Camilo Molina, Daniel M. Sciubba, Christopher Chaput, P. Justin Tortolani, George I. Jallo and Ryan M. Kretzer
Translaminar screws (TLSs) were originally described as a safer alternative to pedicle and transarticular screw placement at C-2 in adult patients. More recently, TLSs have been used in both the cervical and thoracic spine of pediatric patients as a primary fixation technique and as a bailout procedure when dysplastic pedicle morphology prohibits safe pedicle screw placement. Although authors have reported the anatomical characteristics of the cervical and thoracic lamina in adults as well as those of the cervical lamina in pediatric patients, no such data exist to guide safe TLS placement in the thoracic spine of the pediatric population. The goal of this study was to report the anatomical feasibility of TLS placement in the thoracic spine of pediatric patients.
Fifty-two patients (26 males and 26 females), with an average age of 9.5 ± 4.8 years, were selected by retrospective review of a trauma registry database after institutional review board approval. Study inclusion criteria were an age from 2 to 16 years, standardized axial bone-window CT images of the thoracic spine, and the absence of spinal trauma. For each thoracic lamina the following anatomical features were measured using eFilm Lite software: laminar width (outer cortical and cancellous), laminar height (LH), maximal screw length, and optimal screw trajectory. Patients were stratified by age (an age < 8 versus ≥ 8 years) and sex.
Collected data demonstrate the following general trends as one descends the thoracic spine from T-1 to T-12: 1) increasing laminar width to T-4 followed by a steady decrease to T-12, 2) increasing LH, 3) decreasing maximal screw length, and 4) increasing ideal screw trajectory angle. When stratified by age and sex, male patients older than 8 years of age had significantly larger laminae in terms of both width and height and allowed significantly longer screw placement at all thoracic levels compared with their female counterparts. Importantly, it was found that 78% of individual thoracic laminae, regardless of age or sex, could accept a 4.0-mm screw with 1.0 mm of clearance. As expected, when stratifying by age and sex, it was found that older male patients had the highest acceptance rates.
Data in the present study provide information regarding optimal TLS length, diameter, and trajectory for each thoracic spinal level in pediatric patients. Importantly, the data collected demonstrate no anatomical limitations within the pediatric thoracic spine to TLS instrumentation, although acceptance rates are lower for younger (< 8 years old) and/or female patients. Lastly, given the anatomical variation found in this study, CT scanning can be useful in the preoperative setting when planning TLS use in the thoracic spine of pediatric patients.
Taylor E. Purvis, C. Rory Goodwin, Camilo A. Molina, Steven M. Frank and Daniel M. Sciubba
The aim of this study was to characterize the association between percentage change in hemoglobin (ΔHb)—i.e., the difference between preoperative Hb and in-hospital nadir Hb concentration—and perioperative adverse events among spine surgery patients.
Patients who underwent spine surgery at the authors’ institution between December 4, 2008, and June 26, 2015, were eligible for this retrospective study. Patients who underwent the following procedures were included: atlantoaxial fusion, subaxial anterior cervical fusion, subaxial posterior cervical fusion, anterior lumbar fusion, posterior lumbar fusion, lateral lumbar fusion, excision of intervertebral disc, and excision of spinal cord lesion. Data on intraoperative transfusion were obtained from an automated, prospectively collected, anesthesia data management system. Data on postoperative hospital transfusions were obtained through an Internet-based intelligence portal. Percentage ΔHb was defined as: ([preoperative Hb − nadir Hb]/preoperative Hb) × 100. Clinical outcomes included in-hospital morbidity and length of stay associated with percentage ΔHb.
A total of 3949 patients who underwent spine surgery were identified. Of these, 1204 patients (30.5%) received at least 1 unit of packed red blood cells. The median nadir Hb level was 10.6 g/dl (interquartile range 8.7–12.4 g/dl), yielding a mean percentage ΔHb of 23.6% (SD 15.4%). Perioperative complications occurred in 234 patients (5.9%) and were more common in patients with a larger percentage ΔHb (p = 0.017). Hospital-related infection, which occurred in 60 patients (1.5%), was also more common in patients with greater percentage ΔHb (p = 0.001).
Percentage ΔHb is independently associated with a higher risk of developing any perioperative complication and hospital-related infection. The authors’ results suggest that percentage ΔHb may be a useful measure for identifying patients at risk for adverse perioperative events.
Seba Ramhmdani, Marc Comair, Camilo A. Molina, Daniel M. Sciubba and Ali Bydon
Interspinous process devices (IPDs) have been developed as less-invasive alternatives to spinal fusion with the goal of decompressing the spinal canal and preserving segmental motion. IPD implantation is proposed to treat symptoms of lumbar spinal stenosis that improve during flexion. Recent indications of IPD include lumbar facet joint syndrome, which is seen in patients with mainly low-back pain. Long-term outcomes in this subset of patients are largely unknown. The authors present a previously unreported complication of coflex (IPD) placement: the development of a large compressive lumbar synovial cyst. A 64-year-old woman underwent IPD implantation (coflex) at L4–5 at an outside hospital for low-back pain that occasionally radiates to the right leg. Postoperatively, her back and right leg pain persisted and worsened. MRI was repeated and showed a new, large synovial cyst at the previously treated level, severely compressing the patient’s cauda equina. Four months later, she underwent removal of the interspinous process implant, bilateral laminectomy, facetectomy, synovial cyst resection, interbody fusion, and stabilization. At the 3-month follow-up, she reported significant back pain improvement with some residual leg pain. This case suggests that facet arthrosis may not be an appropriate indication for placement of coflex.
Camilo A. Molina, Rachel Sarabia-Estrada, Ziya L. Gokaslan, Timothy F. Witham, Ali Bydon, Jean-Paul Wolinsky and Daniel M. Sciubba
Recombinant human bone morphogenetic proteins (rhBMPs) are FDA-approved for specific spinal fusion procedures, but their use is contraindicated in spine tumor resection beds because of an unclear interaction between tumor tissue and such growth factors. Interestingly, a number of studies have suggested that BMPs may slow the growth of adenocarcinomas in vitro, and these lesions represent the majority of bony spine tumors. In this study, the authors hypothesized that rhBMP-2 placed in an intraosseous spine tumor in the rat could suppress tumor and delay the onset of paresis in such animals.
Twenty-six female nude athymic rats were randomized into an experimental group (Group 1) or a positive control group (Group 2). Group 1 (tumor + 15 μg rhBMP-2 sponge, 13 rats) underwent transperitoneal exposure and implantation of breast adenocarcinoma (CRL-1666) into the L-6 spine segment, followed by the implantation of a bovine collagen sponge impregnated with 15 μg of rhBMP-2. Group 2 (tumor + 0.9% NaCl sponge, 13 rats) underwent transperitoneal exposure and tumor implantation in the lumbar spine but no local treatment with rhBMP-2. An additional 8 animals were randomized into 2 negative control groups (Groups 3 and 4). Group 3 (15 μg rhBMP-2 sponge, 4 rats) and Group 4 (0.9% NaCl sponge, 4 rats) underwent transperitoneal exposure of the lumbar spine along with the implantation of rhBMP-2– and saline-impregnated bovine collagen sponges, respectively. Neither of the negative control groups was implanted with tumor. The Basso-Beattie-Bresnahan (BBB) scale was used to monitor daily motor function regression and the time to paresis (BBB score ≤ 7).
In comparison with the positive control animals (Group 2), the experimental animals (Group 1) had statistically significant longer mean (25.8 ± 12.2 vs 13 ± 1.4 days, p ≤ 0.001) and median (20 vs 13 days) times to paresis. In addition, the median survival time was significantly longer in the experimental animals (20 vs 13.5 days, p ≤ 0.0001). Histopathological analysis demonstrated bone growth and tumor inhibition in the experimental animals, whereas bone destruction and cord compression were observed in the positive control animals. Neither of the negative control groups (Groups 3 and 4) demonstrated any evidence of neurological deterioration, morbidity, or cord compromise on either gross or histological analysis.
This study shows that the local administration of rhBMP-2 (15 μg, 10 μl of 1.5-mg/ml solution) in a rat spine tumor model of breast cancer not only fails to stimulate local tumor growth, but also decreases local tumor growth and delays the onset of paresis in rats. This preclinical experiment is the first to show that the local placement of rhBMP-2 in a spine tumor bed may slow tumor progression and delay associated neurological decline.
A. Karim Ahmed, Zachary Pennington, Camilo A. Molina, Yuanxuan Xia, C. Rory Goodwin and Daniel M. Sciubba
Effective en bloc resection of primary spinal tumors necessitates careful consideration of adjacent anatomical structures in order to achieve negative margins and reduce surgical morbidity. This can be particularly challenging in the cervical spine, where vital neurovascular and connective tissues are present in the region. Early multidisciplinary surgical planning that includes clinicians and engineers can both optimize surgical planning and enable a more feasible resection with oncological margins. The aim of the current work was to demonstrate two cases that involved multidisciplinary surgical planning for en bloc resection of primary cervical spine tumors, successfully utilizing 3D-printed patient models and neoadjuvant therapies.
A novel animal model of human breast cancer metastasis to the spine: a pilot study using intracardiac injection and luciferase-expressing cells
Presented at the 2012 Spine Section Meeting
Patricia Zadnik, Rachel Sarabia-Estrada, Mari L. Groves, Camilo Molina, Christopher Jackson, Edward McCarthy, Ziya L. Gokaslan, Ali Bydon, Jean-Paul Wolinsky, Timothy F. Witham and Daniel M. Sciubba
Metastatic spine disease is prevalent in cancer victims; 10%–30% of the 1.2 million new patients diagnosed with cancer in the US exhibit spinal metastases. Unfortunately, treatments are limited for these patients, as disseminated disease is often refractory to chemotherapy and is difficult to treat with surgical intervention alone. New animal models that accurately recapitulate the human disease process are needed to study the behavior of metastases in real time.
In this study the authors report on a cell line that reliably generates bony metastases following intracardiac injection and can be tracked in real time using optical bioluminescence imaging. This line, RBC3, was derived from a metastatic breast adenocarcinoma lesion arising in the osseous spine of a rat following intracardiac injection of MDA-231 human breast cancer cells.
Upon culture and reinjection of RBC3, a statistically significantly increased systemic burden of metastatic tumor was noted. The resultant spine lesions were osteolytic, as demonstrated by small animal CT scanning.
This cell line generates spinal metastases that can be tracked in real time and may serve as a useful tool in the study of metastatic disease in the spine.
Camilo A. Molina, Christopher P. Ames, Dean Chou, Laurence D. Rhines, Patrick C. Hsieh, Patricia L. Zadnik, Jean-Paul Wolinsky, Ziya L. Gokaslan and Daniel M. Sciubba
Chordomas involving the mobile spine are ideally managed via en bloc resection with reconstruction to optimize local control and possibly offer cure. In the cervical spine, local anatomy poses unique challenges, limiting the feasibility of aggressive resection. The authors present a multi-institutional series of 16 cases of cervical chordomas removed en bloc. Particular attention was paid to clinical outcome, complications, and recurrence. In addition, outcomes were assessed according to position of tumor at the C1–2 level versus the subaxial (SA) spine (C3–7).
The authors reviewed cases involving patients who underwent en bloc resection of cervical chordoma at 4 large spine centers. Patients were included if the lesion epicenter involved the C-1 to C-7 vertebral bodies. Demographic data and details of surgery, follow-up course, exposure to adjuvant therapy, and complications were obtained. Outcome was correlated with presence of tumor in C1–2 versus subaxial spine via a Student t-test.
Sixteen patients were identified (mean age at presentation 55 ± 14 years). Seven cases (44%) cases involved C1–2, and 16 involved the subaxial spine. Median survival did not differ significantly different between the C1–2 (72 months) and SA (60 months) groups (p = 0.65). A combined (staged anteroposterior) approach was used in 81% of the cases. Use of the combined approach was significantly more common in treatment of subaxial than C1–2 tumors (100% vs 57%, p = 0.04). En bloc resection was attempted via an anterior approach in 6% of cases (C1–2: 14.3%; SA: 0%; p = 0.17) and a posterior approach in 13% of cases (C1–2: 29%; SA: 0%; p = 0.09). The most commonly reported margin classification was marginal (56% of cases), followed by violated (25%) and wide (19%). En bloc excision of subaxial tumors was significantly more likely to result in marginal margins than excision of C1–2 tumors (C1–2: 29%; SA: 78%; p = 0.03). C1–2 tumors were associated with significantly higher rates of postoperative complications (C1–2: 71%; SA: 22%; p = 0.03). Both local and distant tumor recurrence was greatest for C1–2 tumors (local C1–2: 29%; local SA: 11%; distant C1–2: 14%; distant SA: 0%). Statistical analysis of tumor recurrence based on tumor location was not possible due to the small number of cases. There was no between-groups difference in exposure to postoperative adjuvant radiotherapy. There was no difference in median survival between groups receiving proton beam radiotherapy or intensity-modulated radiotherapy versus no radiation therapy (p = 0.8).
Compared with en bloc resection of chordomas involving the subaxial cervical spine, en bloc resection of chordomas involving the upper cervical spine (C1–2) is associated with poorer outcomes, such as less favorable margins, higher rates of complications, and increased tumor recurrence. Data from this cohort do not support a statistically significant difference in survival for patients with C1–2 versus subaxial disease, but larger studies are needed to further study survival differences.
Patricia L. Zadnik, Camilo A. Molina, Rachel Sarabia-Estrada, Mari L. Groves, Michele Wabler, Jana Mihalic, Edward F. McCarthy, Ziya L. Gokaslan, Robert Ivkov and Daniel Sciubba
The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure.
A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee.
Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction.
Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.