Analysis of Three-Dimensional Bone Microarchitecture of the Axis Exposes Pronounced Regional Heterogeneity Associated with Clinical Fracture Patterns.

The odontoid process (dens) of the second cervical vertebra (axis) is prone to fracture. While the importance of its skeletal integrity has been previously noted, representative three-dimensional microarchitecture analyses in humans are not available. This study aimed to determine the bone microarchitecture of the axis using high-resolution quantitative computed tomography (HR-pQCT) and to derive clinical implications for the occurrence and treatment of axis fractures. For initial clinical reference, the apparent density of the axis was determined based on clinical computed tomography (CT) images in patients without and with fractures of the axis. Subsequently, 28 human axes (female 50%) obtained at autopsy were analyzed by HR-pQCT. Analyses were performed in three different regions corresponding to zones I (tip of dens), II (base of dens), and III (corpus axis) of the Anderson and D'Alonzo classification. Lower apparent densities based on clinical CT data were detected in zone II and III compared to zone I in both the group without and with fracture. In the autopsy specimens, cortical thickness and bone volume fraction decreased continuously from zone I to zone III. Trabecular and cortical tissue mineral density was lowest in zone III, with no differences between zones I and II. In conclusion, our clinical and high-resolution ex vivo imaging data highlight a marked regional heterogeneity of bone microarchitecture, with poor cortical and trabecular properties near the dens base. These results may partly explain why zones II and III are at high risk of fracture and osteosynthesis failure.

Spontaneous spondylodiscitis and endocarditis: interdisciplinary experience from a tertiary institutional case series and proposal of a treatment algorithm.

Previously, the simultaneous presence of endocarditis (IE) has been reported in 3-30% of spondylodiscitis cases. The specific implications on therapy and outcome of a simultaneous presence of both diseases are not yet fully evaluated. Therefore, the aim of this study was to investigate the influence of a simultaneously present endocarditis on the course of therapy and outcome of spondylodiscitis. A prospective database analysis of 328 patients diagnosed with spontaneous spondylodiscitis (S) using statistical analysis with propensity score matching was conducted. Thirty-six patients (11.0%) were diagnosed with concurrent endocarditis (SIE) by means of transoesophageal echocardiography. In our cohort, the average age was 65.82 ± 4.12 years and 64.9% of patients were male. The incidence of prior cardiac or renal disease was significantly higher in the SIE group (coronary heart disease SIE n = 13/36 vs. S n = 57/292, p < 0.05 and chronic heart failure n = 11/36 vs. S n = 41/292, p < 0.05, chronic renal failure SIE n = 14/36 vs. S n = 55/292, p < 0.05). Complex interdisciplinary coordination and diagnostics lead to a significant delay in surgical intervention (S = 4.5 ± 4.5 days vs. SIE = 8.9 ± 9.5 days, p < 0.05). Mortality did not show statistically significant differences: S (13.4%) and SIE (19.1%). Time to diagnosis and treatment is a key to efficient treatment and patient safety. In order to counteract delayed therapy, we developed a novel therapy algorithm based on the analysis of treatment processes of the SIE group. We propose a clear therapy pathway to avoid frequently observed pitfalls and delays in diagnosis to improve patient care and outcome.

Outcome after Posterior Vertebral Column Resection in Patients with Severe Osteoporotic Fractures-A Retrospective Analysis from Two Centers.

Background and Objectives: In osteoporotic fractures of the spine with resulting kyphosis and threatening compression of neural structures, therapeutic decisions are difficult. The posterior vertebral column resection (pVCR) has been described by different authors as a surgical treatment in a single-stage posterior procedure. The aim of this study is to evaluate midterm outcomes of patients treated by pVCR due to severe osteoporotic fractures. Materials and Methods: Retrospective data analysis of all the patients treated for osteoporotic fractures by pVCR from 2012-2020 at two centers was performed. Demographic data, visual analog scale (VAS), Frankel scale (FS), Karnofsky performance status (KPS), radiological result and spinal fusion rates were evaluated. Results: A total of 17 patients were included. The mean age was 70 ± 10.2 y. The mean VAS decreased significantly from 7.7 ± 2.8 preoperatively to 3.0 ± 1.6 at last follow-up (p < 0.001) and the segmental kyphosis decreased from 29.4 ± 14.1° to 7.9 ± 8.0° (p < 0.001). The neurologic function on the FS did not worsen in any and improved in four of the patients. The median KPS remained stable over the whole observation period (70% vs. 70%). Spinal fusion was observed in nine out of nine patients who received CT follow-up >120 days after index surgery. Conclusions: This study showed that pVCR is a safe surgical technique with few surgical complications and no neurological deterioration considering the cohort. The patients' segmental kyphosis and VAS improved significantly, while the KPS remained stable.

Influence of microbiological diagnosis on the clinical course of spondylodiscitis.

PURPOSE: This study sought to recognize differences in clinical disease manifestations of spondylodiscitis depending on the causative bacterial species. METHODS: We performed an evaluation of all spondylodiscitis cases in our clinic from 2013-2018. 211 patients were included, in whom a causative bacterial pathogen was identified in 80.6% (170/211). We collected the following data; disease complications, comorbidities, laboratory parameters, abscess occurrence, localization of the infection (cervical, thoracic, lumbar, disseminated), length of hospital stay and 30-day mortality rates depending on the causative bacterial species. Differences between bacterial detection in blood culture and intraoperative samples were also recorded. RESULTS: The detection rate of bacterial pathogens through intraoperative sampling was 66.3% and could be increased by the results of the blood cultures to a total of 80.6% (n = 170/211). S. aureus was the most frequently detected pathogen in blood culture and intraoperative specimens and and was isolated in a higher percentage cervically than in other locations of the spine. Bacteremic S. aureus infections were associated with an increased mortality (31.4% vs. overall mortality of 13.7%, p = 0.001), more frequently developing complications, such as shock, pneumonia, and myocardial infarction. Comorbidities, abscesses, length of stay, sex, and laboratory parameters all showed no differences depending on the bacterial species. CONCLUSION: Blood culture significantly improved the diagnostic yield, thus underscoring the need for a structured diagnostic approach. MSSA spondylodiscitis was associated with increased mortality and a higher incidence of complications.

Cortical threaded pedicle screw improves fatigue strength in decreased bone quality.

PURPOSE: Inadequate anchoring of pedicle screws in vertebrae with poor bone quality is a major problem in spine surgery. The aim was to evaluate whether a modified thread in the area of the pedicle could significantly improve the pedicle screw fatigue strength. METHODS: Fourteen human cadaveric vertebral bodies (L2 and L3) were used for in vitro testing. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by standard pedicle screws with a constant double thread on the right pedicle and a partial doubling of the threads-quad thread-(cortical thread) in the area of the pedicle on the left pedicle. Pulsating sinusoidal, cyclic load (0.5 Hz) with increasing peak force (100 N + 0.1 N/cycles) was applied orthogonal to the screw axis. The baseline force remained constant (50 N). Fatigue test was terminated after exceeding 5.4-mm head displacement (~ 20° screw tilting). RESULTS: The mean fatigue load at failure was 264.9 N (1682 cycles) for the standard screws and was increased significantly to 324.7 N (2285 cycles) by the use of cortical threaded screws (p = 0.014). This effect is particularly evident in reduced BMD (standard thread 241.2 N vs. cortical thread 328.4 N; p = 0.016), whereas in the group of vertebrae with normal BMD no significant difference could be detected (standard thread 296.5 N vs. cortical thread 319.8 N; p = 0.463). CONCLUSIONS: Compared to a conventional pedicle screw, the use of a cortical threaded pedicle screw promises superior fatigue load in vertebrae with reduced bone quality.

Posterior vertebral column resection as a safe procedure leading to solid bone fusion in metastatic epidural spinal cord compression.

OBJECTIVE: Cancer is one of the leading causes of death and greatly decreases a patient's quality of life. Vertebral metastases often lead to epidural spinal cord compression (ESCC) requiring surgical therapy. It has previously been shown that in patients with metastatic ESCC (MESCC), a surgical intervention leads to an improved outcome. Although the treatment paradigms in spinal metastases have changed and separation surgery followed by stereotactic radiosurgery is considered the best strategy, there are still cases in which 360° decompression with stabilization is indicated. In these patients, a proper bone fusion should be the treatment goal to guarantee good clinical results in extended survival times through progressions in oncological therapies. The aim of this study was to examine the safety and feasibility of posterior vertebral column resection (pVCR) in everyday clinical practice, achievement of bone fusion, and midterm outcome in patients with MESCC. METHODS: All patients treated with pVCR due to MESCC between 2013 and 2020 were enrolled in this observational single-center study. Demographics, outcome parameters, numeric rating scale (NRS) score, Frankel grade, and Karnofsky Performance Scale (KPS) score were evaluated. Radiological images routinely acquired during follow-up were reviewed and screened for the presence of bone fusion. RESULTS: Sixty-six patients were treated by eight surgeons. The mean follow-up period was 549 ± 739 days. At baseline, the average age was 64.4 ± 10.9 years. Reported NRS scores (preoperative 6.2 ± 1.7 vs postoperative 3.4 ± 1.6) and segmental kyphosis as measured on sagittal CT images (preoperative 13.5° ± 8.6° vs postoperative 3.8° ± 5.4°) decreased significantly (p < 0.001). In only 2 patients (3%), the Frankel grade worsened postoperatively, whereas in 12 patients (18.2%) an improvement was documented. The KPS score remained constant during the observation period (preoperative 73.2% ± 18.2% vs 78.3% ± 18% at last follow-up). Bone fusion was observed in 26 patients (86.7%) receiving CT more than 100 days after the index surgery. CONCLUSIONS: pVCR is a reliable surgical technique in daily clinical practice, which proves to be beneficial in terms of short- as well as midterm outcome, as judged by the KPS and NRS. The overall improvement in the Frankel grade shows patient safety. A bone fusion was observed regularly in oncological patients undergoing pVCR. The authors therefore conclude that pVCR is a safe, fast, and efficient strategy to achieve stability and pain relief by achievement of bone fusion in cancer patients.

Intraoperative blood loss in oncological spine surgery.

OBJECTIVE: Intraoperative blood loss in patients undergoing oncological spine surgery poses a major challenge for vulnerable patients. The goal of this study was to assess how the surgical procedure, tumor type, and tumor anatomy, as well as anesthesiological parameters, affect intraoperative blood loss in oncological spine surgery and to use this information to generate a short preoperative checklist for spine surgeons and anesthesiologists to identify patients at risk for increased intraoperative blood loss. METHODS: The authors performed a retrospective analysis of 430 oncological patients who underwent spine surgery between 2013 and 2018 at the university medical spine center. Enrolled patients had metastatic tumor of the spine requiring surgical decompression of neural structures and/or stabilization including tumor biopsy using an open, percutaneous, and/or combined dorsoventral approach. Patients requiring vertebro- and kyphoplasty or biopsy only were excluded. Statistical analyses performed included a multiple linear regression analysis. RESULTS: The mean intraoperative blood loss in the study patient cohort was 1176 ± 1209 ml. In total, 33.8% of patients received intraoperative red blood cell transfusions. The statistical analyses showed that tumor histology indicating myeloma, operative procedure length, epidural spinal cord compression (ESCC) score, tumor localization, BMI, and surgical strategy were significantly associated with increased intraoperative blood loss or risk of needing allogeneic blood transfusions. Anesthesiological parameters such as the American Society of Anesthesiologists (ASA) Physical Status classification score were not associated with blood loss. Multiple linear regression analysis demonstrated good predictive value (r = 0.437) for a five-item preoperative checklist to identify patients at risk for high intraoperative blood loss. CONCLUSIONS: The analyses performed in this study demonstrated key factors affecting intraoperative blood loss and showed that a simple preoperative checklist including these factors can be used to identify patients undergoing surgery for metastatic spine tumors who are at risk for increased intraoperative blood loss. ABBREVIATIONS: ABT = allogeneic blood transfusion; ASA = American Society of Anesthesiologists; ESCC = epidural spinal cord compression; KW = Kruskal-Wallis; MET = metabolic equivalent of task; RBC = red blood cell.

Reduced cement volume does not affect screw stability in augmented pedicle screws.

PURPOSE: Cement augmentation of pedicle screws is able to improve screw anchorage in osteoporotic vertebrae but is associated with a high complication rate. The goal of this study was to evaluate the impact of different cement volumes on pedicle screw fatigue strength. METHODS: Twenty-five human vertebral bodies (T12-L4) were collected from donors between 73 and 97 years of age. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by conventional pedicle screws, and unilateral cement augmentation was performed. Thirteen vertebrae were augmented with a volume of 1 ml and twelve with a volume of 3 ml bone cement. A fatigue test was performed using a cranial-caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force (100 N + 0.1 N/cycles). RESULTS: The load to failure was 183.8 N for the non-augmented screws and was increased significantly to 268.1 N (p < 0.001) by cement augmentation. Augmentation with 1 ml bone cement increased the fatigue load by 41% while augmentation with 3 ml increased the failure load by 51% compared to the non-augmented screws, but there was no significant difference in fatigue loads between the specimens with screws augmented with 1 ml and screws augmented with 3 ml of bone cement (p = 0.504). CONCLUSION: Cement augmentation significantly increases pedicle screw stability. The benefit of augmentation on screw anchorage was not significantly affected by reducing the applied volume of cement from 3 ml to 1 ml. Considering the high risk of cement leakage during augmentation, we recommend the usage of a reduced volume of 1 ml bone cement for each pedicle screw. These slides can be retrieved under Electronic Supplementary Material .

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.

Posterior vertebral column resection with 360-degree osteosynthesis in osteoporotic kyphotic deformity and spinal cord compression.

Osteoporotic fractures with severe kyphosis and neurologic deficits often require decompression and stabilisation. To reduce the risk of procedure-related complications, single-stage posterolateral vertebrectomy and a 360-degree fusion can be performed. An adequate reduction of kyphotic deformity through this approach has not been reported. The aim of this study is to investigate the efficacy of kyphotic deformity reduction by this approach in osteoporotic situation. A retrospective analysis and chart review was performed for 10 consecutive patients who underwent posterolateral decompression and posterior vertebrectomy with dorsal mesh stabilisation and reduction of kyphotic deformity. Preoperative back pain was 8.6 on a visual analogue scale; it was reduced to 5.5 at discharge and 3.7 at the latest follow-up (18 months). The Frankel score improved from D to E (three patients) or was equal (E). Radiological segmental kyphosis was corrected from a mean of 25° to 5° (p < 0.008) postoperatively with a loss of 3° at follow-up (p < 0.005). Single-stage posterolateral vertebrectomy allow for a fast and safe reconstitution/preservation of neurological function in patients with osteoporotic fracture and kyphotic deformity. A significant correction of often-accompanied hyperkyphosis is possible without neurological deterioration and with an improved sagittal profile and good pain reduction.

Time to augment?! Impact of cement augmentation on pedicle screw fixation strength depending on bone mineral density.

PURPOSE: Cement augmentation of pedicle screws is known to increase their mechanical strength. Aim was to evaluate the impact of cement augmentation on pedicle screw fatigue strength in dependence of the bone mineral density (BMD). METHODS: Twenty-one human L2 vertebral bodies from donors between 19 and 96 years of age were used for in vitro experiments. BMD was measured using quantitative computed tomography (QCT). Two pedicle screws were inserted in each specimen and unilaterally augmented with bone cement. Fatigue testing was performed using a cranio-caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force (100 N + 0.1 N/cycles). Results were evaluated for the BMD groups: normal: BMD > 120 mg/cm3, osteopenic: BMD 80-120 mg/cm3, and osteoporotic: BMD < 80 mg/cm3 bone mass. RESULTS: There was a significant correlation between fatigue force and BMD for the non-augmented and augmented screws (non-augmented R2 = 0.839, p < 0.001; augmented R2 = 0.551, p < 0.001). There was a significantly increased fatigue strength of the augmented screws over the non-augmented screws in the osteoporotic group (p = 0.001), while the differences in the other groups were not significant (normal p = 0.818/osteopenic p = 0.132). CONCLUSIONS: The benefit of pedicle screw cement augmentation significantly depends on the bone mineral density and has the greatest extent of increased fatigue strength in osteoporotic vertebrae. Preoperative measurement of the BMD is strongly recommended to predict the benefit of augmentation and reinforce the decision for cement augmentation. These slides can be retrieved under Electronic Supplementary Material.

Reducing kyphotic deformity by posterior vertebral column resection with 360° osteosynthesis in metastatic epidural spinal cord compression (MESCC).

PURPOSE: Metastatic epidural spinal cord compression (MESCC) often requires anterior-posterior decompression and stabilization. To reduce approach-related complications, single-stage posterolateral vertebrectomy and 360° fusion is often performed. However, a sufficient reduction of kyphotic deformity through this approach has not been reported. The purpose of this study is to investigate the efficacy of kyphotic deformity reduction by this approach in MESCC. METHODS: A retrospective analysis and chart review was performed for 14 consecutive patients who underwent a vertebrectomy and decompression from a posterolateral approach. Anterior mesh stabilization of the ventral column is used as hypomochlion for the posterior compression manoeuvre, which leads to reduction of the kyphotic deformity. RESULTS: Pre-operative back pain was 7.2 on a visual analogue scale. Back pain was reduced to 4.4 at discharge and 2.0 at the latest follow-up with a mean follow-up of 12 months (p < 0.001). The Frankel score remains constant or improved from D to E. Radiological segmental kyphosis was corrected from a mean of 16° to 4° (p < 0.001) post-operatively with a loss of 3° at the final follow-up, but still with significant corrections compared with the pre-operative measurements (p < 0.003). CONCLUSION: Single-stage posterolateral vertebrectomy and reconstruction is a safe and less invasive approach that allows a sufficient reduction of hyperkyphosis and preservation of neurological function in patients with MESCC. This approach is an efficient alternative to anterior-posterior fusion with good pain reduction and improved sagittal profile.

Insufficient stability of pedicle screws in osteoporotic vertebrae: biomechanical correlation of bone mineral density and pedicle screw fixation strength.

PURPOSE: Loosening of pedicle screws is one major complication of posterior spinal stabilisation, especially in the patients with osteoporosis. Augmentation of pedicle screws with cement or lengthening of the instrumentation is widely used to improve implant stability in these patients. However, it is still unclear from which value of bone mineral density (BMD) the stability of pedicle screws is insufficient and an additional stabilisation should be performed. The aim of this study was to investigate the correlation of bone mineral density and pedicle screw fatigue strength as well as to define a threshold value for BMD below which an additional stabilisation is recommended. METHODS: Twenty-one human T12 vertebral bodies were collected from donors between 19 and 96 years of age and the BMD was measured using quantitative computed tomography. Each vertebral body was instrumented with one pedicle screw and mounted in a servo-hydraulic testing machine. Fatigue testing was performed by implementing a cranio-caudal sinusoidal, cyclic (0.5 Hz) load with stepwise increasing peak force. RESULTS: A significant correlation between BMD and cycles to failure (r = 0.862, r 2 = 0.743, p < 0.001) as well as for the linearly related fatigue load was found. Specimens with BMD below 80 mg/cm3 only reached 45% of the cycles to failure and only 60% of the fatigue load compared to the specimens with adequate bone quality (BMD > 120 mg/cm3). CONCLUSIONS: There is a close correlation between BMD and pedicle screw stability. If the BMD of the thoracolumbar spine is less than 80 mg/cm3, stability of pedicle screws might be insufficient and an additional stabilisation should be considered.

Cervical vertebroplasty for osteolytic metastases as a minimally invasive therapeutic option in oncological surgery: outcome in 14 cases.

OBJECTIVE The treatment of cervical spinal metastases represents a controversial issue regarding the type, extent, and invasiveness of interventions. In the lumbar and thoracic spine, kypho- and vertebroplasties have been established as minimally invasive procedures for patients with metastases to the vertebral bodies and without neurological deficit. These procedures show good results with respect to pain reduction and low complication rates. However, limited data are available for kypho- and vertebroplasties for cervical spinal metastases. In an effort to add to existing data, the authors here present a case series of 14 patients who were treated for osteolytic metastases of the cervical spine using vertebroplasty alone or in addition to another surgical procedure involving the cervical spine in a palliative setting to reduce pain and restore stability. METHODS Fourteen patients consisting of 8 males and 6 females, with a mean age of 64.7 years (range 44-85 years), were treated with vertebroplasty at the authors' clinic between January 2015 and November 2016. In total, 25 vertebrae were treated with vertebroplasty: 10 C-2, 5 C-3, 2 C-4, 2 C-5, 3 C-6, and 3 C-7. Two patients had an additional posterior stabilization and 5 patients an additional anterior stabilization. In 13 cases, the surgical approach was a modified Smith-Robinson approach; in 1 case, the cement was injected into the corpus axis from posteriorly. Patients with osteolytic defects of the posterior wall of the vertebral body did not undergo surgery, nor did patients with neurological deficits. Preoperatively, on the 2nd day after surgery, and at the follow-up, neck pain was rated using the visual analog scale (VAS). RESULTS Twelve patients were examined at follow-up (mean 9 months). Neck pain was rated as a mean of 6.0 (range 3-8) preoperatively, 2.9 on Day 2 after surgery (range 0-5), and 0.5 at the follow-up (range 0-4), according to the VAS. The mean Neck Disability Index at follow-up was 3.6% (range 0%-18%). CONCLUSIONS Anterior vertebroplasty of the cervical spine via an anterolateral approach represents a safe and minimally invasive procedure with a low complication rate and appears suitable for reducing pain and restoring stability in cases of cervical spinal metastases. Vertebroplasties can be combined with other anterior and posterior operations of the cervical spine and, in the axis vertebra, can be performed transpedicularly from posteriorly. Thus, in cases in which the posterior wall of the vertebral body is intact, vertebroplasty represents a less invasive alternative to vertebral replacement in oncological surgery. Prospective randomized trials with a longer follow-up period and a larger patient cohort are needed to confirm the encouraging results of this case series.

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.

Retrospective feasibility analysis of modified posterior partial vertebrectomy with 360-degree decompression in destructive thoracic spondylodiscitis.

BACKGROUND: Advanced states of vertebral osteomyelitis accompanied by spinal instability, epidural abscess formation, and neurological deficits require surgical decompression, stabilization, and often reconstruction of the anterior and posterior columns. The efficacy of a posterolateral approach with resection of inflammatory tissue, and interbody (titanium cages) and dorsal fusion was investigated and the clinical and radiological parameters (correction of kyphosis and fusion rates) were evaluated. METHOD: From 2011 to 2014, ten consecutive patients were treated at our institution using the modified technique of a transversecomy without costal resection to decompress neural structures and resect inflammatory tissue in destructive thoracic vertebral osteomyelitis. Flattening of the endplates without complete corpectomy, 360-degree stabilization, and correction of kyphosis by posterior shortening instead of anterior distraction were performed to avoid an additional ventral approach. Clinical and radiological data were retrospectively analyzed. RESULTS: All ten patients (six male and four female, mean age, 66 years) suffered from severe and destructive osteomyelitis. Surgery was performed successfully in all ten patients. Mean surgical time was 308 min. Mean follow-up was 19 months (range, 2-32 months). Neither approach-related or pulmonary complications nor recurrence of osteomyelitis were observed. All patients experienced pain relief after the procedure (mean back pain VAS was 8.8 pre-treatment and 3.2 at the final follow-up). Fusion was observed in all patients on the basis of computerized tomography scans. The mean radiological segmental kyphosis was corrected from 20° preoperatively to 7° after surgery and 9° at the final follow-up. CONCLUSIONS: The modified posterior transversectomy with 360-degree decompression and anterior wall reconstruction with titanium cages in combination with posterior instrumentation for sagittal alignment correction is a reliable, effective, and safe treatment option.

Influence of the transverse tarsal arch on radiological components of progressive collapsing foot deformity.

The importance of the transverse tarsal arch (TTA) has recently been extensively reevaluated and has even been considered to play a greater role in foot stability than the medial longitudinal arch (MLA). However, the relevance of this observation in the context of common clinical foot disorders, such as progressive collapsing foot deformity (PCFD), has not yet been fully clarified. In this biomechanical study, we examined ten pairs of human cadaveric feet by serial weight-bearing cone-beam computed tomography under controlled loading using a custom-designed testing machine. The MLA and TTA were transected separately, alternating the order in two study groups. A semiautomated three-dimensional evaluation of their influence on three components of PCFD, namely collapse of the longitudinal arch (sagittal Meary's angle), hindfoot alignment (sagittal talocalcaneal angle), and forefoot abduction (axial Meary's angle), was performed. Both arches had a relevant effect on collapse of the longitudinal arch, however the effect of transecting the MLA was stronger compared to the TTA (sagittal Meary's angle, 7.4° (95%CI 3.8° to 11.0°) vs. 3.2° (95%CI 0.5° to 5.9°); p = 0.021). Both arches had an equally pronounced effect on forefoot abduction (axial Meary's angle, 4.6° (95%CI 2.0° to 7.1°) vs. 3.0° (95%CI 0.6° to 5.3°); p = 0.239). Neither arch showed a consistent effect on hindfoot alignment. In conclusion, weakness of the TTA has a decisive influence on radiological components of PCFD, but not greater than that of the MLA. Our findings contribute to a deeper understanding and further development of treatment concepts for flatfoot disorders.

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.

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.