with more pronounced alterations in rapidly growing tumours. Despite minor differences between the prostate cancer cell lines associated with individual growth behaviours, the same overall pattern was observed and showed strong similarity to that of tumours growing in soft tissue. DISCUSSION: The increase in blood flow velocity could be a specific characteristic of prostate cancer or the bone microenvironment.

The bone microenvironment promotes tumor growth and tissue perfusion compared with striated muscle in a preclinical model of prostate cancer in vivo.

BACKGROUND: Prostate cancer-related morbidity is associated with its preferential spread to the bone. Although the molecular interactions between the bone microenvironment and cancer cells have been researched extensively, the relevance of the microvascular properties of prostate cancer bone metastases remains largely unknown. Most preclinical studies focusing on microvascular analyses are based on heterotopic tumor implantation, whereas the impact of the microenvironment on site-specific growth behavior and angiogenesis is rarely addressed. METHODS: The microvascular changes associated with tumor growth in bone and soft tissue were characterized by implanting single cell suspensions of LnCap, Du145, and Pc3 cells into the femur (femur window) or striated muscle (dorsal skinfold chamber) of NSG mice. Tumor growth and the local microvasculature were analyzed for 21 days using intravital fluorescence microscopy. RESULTS: The results showed a higher engraftment of tumor cells in bone than in striated muscle associated with accelerated growth of LnCap cells and Pc3 cells. Permeability, blood flow, and tissue perfusion rates were greater in bone than in striated muscle. Du145 cells showed similar growth behavior in both tissues with similar vascular properties. The bone microenvironment facilitated tumor engraftment and growth. Increased microvascular density in striated muscle led to a higher tumor burden during early growth, whereas the increased perfusion promoted later prostate cancer growth in bone. CONCLUSIONS: Monitoring prostate cancer microcirculation in bone and soft tissue may be useful to evaluate the organ-specific efficacy of new treatments.

Safety and Efficacy of Single-Stage versus 2-Stage Spinal Fusion via Posterior Instrumentation and Anterior Thoracoscopy: A Retrospective Matched-Pair Cohort Study with 247 Consecutive Patients.

OBJECTIVE: Posterior-anterior spondylodesis is often used to stabilize the spine in various pathologies. The anterior procedure is often performed via thoracoscopy. It is unclear whether the anterior procedure should be performed immediately after posterior instrumentation or after the patient has convalesced. This retrospective study compared perioperative safety and morbidity in 1-stage versus 2-stage posterior-anterior fusion surgery with a thoracoscopic anterior approach. METHODS: All consecutive patients who underwent surgery for posterior-anterior spinal stabilization from 2006 to 2013 were included. American Society of Anesthesiologists score, preoperative and postoperative laboratory values, operation duration, blood loss, intensive care unit stay, pain, postoperative hospital stay, perioperative complications, and preoperative and postoperative Eastern Cooperative Oncology Group and Frankel scores were assessed. A subset of the cohort was selected by propensity score matching to eliminate possible selection bias. RESULTS: There were 247 patients who underwent 1-stage (n = 104) or 2-stage (n = 143) stabilization with thoracoscopic fusion. Spinal pathologies were fracture, malignancy, pyogenic spondylodiscitis, degenerative spinal disorders, and failed previous surgery. One-stage and 2-stage procedures were similar in terms of preoperative, surgical, and postoperative variables, including complication rates, except that the 1-stage procedure was associated with greater pain 2 days after surgery and shorter hospital stay. The propensity score-matched cohort of 64 pairs yielded similar results with only 1-stage patients showing elevated visual analog scale score on postoperative day 2 (3.8 vs. 2.4, P = 0.043). CONCLUSIONS: One-stage stabilization was as safe as 2-stage stabilization and associated with shorter hospitalization. Greater pain after the 1-stage procedure, which resolved 30 days after surgery, reflects the fact that 2-stage patients already had pain relief when they underwent thoracoscopy.

In vivo functional and morphological characterization of bone and striated muscle microcirculation in NSG mice.

Organ-specific microcirculation plays a central role in tumor growth, tumor cell homing, tissue engineering, and wound healing. Mouse models are widely used to study these processes; however, these mouse strains often possess unique microhemodynamic parameters, making it difficult to directly compare experiments. The full functional characterization of bone and striated muscle microcirculatory parameters in non-obese diabetic-severe combined immunodeficiency/y-chain; NOD-Prkds IL2rg (NSG) mice has not yet been reported. Here, we established either a dorsal skinfold chamber or femur window in NSG mice (n = 23), allowing direct analysis of microcirculatory parameters in vivo by intravital fluorescence microscopy at 7, 14, 21, and 28 days after chamber preparation. Organ-specific differences were observed. Bone had a significantly lower vessel density but a higher vessel diameter than striated muscle. Bone also showed higher effective vascular permeability than striated muscle. The centerline velocity values were similar in the femur window and dorsal skinfold chamber, with a higher volumetric blood flow in bone. Interestingly, bone and striated muscle showed similar tissue perfusion rates. Knowledge of physiological microhemodynamic values of bone and striated muscle in NSG mice makes it possible to analyze pathophysiological processes at these anatomic sites, such as tumor growth, tumor metastasis, and tumor microcirculation, as well as the response to therapeutic agents.

Spontaneous Pyogenic Spondylodiscitis in the Thoracic or Lumbar Spine: A Retrospective Cohort Study Comparing the Safety and Efficacy of Minimally Invasive and Open Surgery Over a Nine-Year Period.

PURPOSE: Pyogenic spondylodiscitis is a rare disease, but its incidence is increasing. Over the last decade, spinal surgery has been modified to become minimally invasive. In degenerative spinal disorders, such minimally invasive surgery (MIS) reduces blood loss, muscular trauma, and the hospital stay. However, it is not known whether MIS also confers these benefits to patients with pyogenic spondylodiscitis. This retrospective cohort study compared the safety and efficacy of MIS and the conventional open surgical procedure in patients with pyogenic spondylodiscitis. METHODS: The study cohort consisted of all consecutive patients who underwent surgery for thoracic or lumbar pyogenic spondylodiscitis that was not caused by previous surgery or tuberculosis in our tertiary-care institution between January 2003 and December 2011. RESULTS: Of the 148 eligible patients, 75 and 73 underwent MIS and open surgery, respectively. The 2 groups did not differ in terms of age, body mass index, American Society of Anaesthesiologists score, comorbidities, septic disease, or preoperative neurologic deficit. The 2 methods were associated with similar postoperative stays in the intensive care unit, overall hospital stays, complication rates, and postoperative survival. However, MIS was associated with a significantly shorter operating time, a lower perioperative need for blood products, and, as expected, an increased intraoperative fluoroscopy duration. CONCLUSIONS: Our 9-year experience suggests that MIS is safe and effective for spontaneous pyogenic thoracic and lumbar spondylodiscitis.

Posterior Only Vertebral Column Resection for the Treatment of Severe Spinal Deformities in Pediatric Patients: A Retrospective Case Series.

OBJECTIVE: The treatment of severe spinal deformities in pediatric patients is very challenging. Posterior only vertebral column resection (PVCR) allows for correcting of severe deformities of the vertebral column via a posterior only procedure. We analyzed radiologic outcome of PVCR performed on a series of pediatric patients with severe congenital and acquired spinal deformities. METHODS: A case series of 11 pediatric patients with severe spinal deformity who were treated by PVCR between 2009 and 2013 were retrospectively analyzed. All patients had posterior instrumentation and reconstruction of the anterior column with titanium cages filled with autologous bone. Seven patients had pure kyphosis or kyphoscoliosis, whereas 4 patients were treated because of scoliotic deformities. The patient records were reviewed for demographic and general clinical data. Complications and adverse events, transfusion rates, and surgical time were recorded. Radiologic analysis included Cobb angles and percentage of correction, analysis of sagittal profile, time to fusion, and possible complications related to instrumentation. RESULTS: Average preoperative scoliosis of 61° was corrected to 32°, resulting in a 50% correction at final follow-up. Coronal imbalance was improved to 36% at the most recent follow-up. Mean preoperative kyphotic deformity was 90° and was corrected to 43° at the last follow-up evaluation. Intraoperative complications included loss of the neuromonitoring signals in 2 cases and pleural laceration in 1 case. CONCLUSIONS: PVCR for children is an effective and safe technique providing a successful correction of complex pediatric spinal deformities. Nevertheless, it remains a technically highly demanding procedure, implying the possibility of severe complications.

Prospective evaluation of the Eppendorf-Cologne Scale.

OBJECTIVES: Early diagnosis of traumatic brain injury and reliable prediction of outcome are essential for determining treatment strategies and allocating resources. This study re-evaluates the Eppendorf-Cologne Scale (ECS) and its predictive accuracy for outcome compared with the Glasgow Coma Scale (GCS). METHODS: A prospective cohort analysis of severely injured trauma patients registered in the Trauma Registry of the German Society for Trauma Surgery from 2012-2013 was carried out. Only directly admitted patients alive on admission with complete data on GCS, ECS and outcome in terms of survival to hospital discharge or death were included. The predictive accuracy in terms of the outcome of the ECS and the GCS was modelled using area under the receiver operating characteristic (AUROC) curve analysis. RESULTS: A total of 17 616 patients fulfilled the study inclusion criteria. The ECS outmatched the predictive accuracy of the GCS for outcome (AUROC, 0.853, 95% confidence interval, 0.831-0.854; and AUROC 0.836; 95% confidence interval, 0.825-0.848, respectively; P=0.062). An ECS score of 8 was associated with a 25-fold higher mortality compared with an ECS score of 0. Patients who had an ECS score of 8 had a 1.5-fold higher mortality compared with patients allocated a GCS score of 3. CONCLUSION: The ECS shows a higher accuracy for prediction of outcome compared with the GCS and enables further differentiation within the critical GCS 3 collective.

Sunitinib treatment reduces tumor growth and limits changes in microvascular properties after minor surgical intervention in an in vivo model of secondary breast cancer growth in bone.

BACKGROUND AND OBJECTIVES: Surgical interventions can alter the balance between pro- and anti-angiogenic growth factors and thereby modulate tumor growth. Since the microcirculatory properties of tumors underlie organ-specific differences, the microhemodynamic characteristics of bone metastasis have not yet been fully described. Angiogenesis inhibitors are increasingly being used to treat advanced stages of cancer. We hypothesized that the anti-angiogenic drug sunitinib abrogates alterations in microvascular properties following a minor surgical intervention in an in vivo model of secondary breast cancer growth in the bone. METHODS: Intravital microscopy was performed over 25 days using a xenograft model of breast cancer tumor growth in the bone to determine changes in microvascular properties during sunitinib treatment. Mastectomy was performed on day 5 to evaluate the effect of a minor surgical trauma on tumor growth and microvascular properties. RESULTS: Anti-angiogenic therapy resulted in reduced tumor growth, decreased vascular density, and increased vascular diameters. Blood flow velocity remained constant while microvascular permeability temporarily increased after the surgical intervention. CONCLUSIONS: Administration of sunitinib reduced tumor growth and altered microcirculatory properties in a time-dependent manner. The observed dramatic increase in microvascular permeability after the surgical intervention may have implications for local tumor growth, and metastatic dissemination. J. Surg. Oncol. 2016;113:515-521. © 2016 Wiley Periodicals, Inc.

A novel computer navigation system for retrograde drilling of osteochondral lesions.

Osteochondritis dissecans (OCD) represents an important clinical entity in orthopedic sports medicine. Once surgical intervention is required, retrograde drilling for OCD lesions remains technically challenging. A novel electromagnetic navigation system was developed to be a radiation-free navigation tool providing spatiotemporal real-time information to the surgeon without the need for a stationary patient tracker and without relevant setup and calibration times. The novel system was tested for arthroscopically assisted retrograde drilling of cadaveric OCD lesions of the knee and talus and compared with the gold standard fluoroscopy-guided retrograde drilling procedure in a controlled laboratory study setup. The novel method considerably improves on the standard operating procedure in terms of safety, operation time, and radiation exposure and will be available for further surgical indications.

Accuracy analysis of a novel electromagnetic navigation procedure versus a standard minimally invasive method for arthroscopically assisted acromioclavicular joint reconstructions.

PURPOSE: The aim of this cadaveric study was to evaluate the accuracy, feasibility, and operation time of a novel electromagnetic navigation system (ENS) and procedure for transclavicular-transcoracoid tunnel placement compared with a standard minimally invasive (SMI) reconstruction method for minimally invasive arthroscopically assisted anatomic acromioclavicular joint reconstruction. METHODS: Ten arthroscopically assisted electromagnetic-navigated transclavicular-transcoracoid drilling procedures and 10 SMI procedures were performed on 10 human cadavers using 2 TightRope reconstructions (Arthrex, Naples, FL) for each site. Postoperative computed tomography scans were acquired to determine tunnel placement accuracy. Optimal coracoid tunnel placement was defined according to the anatomic insertions of the trapezoid and conoid ligaments with the oblong button placed in a center-base position at the coracoid undersurface without cortical breach or fracture. Both reconstruction procedures were performed without fluoroscopy. RESULTS: Successful tunnel placement was accomplished in 98.8% using the ENS method and in 83.8% using the SMI procedure (P = .087). The mean overall operation time was 28.5 ± 6.6 minutes for the ENS method and 35.2 ± 3.9 minutes for the SMI method (P = .012). The ENS procedure required no directional readjustments or restarts. Drill misguidance with subsequent cortical breach occurred twice in the SMI group. In both groups no fractures were documented. CONCLUSIONS: In this descriptive laboratory study, both the ENS and the SMI techniques achieved the desired anatomic reconstruction. Compared with the SMI method, the ENS procedure showed higher accuracy, required a shorter operation time, and was associated with no complications. CLINICAL RELEVANCE: Length of surgery, drilling accuracy, and reduction of radiation exposure in acromioclavicular joint reconstruction procedures affect the safety of both patients and surgeons.

Electromagnetic navigation provides high accuracy for transcoracoid-transclavicular drilling.

PURPOSE: A novel radiation-free electromagnetic navigation system (ENS)-based method was developed, and its feasibility and accuracy for transclavicular-transcoracoid drilling procedures were evaluated in an experimental setting. METHODS: Sixteen arthroscopically assisted electromagnetic navigated transcoracoid-transclavicular drilling procedures with subsequent TightRope device implantation were performed on eight human cadavers. Post-operative fluoroscopy and CT-scan analysis were acquired to determine tunnel placement accuracy. Optimal tunnel placement was defined as both the coracoid entry and exit point of the tunnel localized in the centre position of the coracoid base without cortical breach or fracture. RESULTS: Successful tunnel placement was accomplished in all 16 cases. The mean overall operation time was 30.3 ± 5.0 min. Regarding the coracoid exit point, 15 of 16 tunnels (93.8%) were localized in the desired base-centre position. During the navigated drilling procedure, no misguidance of the drill requiring directional readjustments or restarts occurred. No cortical breach, no fractures and no complications occurred. CONCLUSIONS: The electromagnetically navigated transcoracoid-transclavicular drilling procedure used in this study demonstrated high targeting accuracy, required no intraoperative radiographs, was associated with no complications and provided user-friendliness.

Chemokine profile of disc degeneration with acute or chronic pain.

OBJECT: Disc-related disorders such as herniation and chronic degenerative disc disease (DDD) are often accompanied by acute or chronic pain. Different mediators have been identified in the development of radicular pain and DDD. Previous studies have not analyzed individual cytokine profiles discriminating between acute sciatic and chronic painful conditions, nor have they distinguished between different anatomical locations within the disc. The aim of this study was to elucidate the protein biochemical mechanisms in DDD. METHODS: The authors determined expression levels of matrix metalloproteinase-3, transforming growth factor-ß (TGF-ß), tumor necrosis factor-α, interleukin-1α, and pro-substance P using enzyme-linked immunosorbent assay and Western blot analyses in patients suffering from DDD (n = 7), acute back pain due to herniated discs with radiculopathy (n = 7), and a control group (n = 7). Disc tissue samples from the anulus fibrosus (AF) and nucleus pulposus (NP) were analyzed. Statistical analysis was performed using nonparametric tests. RESULTS: A distinct distribution of cytokines was found in different anatomical regions of intervertebral discs in patients with DDD and herniated NP. Increased TGF-ß levels were predominantly found in DDD. Matrix metalloproteinase-3 was increased in acute herniated disc material. Increased levels of substance P were found in patients suffering from DDD but not in patients with disc herniation. The data showed significantly higher levels of proinflammatory cytokines in the AF and NP of patients with DDD, and the expression levels in the AF were even higher than in the NP, suggesting that the inflammatory response initiates from the AF. CONCLUSIONS: These results highlight the complex mechanisms involved during disc degeneration and the need to distinguish between acute and chronic processes as well as different anatomical regions, namely the AF and NP. They also highlight potential problems in disc nucleus replacement therapies because the results suggest a biochemical link between AF and NP cytokine expression.

Angiogenic growth factors in rheumatoid arthritis.

We investigated whether the angiogenic profile, which is based on the local expression and systemic levels of angiogenic growth factors (VEGF, Ang-1, Ang-2, and the corresponding receptors), differs between rheumatoid arthritis (RA) and osteoarthritis (OA) patients. We determined the expression of VEGF, Ang-1, and Ang-2 together with its receptors (VEGFR-1/-2 and Tie2) in synovium tissue (ST) and muscular tissue (MT) from patients with RA and OA using quantitative PCR. Tissue samples were obtained from 15 RA and 19 OA patients during total knee arthroplasty. Control MT samples (n = 10) were obtained during spinal surgery. Results are correlated to VEGF and angiopoietin serum levels via ELISA measurements. The VEGF expressions in ST and serum levels were significantly higher in RA patients than in OA patients (P < 0.05). Furthermore, the VEGFR-1 and VEGFR-2 expression in ST from RA patients were significantly higher than in OA patients (P < 0.001 and P < 0.05). The relative concentration of angiopoietins (Ang-1/Ang-2 ratio) was significantly increased in RA (P < 0.01). Serum levels for Ang-2 showed no significant differences. Statistical analysis showed a significant higher level of Tie2 in RA patients (P < 0.001). Analysis of local levels of VEGF, VEGFR-1, VEGFR-2, Ang-1, Ang-2, and Tie2 in the muscular tissue showed no significant difference between RA and OA patients. These results underline the importance of pro-angiogenic growth factor levels for RA corroborating the assumption that VEGF and angiopoietins play an important role in the pathogenesis of RA.

Percutaneous instrumentation of the cervical and cervico-thoracic spine using pedicle screws: preliminary clinical results and analysis of accuracy.

The pedicle screw instrumentation represents the most rigid construct of the cervical and cervicothoracic spine and in spite of the risks to neurovascular structures clinical relevant complications do not occur frequently. The steep angles of the cervical pedicles result in a wide surgical exposure with extensive muscular trauma. The objective of this study was the evaluation of the accuracy of cervical pedicle screw insertion through a minimally invasive technique to reduce access-related muscular trauma. Therefore, percutaneous transpedicular instrumentation of the cervical and cervicothoracic spine was performed in 15 patients using fluoroscopy. All instrumentations from C2 to Th4 were inserted bilaterally through 2 to 3-cm skin and fascia incisions even in multilevel procedures and the rods were placed by blunt insertion through the incision. Thin-cut CT scan was used postoperatively to analyze pedicle violations. 76.4% of 72 screws were placed accurately. Most pedicle perforations were seen laterally towards the vertebral artery. Critical breaches >2 mm or narrowing of the transversal foramen occurred in 12.5% of screws; however, no revision surgery for screw displacement was needed in the absence of clinical symptoms. No conversion from percutaneous to open surgery was necessary. It was concluded that percutaneous transpedicular instrumentation of the cervical spine is a surgically demanding technique and should be reserved for experienced spine surgeons. The indications are limited to instrumentation-only procedures or in combination with anterior treatment, but with the potential to minimize access-related morbidity.

Primary tumor dependent inhibition of tumor growth, angiogenesis, and perfusion of secondary breast cancer in bone.

The systemic balance of angiogenic and anti-angiogenic factors has been proposed to play a key-role in primary tumor growth dependent growth suppression of secondary tumors. Despite the importance of the organ microenvironment to angiogenesis and microcirculation, the influence of a primary tumor on secondary bone tumors has not been investigated so far. Since breast cancer has a high propensity to spread to bone, we used an in vivo xenograft model to determine the impact of growing breast cancer cells (MCF-7) in the mammary fat pad on the microvascular properties of subsequently inoculated secondary breast cancer tumors in bone. Mice were either treated with a resection of the primary tumor (n = 10) or no surgery (n = 9) and intravital microscopy was performed over 25 days in bone tumors. Tumor growth in bone was temporarily suppressed by the primary tumor on days 10 and 14. While microvascular permeability and vascular diameter decreased in both groups over time, the presence of the primary tumor was accompanied by a decreased tumor perfusion on days 8 and 10 through a reduction in vessels with diameters between 5 and 20 µm. The results imply a potential benefit of a therapeutic regime in which the resection of the primary tumor is combined with an anti-angiogenic therapy in the perioperative or direct postoperative period. This might result in reduced progression of bone metastasis subsequent to excision of the primary tumor.