Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into account. The aim of this study was to ascertain whether receptors are associated with survival, when the disease has progressed up to SBM. All patients who were treated for SBM from breast cancer between 2005 and 2012 were included in this international multi-center retrospective study (n = 111). Reports were reviewed for ER, PR and HER2 status and subsequently subdivided into one of four categories; luminal A, luminal B, HER2 and triple negative. Survival time was calculated as the difference between start of treatment for SBM and date of death. Analysis was performed using the Kaplan-Meier method and log-rank tests. Median follow-up was 3.7 years. Survival times in the luminal B and HER2 categories were not significantly different to the luminal A category and were joined into a single receptor positive category. Eighty-five patients (77 %) had a receptor positive phenotype and 25 (23 %) had a triple negative phenotype. Median survival time was 22.5 months (95 %CI 18.0-26.9) for the receptor positive category and 6.7 months (95 %CI 2.4-10.9) for the triple negative category (p < 0.001). Patients with SBM from breast cancer with a triple negative phenotype have a shorter survival time than patients with a receptor positive phenotype. Models estimating survival should be adjusted accordingly.

1997 Volvo Award winner in clinical studies. The effect of pedicle screw instrumentation on functional outcome and fusion rates in posterolateral lumbar spinal fusion: a prospective, randomized clinical study.

STUDY DESIGN: A prospective randomized clinical study. OBJECTIVES: To evaluate supplementary pedicle screw fixation (Cotrel-Dubousset) in posterolateral lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: The rationale behind lumbar fusion is to eliminate pathologic motion to relieve pain. To improve fusion rates and to allow reduction, a rigid transpedicular screw fixation may be beneficial, but the positive effect of this may be counter-balanced by an increase in complications. METHODS: The inclusion criteria were severe, chronic low back pain from spondylolisthesis Grades 1 and 2 or from primary or secondary degenerative segmental instability. One hundred thirty patients were randomly allocated to receive no instrumentation (n = 66) or Cotrel-Dubousset instrumentation (n = 64) in posterolateral lumbar fusion. Variables were registered at the time of surgery and at 1 and 2 years after surgery. RESULTS: Follow-up was achieved in 97.7% of the patients. Fusion rates deduced from plain radiographs were not significantly different between instrumented and noninstrumented groups. The functional outcome assessed by the Dallas Pain Questionnaire improved significantly in both groups, and there were no significant differences in results between the two groups, except for significantly better (P < 0.06) functional outcome in relation to daily activities in the instrumented group when neural decompression had been performed. The global patients' satisfaction was 82% in the instrumented group versus 74% in the noninstrumented group (not significant). Fixation of instrumentation increased operation time, blood loss, and early reoperation rate significantly. Patients experienced only a few minor postoperative complications; none were major. Two infections appeared in the Cotrel-Dubousset group. Significant symptoms from misplacement of pedicle screws were seen in 4.8% of the instrumented patients. CONCLUSIONS: Lumbar posterolateral fusion with pedicle screw fixation increases the operation time, blood loss, and reoperation rate, and leads to a significant risk of nerve injury. The functional outcome improves significantly with high patient satisfaction, with or without instrumentation. No significant differences were observed between the two groups in functional outcome and fusion rate. The only gain in functional outcome from instrumentation was found in the daily activity category in patients with supplementary neural decompression. The results of this study do not justify the general use of pedicle screw fixation alone as an adjunct to posterolateral lumbar fusion.

Interobserver and intraobserver agreement of radiograph interpretation with and without pedicle screw implants: the need for a detailed classification system in posterolateral spinal fusion.

STUDY DESIGN: A prospective randomized clinical study in which four observers evaluated radiographs of posterolateral fusion masses. OBJECTIVES: To evaluate the accuracy of radiograph interpretation of the posterolateral spinal fusion mass when using a detailed classification system and to analyze the influence of metallic internal fixation devices on radiologic inaccuracy. SUMMARY OF BACKGROUND DATA: In general, the literature describing the classification criteria used for radiograph interpretation of spinal posterolateral fusion has serious deficiencies. There is a need for a detailed classification system. METHODS: Seventy patients were randomly allocated to receive no instrumentation (n = 36) or Cotrel-Dubousset instrumentation (n = 34) in posterolateral lumbar fusion. All four observers participated in a prestudy discussion and evaluated the radiographs (anteroposterior, lateral) taken at the 1-year follow-up evaluation. The observers scored the radiographs twice (30 days apart). Each level on each side was judged separately. A continuous intertransverse bony bridge involving at minimum one of the two sides indicated a fusion at that level. "Fusion" indicated this quality of fusion at all intended levels. If the fusion was doubtful on both sides of the interspace, the individual case could not be classified as "fused." RESULTS: The mean interobserver agreement was 86% (Kappa 0.53), and the mean intraobserver agreement was 93% (Kappa 0.78). No difference in interobserver and intraobserver agreement was found between patients with and without supplementary pedicle screw fixation. All mean Kappa values were classified as fair or good. The four observers identified a mean fusion rate of 81%. CONCLUSION: It is extremely difficult to interpret radiographic lumbar posterolateral fusion success. Such an assessment needs to be performed by use of a detailed radiographic classification system. The classification system presented here revealed good interobserver and intraobserver agreement, both with and without instrumentation. The classification showed acceptable reliability and may be one way to improve interstudy and intrastudy correlation of radiologic outcomes after posterolateral spinal fusion. Instrumentation did not influence reproducibility but may result in slightly underestimated fusion rates.

[Intraoperative autologous transfusion (erythrocyte saving) in surgery for scoliosis. A case-controlled study]. / Intraoperativ autolog transfusion (erytrocytgenvinding) ved skoliosekirurgi. En case-kontrolunderslgelse.

A Haemonatics Cell Saver 3+ was used for intraoperative autologous transfusion in a case control study of 20 patients with idiopathic adolescent scoliosis. Ten of the patients were treated surgically by Cotrel-Dubousset instrumentation (CDI) with intraoperative autologous transfusion and ten patients were submitted to Harrington' method of operation with device for transverse traction (DTT). In the CDI group the mean peroperative blood loss was 1,700 ml and a mean of 804 ml or 69% was transfused intraoperatively with a hematocrit of 60%. Out of a total blood loss of 2,701 ml 44% of the red blood-cells were autotransfused in all. Seven patients did not required blood transfusion and two patients did not require blood transfusion postoperatively. In the Harrington group the mean total blood loss the was 2,390 ml and the mean peroperative blood loss was 1,715 ml. The total requirement for transfusion was 34 units peroperative and 15 units postoperatively. In a series of ten patients submitted to operative treatment for scoliosis, the need for blood transfusion was reduced by 49% compared with a control group.

[Spinal fractures in adults in bob-sled accidents]. / Columnafrakturer hos voksne efter styrt på plasticbobslaede.

A case study of two adults who sustained severe burst fractures of the thoracolumbar spine (T12, L1) after trivial accidents using plastic sledges. In one case a transient conus medullaris lesion was encountered. The fractures were reduced indirectly by internal fixation as well as by direct anteposition of the fragments from the spinal canal after laminectomy. The fracture mechanism is probably a result of hyperflexion combined with very little shock absorbtion from this sledgetype. Plastic sledges seem particularly hazardous for adults.

[Congenital kyphoscoliosis complicated by paraplegia]. / Kongenit kyfoskoliose kompliceret med paraplegi.

Congenital scoliosis accounts for 10% of all scolioses which require treatment. Correct treatment demands an exact and early detection of the deformity. Early intervention may only require a minor operation. Two cases are presented with paraplegia as the first presenting symptom of congenital kyphoscoliosis. In both cases anterior decompression and spondylodesis was followed by early neurological recovery. After a second operation with posterior spondylodesis and instrumentation ad modum Cotrel-Dubousset the patients were mobilised. Patients with congenital spinal deformity ought to be investigated and treated in a highly specialized department of spinal surgery.

[Results after surgical treatment of unstable thoracolumbar fractures]. / Resultat efter operativ behandling af ustabile torakolumbale columnafrakturer.

Seventy-eight patients with unstable, one-level fracture of the thoracolumbar spine and no neurological impairment were treated with short segment fixation, transpedicular autologous bone transplantation and posterolateral fusion. Kyphotic deformity and anterior column height improved significantly. Complications consisted of one case of late deep infection, three cases of seroma, four cases with 5 mm schantz screw breakage and two cases with screw loosening. Mild to moderate pain was present in 79% of the patients at follow-up, median 32 (13-72) months. Sixty-seven percent of the patients had returned to previous activity levels of employment. Short posterior internal fixation, transpedicular transplantation and posterolateral fusion allowed neurologically intact patients to be mobilized early, to spend median 12 days in hospital, and carried no risk of deterioration in neurological function.

[Stimulation of bone healing with growth factors in orthopedic surgery]. / Stimulation af knogleheling med vaekstfaktorer inden for ortopaedkirurgien.

Growth factors with specific effects on bone cells have been known of for more than a decade. Clinical usage of growth factors has recently become possible due to recombinant gene technology. In vivo studies over the last five years have demonstrated that growth factors can stimulate bone formation and bone healing and these results have made growth factors candidates for future clinical use in orthopaedic surgery. Growth factors for clinical use will become commercially available in the near future. The aim of this review paper is to describe the most important growth factors with effect on bone tissue and to give an updated review on experimental and clinical data on growth factor mediated bone healing in situations related to orthopaedic surgery. Possible areas for future clinical usage of growth factors are also discussed.

[Anterior lumbar intercorporal spondylodesis. Radiological and functional therapeutic results]. / Forreste lumbal interkorporal spondylodese. Radiologisk og funktionelt behandlingsresultat.

The purpose of this investigation was to identify risk factors in relation to non-union following lumbar intercorporal spondylodesis and to correlate this result with the functional outcome as assessed by the Dallas Pain Questionnaire (DPQ). This comprises questions concerning daily activities, work-leisure activities, anxiety-depression and social interest, measured on visual analog scales. During the period 1979-87 a total of 132 patients were operated with spondylodesis, diagnosed as suffering from spondylolisthesis or disc degeneration. Minimal follow-up was one year. Radiological graft incorporation was complete in 52% of the cases, partial in 24% and lacking in 24%. The rate of functional outcome follow-up was 72%. Seventy percent claimed an improvement in three out of four categories. Thirty percent claimed no improvement or worsened condition. The DPQ showed signs of poor prognosis for age groups above 45 (p < 0.04) and those with former spine surgery (p < 0.02). The questionnaire showed significantly better results for the group with perfect or doubtful union compared to the group with non-union (p < 0.006). In conclusion this investigation demonstrates a success rate of 70% for anterior lumbar interbody fusion. There is a tendency to poorer prognosis for patients with previous spine surgery and age above 45 years. The Dallas Pain Questionnaire correlates significantly to X-ray analysis and seems to be a useful tool for the description of individual biopsychosocial changes following spine surgery.

[The effect of pedicle screw instrumentation on posterolateral spinal fusion. A prospective, randomized study with a two-year follow-up]. / Effekten af pedikelskrueinstrumentering ved posterolateral lumbal spondylodese. Et prospektivt randomiseret studium med to års opfølgning.

The aim was to evaluate the effect of supplementary pedicle screw fixation (Cotrel-Dubousset [CD]) in posterolateral lumbar spinal fusion. The study comprises 130 patients undergoing lumbar or lumbosacral fusion for spondyloisthesis grades I-II or degenerative segmental instability conditions. The patients were randomly allocated for no instrumentation (n = 66) or CD instrumentation (n = 64) in posterolateral lumbar fusion. A 97.7% follow-up was achieved. There were no significant differences between the two groups concerning fusion rates assessed by X-ray or functional outcomes assessed by Dallas Pain Questionnaire. The global patient satisfaction was 82% in the instrumented group versus 74% in the noninstrumented group. Instrumentation increased both operation time, blood loss, and early re-operation rates significantly. A high patient satisfaction was found in both groups. However, the results from this study do not justify the general use of pedicle screw fixation alone as an adjunct to posterolateral lumbar fusion.

Control of proliferation and osteogenic differentiation of human dental-pulp-derived stem cells by distinct surface structures.

The ability to control the behavior of stem cells provides crucial benefits, for example, in tissue engineering and toxicity/drug screening, which utilize the stem cell's capacity to engineer new tissues for regenerative purposes and the testing of new drugs in vitro. Recently, surface topography has been shown to influence stem cell differentiation; however, general trends are often difficult to establish due to differences in length scales, surface chemistries and detailed surface topographies. Here we apply a highly versatile screening approach to analyze the interplay of surface topographical parameters on cell attachment, morphology, proliferation and osteogenic differentiation of human mesenchymal dental-pulp-derived stem cells (DPSCs) cultured with and without osteogenic differentiation factors in the medium (ODM). Increasing the inter-pillar gap size from 1 to 6 µm for surfaces with small pillar sizes of 1 and 2 µm resulted in decreased proliferation and in more elongated cells with long pseudopodial protrusions. The same alterations of pillar topography, up to an inter-pillar gap size of 4 µm, also resulted in enhanced mineralization of DPSCs cultured without ODM, while no significant trend was observed for DPSCs cultured with ODM. Generally, cells cultured without ODM had a larger deposition of osteogenic markers on structured surfaces relative to the unstructured surfaces than what was found when culturing with ODM. We conclude that the topographical design of biomaterials can be optimized for the regulation of DPSC differentiation and speculate that the inclusion of ODM alters the ability of the cells to sense surface topographical cues. These results are essential in order to transfer the use of this highly proliferative, easily accessible stem cell into the clinic for use in cell therapy and regenerative medicine.

Retrograde ejaculation after retroperitoneal lower lumbar interbody fusion.

We have studied the incidence and functional outcome of retrograde ejaculation as a postoperative complication of anterior lumbar interbody fusion. A questionnaire, specifically designed to analyse this problem, has been used over a 6 to 13 year follow-up. Out of 50 men, 41 completed the questionnaire; 2 complained they had permanent retrograde ejaculation after the operation; one stopped ejaculating for 6 months, and thereafter had a 50% reduction. The Dallas pain questionnaire showed that retrograde ejaculation did not have a negative effect on the functional outcome, but male genital dysfunction was a complication of anterior spinal fusion in 8% of cases.

Radiological and functional outcome after anterior lumbar interbody spinal fusion.

Outcome after anterior spinal fusion has mainly been studied radiologically and reported fusion rates vary greatly. The aim of this study was to investigate radiological and long-term clinical outcome. The study comprised 120 consecutive patients, operated on during the period 1979-1987, with single-or two-level anterior interbody spinal fusion due to disc degeneration or isthmic spondylolisthesis with lumbar instability. In 64 patients a supplemental facet joint fusion was performed. Clinical outcome was evaluated 5-13 years after surgery using the patient-administered Dallas Pain Questionnaire (DPQ). Radiological outcome was determined on the basis of radiographs taken at a 2-year follow-up assessed by independent observers. The radiological follow-up rate was 98%. Complete fusion was found in 52%, questionable fusion in 24%, and definitive pseudoarthrosis in 24% of patients. Radiological results were poor in patients who had undergone previous spinal surgery (P < 0.05) and in those with two-level fusion (P < 0.05). The DPQ reply rate was 80%. Sixty-six patients claimed improvement in all functional groups. Patients with complete or questionable union had significantly better results than did those with non-union (P < 0.01). Poorer functional outcome was found in patients who had undergone previous spinal surgery (P < 0.01) or fusion at the L4/L5 level (P < 0.05), in those who had responded poorly to the preoperative test brace (P < 0.05), and in those above 45 years old at the time of surgery (P < 0.05). Radiological and functional outcome did not vary according to whether patients were treated postoperatively with a plaster jacket or with facet screw fixation. The study demonstrated a functional success rate of approximately 66% following anterior lumbar spinal fusion after a mean follow-up of 8 years. There was a clear tendency for poorer prognosis for patients who had undergone previous spinal surgery, those aged above 45 years, those operated at the L4/L5 level and those who had responded poorly to the preoperative test brace. DPQ scores correlated well with radiological outcome.

Functional outcome after posterolateral spinal fusion using pedicle screws: comparison between primary and salvage procedure.

Lumbar spinal fusion is a commonly performed surgical procedure, yet both the indications for its performance and its results remain controversial. It is generally believed that apart from situations where obvious measurable instability exists, a repeat surgical procedure such as spinal fusion does not improve the functional outcome in more than an average of 50% of cases. The aim of this study was to analyse functional outcome after posterolateral lumbar or lumbosacral spinal fusion, comparing primary and salvage procedures. It was designed as a prospective case/referent study with a 2-year follow-up. A total of 39 patients underwent a short posterior fusion with Cotrel-Dubousset (CD) pedicle screw fixation after earlier surgery of the lumbar spine. Two patients were erroneously omitted from the study at the index, so 37 patients were included in the salvage group. In the same period, 69 patients underwent lumbar fusion with pedicle screw fixation (CD) as primary surgery (referent group). Functional outcome was assessed by means of the Dallas Pain Questionnaire preoperatively and 1 and 2 years postoperatively. Fusion rates were determined by ordinary X-ray evaluation by two independent observers. Patients who had undergone previous spinal surgery had a significant improvement in functional outcome in terms of daily activity, work and leisure-time activities and anxiety/depression. With regard to social functioning, a significantly inferior outcome was found after the salvage procedure. The return-to-work rates at 2 years after surgery were 50% in the salvage group and 53% in the referent group. There was a significant correlation between radiological evaluation of the fusion mass and the functional outcome. The fusion rate was 76% in the salvage group and 72% in the referent group. This study demonstrates that a posterolateral spinal fusion can be effectively used as a salvage procedure. The functional and radiological outcome of the patients with revision surgery did not differ from those of the group of patients who underwent primary surgery. There was, however a clear indication of inferior social functioning after revision surgery.

Functional outcome after partial reduction and 360 degree fusion in grade III-V spondylolisthesis in adolescent and adult patients.

Reduction of high-grade spondylolisthesis is a surgically demanding procedure, which has been reported to incur a relatively high risk of neurologic damage, pseudoarthrosis, and other complications. The aim of this study was to evaluate the radiographic and functional outcome in spondylolisthesis grade III-V, surgically treated with posterior decompression, L4- or L5-S1 CD instrumentation, partial reduction, and posterolateral fusion followed by anterior interbody fusion L5-S1 ad modum Kellogg-Speed. Thirteen patients, mean age 23.8 (range, 11-33) years were followed for mean 28.5 (range, 19-52) months. The anterior slip, lumbosacral angle, sagittal rotation angle and L4/SI angle were significantly improved from preoperatively to follow-up. No patients had neurologic, vascular, thromboembolic, or lung complications. Twelve patients reported a better or unchanged (3 patients) physical and emotional status. At follow-up, 10 patients were in full-time jobs or back to school. The method was safe and provided a stable rigid fixation with partial reduction of the deformity and a satisfactory functional outcome.

Posterolateral spinal fusion at unintended levels due to bone-graft migration: no effect on clinical outcome in 19/130 patients.

In a prospective randomized study, we evaluated the risk of lumbar posterolateral spinal fusion at an unintended level due to bone graft migration. 130 patients underwent fusion supplemented by pedicle screw fixation (Cotrell-Dubousset, 64 patients) or uninstrumented fusion (66 patients). This was assessed by two independent observers on antero-posterior, and lateral radiographs taken 1 year after surgery. All patients had ben operated on at the preoperatively planned levels. Both observers agreed that fusion had taken place at an unintended level in 19 cases (14%). We found a tendency towards a higher risk of this "complication" when using supplementary pedicle screw fixation. The functional outcome, assessed by the Dallas Pain Questionnaire and the Low Back Pain Rating scale, was similar in patients having fusion at an unintended level and in patients fused only at the intended levels. There was no difference between the two groups concerning reoperation rates, postoperative smoking or social status. We conclude that unintended fusion occurs and tends to be commoner with the use of pedicle screw instrumentation. However, this complication seems not to affect the functional outcome if fusion has taken place at the intended level.

Semiquantitative mRNA measurements of osteoinductive growth factors in human iliac-crest bone: expression of LMP splice variants in human bone.

Although osteotropic growth factors are known to play an important role in bone metabolism, knowledge about their expression in relation to age, sex and smoking remains limited. In this study we report mRNA levels of the recently discovered Lim mineralization protein splice variants (LMP-1, LMP-2, LMP-3) and the established osteotropic growth factors BMP-2, BMP-6, BMP-7, TGF-beta, IGF-I, IGF-II and b-FGF in human iliac crest bone. Standardized bone biopsy specimens were obtained from the iliac crest during graft harvesting in 62 patients (38 males, 24 females, mean age 44.7 years, range 13-78 years) undergoing spinal surgery. Samples were immediately stored in liquid nitrogen for PCR analysis. Semi-quantitative RT-PCR was performed for TGF-beta, IGF-I, IGF-II, BMP2, BMP-6, BMP7, bFGF, LMP-1, LMP-2 and LMP-3 using beta-actin as internal standard. Triplicate measurements were made of each growth factor and beta-actin. mRNA for all examined growth factors was detected in 69% of the specimens. The lowest degree of detection was present for b-FGF and BMP-2, both of which were found in 85% of the specimens. LMP-1 was detected in 98% of the specimens. LMP-2 in 94% and LMP-3 in 27%, respectively. LMP-1 was generally expressed in higher amounts than LMP-2 and LMP-3. Nondetectable levels of the growth factors were more frequent in the >60-year-old males compared with >60-year-old females ( P < 0.05) and <60-year-old males ( P < 0.01). LMP-1 expression was more variable among young individuals, but mean values were similar between age groups. TGF-beta, BMP-2 and BMP-7 values did not differ between age groups, but generally a higher variation was found among older patients. IGF-I values were significantly higher ( P < 0.05) in males over 60 years, whereas the highest level of bFGF mRNA was present in males younger than 20 years ( P < 0.05). In addition, regression analysis revealed correlation between BMP-2 and BMP-7 (R2 = 0.74, P < 0.0005), LMP-2 and BMP-2 (R2 = 0.27, P < 0.0005) and LMP-2 and bFGF (R2 = 0.40, P < 0.0005). In conclusion, we have demonstrated expression of LMP-1 and LMP-2 in human bone. LMP-1 was expressed in higher amounts and showed a higher degree of variation among young individuals. LMP-2 was correlated to a number of other growth factors, suggesting that LMPs may also play a role in human bone metabolism. Higher variation in the expression of TGF-beta, BMP-2 and BMP-7 was found in the older age groups, but whether or not this can be correlated to age-related changes in bone turnover requires further studies.