Faculty Bibliography

Metastases cause 90% of human cancer deaths. The metastatic cascade involves local invasion, intravasation, extravasation, metastatic site colonization, and proliferation. Although individual mediators of these processes have been investigated, interactions between these mediators remain less well defined. We previously identified a complex between receptor tyrosine kinase c-Met and β1 integrin in metastases. Using cell culture and in vivo assays, we found that c-Met/β1 complex induction promoted intravasation and vessel wall adhesion in triple-negative breast cancer cells, but did not increase extravasation. These effects may have been driven by the ability of the c-Met/β1 complex to increase mesenchymal and stem cell characteristics. Multiplex transcriptomic analysis revealed upregulated Wnt and hedgehog pathways after c-Met/β1 complex induction. A β1 integrin point mutation that prevented binding to c-Met reduced intravasation. OS2966, a therapeutic antibody disrupting c-Met/β1 binding, decreased breast cancer cell invasion and mesenchymal gene expression. Bone-seeking breast cancer cells exhibited higher levels of c-Met/β1 complex than parental controls and preferentially adhered to tissue-specific matrix. Patient bone metastases demonstrated higher c-Met/β1 complex than brain metastases. Thus, the c-Met/β1 complex drove intravasation of triple-negative breast cancer cells and preferential affinity for bone-specific matrix. Pharmacological targeting of the complex may have prevented metastases, particularly osseous metastases.

OBJECTIVE:Long-segment fusion in adult spinal deformity (ASD) is often needed, but more focal surgeries may provide significant relief with less morbidity. The minimally invasive spinal deformity surgery (MISDEF2) algorithm guides minimally invasive ASD surgery, but it may be useful in open ASD surgery. We classified ASD patients undergoing focal decompression, limited decompression and fusion, and full correction according to MISDEF2 and correlated outcomes. METHODS:A retrospective study of ASD patients treated by 2 surgeons at our hospital was performed. Inclusion criteria were: age > 50, minimum 2-year follow-up, and open ASD surgery. Tumor, trauma, and infections were excluded. Patients had open surgery including focal decompression, short segment fusion, or full scoliosis correction. All patients were categorized by MISDEF2 into 4 classes based upon spinopelvic parameters. Perioperative metrics were assessed. Radiographic correction, complications and reoperation were recorded. RESULTS:A total of 136 patients met inclusion criteria. Mean follow-up was 46 ± 15.8 months (range, 24-118 months). Forty-seven underwent full deformity correction, 71 underwent short segment fusion, and 18 underwent decompression alone. There were 24 cases of class I, 66 cases of class II, 23 cases of class III, and 23 cases of class IV patients. Patients in class I and II had perioperative complication rates of 0% and 16.7% and revision rates of 8% and 21.2% when undergoing focal decompression or limited fusion. However, class II patients undergoing full correction had higher perioperative complications rate (p = 0.03) and revision surgery rates (p = 0.047). This difference was not seen in class III patients (p > 0.05). All class IV patients underwent full correction, but they had higher perioperative complication rates (p < 0.019), comparable revision surgery rates (p = 0.27), and better radiographic realignment (p < 0.001). In addition, full deformity correction was associated with longer length of stay, increased blood loss, and longer operative time (p < 0.001). CONCLUSION/CONCLUSIONS:The MISDEF2 algorithm may help guide ASD surgical decision making even in open surgery, with focal treatment used in class I and II patients as a viable alternative and full correction implemented in class IV patients because of severe malalignment. However, class II patients with ASD undergoing full deformity correction do have higher complication rates.

OBJECTIVE:Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized complications of long-segment spinal fusion. Previous studies have suggested that ligament augmentation can decrease rates of PJF by reducing junctional stress and strengthening upper instrumented vertebrae (UIVs) and adjacent segments. However, there is a paucity of long-term data on the efficacy of ligament augmentation in preventing PJF. In this study, the authors sought to determine the effect of ligament augmentation on rates of PJF in a cohort of adult spinal deformity patients with at least 1 year of follow-up. METHODS:They conducted a retrospective analysis of ligament augmentation in a consecutive series of surgical patients with adult spinal deformity. Data on patient demographics, surgical characteristics, and surgery for PJF were collected. The minimum follow-up was 12 months. Univariate and multivariate analyses were performed to identify factors associated with reoperation for PJF. RESULTS:The authors identified a total of 242 patients (166 women [68.6%]) with ligament augmentation whose mean age was 66 years. The mean number of fused levels was 10, with a UIV distribution as follows: 90 upper thoracic UIVs (37.2%) and 152 lower thoracic UIVs (62.8%). Compared to a historical cohort of 77 patients treated before implementation of ligament augmentation, reoperation for PJF was significantly lower with ligament augmentation (15.6% vs 3.3%, p < 0.001). In a multivariate model, only ligament augmentation (OR 0.184, 95% CI 0.071-0.478, p = 0.001) and number of fused levels (OR 0.762, 95% CI 0.620-0.937, p = 0.010) were associated with reductions in reoperation for PJF. CONCLUSIONS:Ligament augmentation was associated with significant reductions in the rate of reoperation for PJF at 12 months in a cohort of adult spinal deformity patients. The most dramatic reduction was seen among patients with lower thoracic UIV. These data suggest that in appropriately selected patients, ligament augmentation may be a valuable adjunct for PJF reduction; however, long-term follow-up is needed.

The treatment of adult cervical deformity continues to be complex with high complication rates. However there are many new advancements and overall patients do well following surgical correction. To date there are now many types of cervical deformity that have been classified and there exists a variety of surgical options. These recent advances have been developed in the last few years and the field continues to grow at a rapid rate. Thus, the goal of this article is to provide an updated review of cervical sagittal balance including; cervical alignment parameters, deformity classification, clinical evaluation, with both conservative and surgical treatment options.

BACKGROUND:Operative treatment of adult spinal deformity (ASD) can be very challenging with high complication rates. It is well established that patients benefit from such treatment; however, the surgical outcomes for patients with severe sagittal deformity have not been reported. OBJECTIVE:To report the outcomes of patients undergoing surgical correction for severe sagittal deformity. METHODS:Retrospective review of a prospective, multicenter ASD database. Inclusion criteria: operative patients age ≥18, sagittal vertical axis (SVA) ≥15 cm, mismatch between pelvic incidence and lumbar lordosis (PI-LL) ≥30°, and/or lumbar kyphosis ≥5° with minimum 2 yr follow-up. Health-related quality of life (HRQOL) scores including minimal clinically important difference (MCID)/substantial clinical benefit (SCB), sagittal and coronal radiographic values, demographic, frailty, surgical, and complication data were collected. Comparisons between 2 yr postoperative and baseline HRQOL/radiographic data were made. P < .05 was significant. RESULTS:A total of 138 patients were included from 502 operative patients (54.3% Female, Average (Avg) age 63.3 ± 11.5 yr). Avg operating room (OR) time 386.2 ± 136.5 min, estimated blood loss (EBL) 1829.8 ± 1474.6 cc. A total of 71(51.4%) had prior fusion. A total of 89.9% were posterior fusion only. Mean posterior levels fused 11.5 ± 4.1. A total of 44.9% had a 3-column osteotomy. All 2 yr postoperative radiographic parameters were significantly improved compared to baseline (P < .001 for all). All 2yr HRQOL measures were significantly improved compared to baseline (P < .004 for all). A total of 46.6% to 73.8% of patients met either MCID/SCB for all HRQOL. A total of 74.6% of patients had at least 1 complication, 11.6% had 4 or more complications, 33.3% had minimum 1 major complication, and 42(30.4%) had a postop revision. CONCLUSION/CONCLUSIONS:Patients with severe sagittal malalignment benefit from surgical correction at 2 yr postoperative both radiographically and clinically despite having a high complication rate.

BACKGROUND:Rigid and ankylosed thoracolumbar spinal deformities require three-column osteotomy (3CO) to achieve adequate correction. For severe and multiregional deformities, multilevel 3CO is required but its use and outcomes are rarely reported. OBJECTIVE:To describe the use of multilevel pedicle subtraction osteotomy (PSO) in adult spinal deformity (ASD) patients with severe, rigid, and ankylosed multiregional deformity. METHODS:Retrospective review of 5 ASD patients who underwent multilevel PSO for the correction of severe fixed deformity and review the literature regarding the use of multilevel PSO. RESULTS:Five patients presented with spinal imbalance secondary to regional and multiregional spinal deformities involving the thoracolumbar spine. All patients underwent a single-stage two-level noncontiguous PSO, and 2 of the patients underwent a staged third PSO to treat deformity involving a separate spinal region. Significant radiographic correction was achieved with normalization of spinal alignment and parameters. Two-level PSO was able to provide greater than 80 degrees of sagittal plane correction in both the lumbar and thoracic spine. Two patients experienced new postoperative weakness which recovered to preoperative baseline at 3 to 6 mo follow-up. At most recent follow-up, 4 of the 5 patients gained significant pain relief and had improved functionality. CONCLUSION/CONCLUSIONS:Noncontiguous multilevel PSO is a formidable surgical technique. Additional risk (compared to single-level 3CO) comes in the form of greater blood loss and higher risk for postoperative weakness. Nonetheless, multilevel PSO is feasible and effective for correcting severe multiplanar and multiregional ASD, and patients gain significant benefits in increased functionality and pain relief.

Adult cervical deformity (ACD) has been shown to have a substantial impact on quality of life and overall health, with moderate to severe deformities resulting in significant disability and dysfunction. Fortunately, surgical management and correction of cervical sagittal imbalance can offer significant benefits and improvement in pain and disability. ACD is a heterogenous disease and specific surgical correction strategies should reflect deformity type (driver of deformity) and patient-related factors. Spinal rigidity is one of the most important considerations as soft tissue releases and osteotomies play a crucial role in cervical deformity correction. For ankylosed, fixed, and severe deformity, 3-column osteotomy (3CO) is often warranted. A 3CO can be done through combined anteriorposterior (vertebral body resection) and posterior-only approaches (open or closed wedge pedicle subtraction osteotomies [PSOs]). This article reviews the literature for currently published studies that report results on the use of 3CO for ACD, with a special concentration on posterior based 3CO (open and closed wedge PSO). More specifically, this review discusses the indications, radiographic corrective ability, and associated complications.

OBJECTIVE:Rigid multiplanar thoracolumbar adult spinal deformity (ASD) cases are challenging and many require a 3-column osteotomy (3CO), specifically asymmetrical pedicle subtraction osteotomy (APSO). The outcomes and additional risks of performing APSO for the correction of concurrent sagittal-coronal deformity have yet to be adequately studied. METHODS:The authors performed a retrospective review of all ASD patients who underwent 3CO during the period from 2006 to 2019. All cases involved either isolated sagittal deformity (patients underwent standard PSO) or concurrent sagittal-coronal deformity (coronal vertical axis [CVA] ≥ 4.0 cm; patients underwent APSO). Perioperative and 2-year follow-up outcomes were compared between patients with isolated sagittal imbalance who underwent PSO and those with concurrent sagittal-coronal imbalance who underwent APSO. RESULTS:A total of 390 patients were included: 338 who underwent PSO and 52 who underwent APSO. The mean patient age was 64.6 years, and 65.1% of patients were female. APSO patients required significantly more fusions with upper instrumented vertebrae (UIV) in the upper thoracic spine (63.5% vs 43.3%, p = 0.007). Radiographically, APSO patients had greater deformity with more severe preoperative sagittal and coronal imbalance: sagittal vertical axis (SVA) 13.0 versus 10.7 cm (p = 0.042) and CVA 6.1 versus 1.2 cm (p < 0.001). In APSO cases, significant correction and normalization were achieved (SVA 13.0-3.1 cm, CVA 6.1-2.0 cm, lumbar lordosis [LL] 26.3°-49.4°, pelvic tilt [PT] 38.0°-20.4°, and scoliosis 25.0°-10.4°, p < 0.001). The overall perioperative complication rate was 34.9%. There were no significant differences between PSO and APSO patients in rates of complications (overall 33.7% vs 42.3%, p = 0.227; neurological 5.9% vs 3.9%, p = 0.547; medical 20.7% vs 25.0%, p = 0.482; and surgical 6.5% vs 11.5%, p = 0.191, respectively). However, the APSO group required significantly longer stays in the ICU (3.1 vs 2.3 days, p = 0.047) and hospital (10.8 vs 8.3 days, p = 0.002). At the 2-year follow-up, there were no significant differences in mechanical complications, including proximal junctional kyphosis (p = 0.352), pseudarthrosis (p = 0.980), rod fracture (p = 0.852), and reoperation (p = 0.600). CONCLUSIONS:ASD patients with significant coronal imbalance often have severe concurrent sagittal deformity. APSO is a powerful and effective technique to achieve multiplanar correction without higher risk of morbidity and complications compared with PSO for sagittal imbalance. However, APSO is associated with slightly longer ICU and hospital stays.

BACKGROUND:Novel methods in predicting survival in patients with spinal metastases may help guide clinical decision-making and stratify treatments regarding surgery vs palliative care. OBJECTIVE:To evaluate whether the frailty/sarcopenia paradigm is predictive of survival and morbidity in patients undergoing surgery for spinal metastasis. METHODS:A total of 271 patients from 4 tertiary care centers who had undergone surgery for spinal metastasis were identified. Frailty/sarcopenia was defined by psoas muscle size. Survival hazard ratios were calculated using multivariate analysis, with variables from demographic, functional, oncological, and surgical factors. Secondary outcomes included improvement of neurological function and postoperative morbidity. RESULTS:Patients in the smallest psoas tertile had shorter overall survival compared to the middle and largest tertile. Psoas size (PS) predicted overall mortality more strongly than Tokuhashi score, Tomita score, and Karnofsky Performance Status (KPS). PS predicted 90-d mortality more strongly than Tokuhashi score, Tomita score, and KPS. Patients with a larger PS were more likely to have an improvement in deficit compared to the middle tertile. PS was not predictive of 30-d morbidity. CONCLUSION/CONCLUSIONS:In patients undergoing surgery for spine metastases, PS as a surrogate for frailty/sarcopenia predicts 90-d and overall mortality, independent of demographic, functional, oncological, and surgical characteristics. The frailty/sarcopenia paradigm is a stronger predictor of survival at these time points than other standards. PS can be used in clinical decision-making to select which patients with metastatic spine tumors are appropriate surgical candidates.

STUDY DESIGN/UNASSIGNED:Retrospective cohort study. OBJECTIVE/UNASSIGNED:Thoracolumbar 3-column osteotomy (3CO) is a powerful technique for correction of rigid adult spinal deformity (ASD). However, it can be associated with high-volume blood loss. This study seeks to investigate the efficacy and safety of tranexamic acid (TXA) in 3CO ASD patients. METHODS/UNASSIGNED:ASD patients who underwent 3CO from 2006 to 2019 were retrospectively reviewed. Outcomes were compared between TXA and non-TXA patients, and TXA doses. RESULTS/UNASSIGNED:= .190) stays. There were no differences in outcomes between TXA dosing subgroups. CONCLUSIONS/UNASSIGNED:Systemic TXA use during 3CO for ASD surgery was not associated with decreased blood loss. TXA patients had shorter operative times, but this was driven mainly by surgeon experience on multivariate analysis. Routine use of TXA is safe and does not increase the incidence of hypercoagulable complications even at high doses.