Characterization of Lumbar Lordosis: Influence of Age, Sex, Vertebral Body Wedging, and L4-S1.

STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: The objectives of the study were to determine the contributions to lumbar lordosis (LL) through both the vertebrae and the intervertebral disc (IVD), and to investigate the relationships between lumbar sagittal spine measurements and age and gender. SUMMARY OF BACKGROUND DATA: A small body of literature exists on the relative contributions of vertebral body and IVD morphology to LL, the effects of L4-S1 on overall LL, and the relationships/correlations between lumbar sagittal spine measurements. METHODS: Patients who met the inclusion criteria were retrospectively evaluated. Measurements included LL, pelvic incidence (PI), and % contributions of vertebral body wedging/IVD wedging/L4-S1 to LL. Patients were separated into groups by age and sex, demographic data were collected, and statistical analysis was completed. RESULTS: LL decreased with age, although PI remained similar. Females demonstrated increased LL and vertebral body wedging % than males. Males demonstrated increased L4-S1% than females. Despite a decrease in LL with age, patients maintained L4-S1% and IVD wedging %. There was a significant negative relationship between PI and IVD wedging, PI and L4-S1%, and LL and L4-S1%. CONCLUSIONS: During aging, the lumbar spine loses LL linearly. This occurs in the IVD and vertebral bodies. Females have increased LL compared with males, because of an increase in vertebral body wedging and IVD/vertebral wedging cranial to L4. In patients with high PI or LL, increased LL occurs from cranial to L4 and from vertebral body wedging.

Triangular Osteosynthesis as a Treatment of Lumbopelvic Dissociation with Acute Cauda Equina Syndrome in an 11-Year-Old Patient.

This case offers a safe and effective method for treating lumbopelvic dissociation in a pediatric patient with cauda equina syndrome using a triangular osteosynthesis construct. After a high-speed accident, an 11-year-old girl was admitted to the hospital with bowel and bladder incontinence and bilateral lower extremity weakness. The orthopaedic trauma and spine teams elected for surgical treatment with a triangular osteosynthesis construct, a procedure usually reserved for adults. The surgery was uncomplicated, and the patient experienced complete resolution of her preoperative symptoms. She is doing well over 1-year postoperatively, with full neurologic recovery, maintained reduction, bony healing, and subsequent implant removal. To our knowledge, this is the youngest reported case of lumbopelvic dissociation treated in this manner and represents a viable treatment option.

Applications of Carbon Fiber Instrumentation in Spinal Oncology: Recent Innovations in Spinal Instrumentation and 2-Dimensional Illustrative Operative Video.

BACKGROUND: The management of spinal oncology necessitates a multimodal approach, with surgical intervention, radiation-based therapy, and postoperative advanced imaging. These systems must work well together to provide optimal patient outcomes. Traditional metallic spinal implants produce image artifacts and lead to radiation dose attenuation, which inhibit both disease monitoring and disease treatment, respectively. OBJECTIVE: To demonstrate the feasibility of an improved biomaterial implant that provides structural stability, while also allowing for disease monitoring and treatment in spinal oncology patients. METHODS: From February 2021 to September 2021, 3 patients with spinal oncologic deformity requiring resection and posterior spinal stabilization underwent fixation with polyether ether ketone-carbon fiber implants at a single academic institution. RESULTS: Patient ages ranged from 23 to 74 years (mean: 44.7 years). All patients underwent posterior spinal fixation using standard approaches. They each received polyether ether ketone-carbon fiber pedicle screw and rod implants, placed in standard fashion. There were no dural tears, postoperative wound infections, or other complications related to their treatment. Postoperative surveillance revealed gross total resection of the targeted tumor on postoperative radiographic imaging. CONCLUSION: Polyether ether ketone-carbon fiber implants are a safe and effective option for the treatment of thoracolumbar posterior spinal pathology. The utilization of this novel type of instrumentation in posterior spinal approaches may provide benefit to patients with spinal tumors over existing forms of posterior spinal instrumentation.

Distal Ventral Iliac Pathway for Spinopelvic Fixation: Technique Description and Case Series.

BACKGROUND: Pelvic fixation improves the stability of spinal instrumentation and can be used in high-grade degenerative disease, trauma, deformity, and destabilizing invasive pathologies, such as infection and tumor. Classic techniques for spinopelvic fixation include traditional iliac screws and S2-Alar-Iliac screws. We present a case series describing the distal ventral iliac pathway (DVIP) for spinopelvic fixation and discuss surgical indications and merits of this technique. We describe the use of the DVIP for spinopelvic fixation in the setting of degenerative and traumatic pathologies, compare this technique with existing approaches, and summarize literature to support this approach. METHODS: One hundred twenty-eight cases of DVIP screws were identified at 1 academic medical center, and 3 cases were chosen as representative examples for technique demonstration. RESULTS: Patient ages ranged from 19 to 81 (mean 62) years. Intraoperative and postoperative complications include 12 incidental durotomies, 3 suprafascial infections, and 2 compressive hematomas. There were 22 instances of hardware failure and 8 instances of pseudoarthrosis. Overall, 26 patients underwent revision surgery. Mean estimated blood loss, operative time, and time under fluoroscopy were 1959 mL, 386 minutes, and 3.19 minutes, respectively. CONCLUSIONS: The DVIP is both safe and effective as a treatment for patients with degenerative and traumatic lumbosacral pathology. Spinopelvic fixation provides improved soft tissue coverage and fewer hardware complications at minimum of 1 year follow up. This case series demonstrates a novel surgical technique for spinopelvic fixation in the setting of numerous spinal pathologies. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: This surgical technique is less technically challenging than current approaches, minimizes radiation exposure, and obviates the need for horizontal connector rods. In addition, in highly destabilizing pathologies, this technique also allows for multiple screw placement within the ilium, while maintaining the ability to connect to a single rod construct. This technique is safe, technically approachable, and broadly applicable to an array of spinopelvic pathologies.

A transpedicular approach to complex ventrally situated thoracic intradural extramedullary tumors: technique, indications, and multiinstitutional case series.

OBJECTIVE: Ventrally situated thoracic intradural extramedullary tumors are surgically challenging and difficult to access, and they may be complicated by extensive adhesions and calcifications. Selecting an approach for adequate ventral access is key to complete resection and optimization of outcomes. The authors present a case series of patients who underwent resection of ventral thoracic intradural extramedullary tumors and discuss indications and considerations for this technique. Additionally, they describe the use of a posterolateral transpedicular approach for resection of ventral thoracic intradural extramedullary tumors compared with other techniques, and they summarize the literature supporting its application. METHODS: From May 2017 to August 2020, 5 patients with ventral thoracic intradural extramedullary tumors underwent resection at one of the two academic institutions. RESULTS: Patient ages ranged from 47 to 75 (mean 63.4) years. All tumors were diagnosed as meningiomas or schwannomas by histological examination. Three of the 5 patients had evidence of partial or extensive tumor calcification. Four of the 5 patients underwent an initial posterolateral transpedicular approach for resection, with positive radiographic and clinical outcomes from surgery. One patient initially underwent an unsuccessful traditional direct posterior approach and required additional resection 2 years later after interval disease progression. There were no postoperative wound infections, CSF leaks, or other complications related to the transpedicular approach. CONCLUSIONS: Posterolateral transpedicular tumor resection is a safe technique for the treatment of complex ventrally situated thoracic intradural extramedullary tumors compared with the direct posterior approach. Anecdotally, this approach appears to be particularly beneficial in patients with calcified tumors.

Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.

Over 21,000 women are diagnosed with ovarian cancer (OC) in the United States each year and over half that number succumb to this disease annually, often due to recurrent disease. A deeper understanding of the molecular events associated with recurrent disease is needed to identify potential targets. Using genome-scale DNA methylation and gene expression data for 16 matched primary-recurrent advanced stage serous epithelial OCs, we discovered that Claudin-1 (CLDN1), a tight junction protein, shows a stronger correlation between expression and methylation in recurrent versus primary OC at multiple CpG sites (R= -0.47 to -0.64 versus R= -0.32 to -0.57, respectively). An independent dataset showed that this correlation is stronger in tumors from short-term (<3y) survivors than in tumors from long-term (>7y) survivors (R= -0.41 to -0.46 versus R= 0.06 to -0.19, respectively). The presence of this inverse correlation in short-term survivors and recurrent tumors suggests an important role for this relationship and potential predictive value for disease prognosis. CLDN1 expression increased following pharmacologic inhibition of DNA methyltransferase activity (p< 0.001), thus validating the role of methylation in CLDN1 gene inhibition. CLDN1 knockdown enhanced chemosensitivity and suppressed cell proliferation, migration, and wound healing (p< 0.05). Stable CLDN1 knockdown in vivo resulted in reduced xenograft tumor growth but did not reach significance. Our results indicate that the relationship between CLDN1 methylation and expression plays an important role in OC aggressiveness and recurrence.

Targeting Dormant Ovarian Cancer Cells In Vitro and in an In Vivo Mouse Model of Platinum Resistance.

Spheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers. Of 12 cell lines with increased anchorage-independent growth, 8 formed spheroids under serum-free culture conditions. Spheroids showed reduced proliferation (P < 0.0001) and Ki-67 immunostaining (8% vs. 87%) relative to monolayer cells. Spheroid formation was associated with increased expression of mitochondrial pathway genes (P ≤ 0.001) from Affymetrix HT U133A gene expression data. UCN-01, a kinase inhibitor/mitochondrial uncoupler that has been shown to lead to Puma-induced mitochondrial apoptosis as well as ATP synthase inhibitor oligomycin, demonstrated effectiveness against spheroids, whereas spheroids were refractory to cisplatin and paclitaxel. By live in vivo imaging, ovarian cancer xenograft tumors were reduced after primary treatment with carboplatin. Continued treatment with carboplatin was accompanied by an increase in tumor signal, whereas there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or oltipraz. Taken together, our findings suggest that genes involved in mitochondrial function in spheroids may be an important therapeutic target in preventing disease recurrence.