Outpatient Opioid Prescribing Habits in Pediatric Patients With Bone Sarcomas After Undergoing Primary Tumor Resection.

BACKGROUND: The majority of children with bone sarcomas experience pain. Opioids remain the mainstay treatment of cancer-related pain in children. The patterns of outpatient opioid prescription after surgery for primary bone sarcomas remains unknown. The purpose of this study is to evaluate the patterns of outpatient opioid prescription in patients with bone sarcomas after resection of the primary tumor, and to assess for factors that may lead to increased opioid dosing in these patients. METHODS: A retrospective chart review of 28 patients with bone sarcomas undergoing primary tumor resection was performed. Demographic, medical, surgical, and pharmacological data was collected from all patients. The total morphine milligram equivalents (MMEs) prescribed after patient discharge were compared at 30-day intervals. The MMEs were then stratified by tumor location, presence of metastasis at time of surgery, and preoperative opioid use. Independent predictors of increased 30-day and total 120-day opioid utilization were evaluated. RESULTS: Patients with preoperative opioid use were prescribed significantly more opioids in every 30-day postoperative interval and for the 120-day total. When stratified by tumor location, patients with primary tumors in the pelvis had significantly greater postoperative opioid utilization when compared with patients with tumors located in the lower and upper extremities during postoperative days 61 to 90 (5970 vs. 1060.4 and 0 MMEs, respectively, P=0.048) and during postoperative days 91 to 120 (6450 vs. 829.6 and 0 MMEs, respectively, P=0.015). Older age, diagnosis of osteosarcoma, increased length of stay postoperatively and presence of metastases were associated with a higher 30-day postoperative opioid utilization. CONCLUSION: Multiple factors were associated with increased opioid use including preoperative opioid use, longer postoperative stay in the hospital, metastatic disease, and primary sarcomas in the pelvis. The patient's sex, body mass index, race, type of insurance, type of surgery performed, reoperation during the same admission and use of nonopioid adjuvants had no effect on opioid use. The results of this study can be used to stratify the average opioid requirement of pediatric patients undergoing primary bone sarcoma resection. LEVEL OF EVIDENCE: Level IV.

Comparison of forces generated using compression plating versus a magnetic lengthening nail in a sawbones femur model.

BACKGROUND: The purpose of this study is to compare compression generated by a Precice magnetic lengthening intramedullary nail and a 5.0 mm limited contact dynamic compression plate. METHODS: Transverse osteotomy sites were created in the femoral shaft of ten Sawbones fourth generation composite femurs. Antegrade 10-degree trochanteric Precice nails and 8-hole, 5.0 mm plates were used for fixation. The plates were compressed by placing a neutral screw and three eccentrically drilled compression screws on alternating sides of the osteotomy. Average compression and distribution of compression were compared, and P-values <0.05 were considered statistically significant. FINDINGS: The Precice nail generated an average of 2.38 megapascal across the osteotomy sites. The plate generated an average of 0.70 megapascal (P < 0.001) with the initial compression screw, 0.93 megapascal (P < 0.001) after the second screw, and 1.04 megapascal (p < 0.001) after the final screw. The distribution of compression was assessed utilizing a polar transformation to compare pressure values. We found that the distribution of compression was more circumferentially uniform in the Precice nail group (P = 0.046). INTERPRETATION: This study demonstrates that an electromagnetic intramedullary device is capable of generating significantly higher compression, in a more uniform distribution, than a 5.0 mm limited contact dynamic compression plate in a Sawbones model. The results indicate that electromagnetic intramedullary nail systems may be an ideal alternative to compression plating for treatment of at-risk fractures, nonunions, delayed unions, and intercalary allograft reconstruction.

Bupivacaine and Lidocaine Induce Apoptosis in Osteosarcoma Tumor Cells.

BACKGROUND: Osteosarcoma is the most common type of bone cancer in adolescents. There have been no significant improvements in outcomes since chemotherapy was first introduced. Bupivacaine and lidocaine have been shown to be toxic to certain malignancies. This study evaluates the effect of these medications on two osteosarcoma cell lines. QUESTIONS/PURPOSES: (1) Does incubation of osteosarcoma cells with bupivacaine or lidocaine result in cell death? (2) Does this result from an apoptotic mechanism? (3) Is a specific apoptotic pathway implicated? METHODS: Two cell lines were chosen to account for the inherent heterogeneity of osteosarcoma. UMR-108 is a transplantable cell line that has been used in multiple studies as a primary tumor. MNNG/HOS has a high metastatic rate in vivo. Both cell lines were exposed bupivacaine (0.27, 0.54, 1.08, 2.16, 4.33 and 8.66 mM) and lidocaine (0.66, 1.33, 5.33, 10.66, 21.32 and 42.64 mM) for 24 hours, 48 hours, and 72 hours. These concentrations were determined by preliminary experiments that found the median effective dose was 1.4 mM for bupivacaine and 7.0 mM for lidocaine in both cell lines. Microculture tetrazolium and colony formation assay determined whether cell death occurred. Apoptosis induction was evaluated by phase-contrast micrographs, flow cytometry, DNA fragmentation and reactive oxygen species (ROS). The underlying pathways were analyzed by protein electrophoresis and Western blot. All testing was performed in triplicate and compared with pH-adjusted controls. Quantitative results were analyzed without blinding. RESULTS: Both medications caused cell death in a dose- and time-dependent manner. Exposure to bupivacaine for 24 hours reduced viability of UMR-108 cells by 6 ± 0.75% (95% CI 2.9 to 9.11; p = 0.01) at 1.08 mM and 89.67 ± 1.5% (95% CI 82.2 to 95.5; p < 0.001) at 2.16 mM. Under the same conditions, MNNG/HOS viability was decreased in a similar fashion. After 24 hours, the viability of UMR-108 and MNNG/HOS cells exposed to 5.33 mM of lidocaine decreased by 25.33 ± 8.3% (95% CI 2.1 to 48.49; p = 0.03) and 39.33 ± 3.19% (95% CI 30.46 to 48.21; p < 0.001), respectively, and by 90.67 ± 0.66% (95% CI 88.82 to 92.52; p < 0.001) and 81.6 ± 0.47% (95% CI 79.69 to 82.31; p < 0.001) at 10.66 mM, respectively. After 72 hours, the viability of both cell lines was further reduced. Cell death was consistent with apoptosis based on cell morphology, total number of apoptotic cells and DNA fragmentation. The percentage increase of apoptotic UMR-108 and MNNG/HOS cells confirmed by Annexin-V positivity compared with controls was 21.3 ± 2.82 (95% CI 16.25 to 26.48; p < 0.001) and 21.23 ± 3.23% (95% CI 12.2 to 30.2; p = 0.003) for bupivacaine at 1.08 mM and 25.15 ± 4.38 (95% CI 12.9 to 37.3; p = 0.004) and 9.11 ± 1.74 (95% CI 4.35 to 13.87; p = 0.006) for lidocaine at 5.33 mM. The intrinsic apoptotic pathway was involved as the expression of Bcl-2 and survivin were down-regulated, and Bax, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase-1 were increased. ROS production increased in the UMR-108 cells but was decreased in the MNNG/HOS cells. CONCLUSION: These findings provide a basis for evaluating these medications in the in vivo setting. Studies should be performed in small animals to determine if clinically relevant doses have a similar effect in vivo. In humans, biopsies could be performed with standard doses of these medications to see if there is a difference in biopsy tract contamination on definitive resection. CLINICAL RELEVANCE: Bupivacaine and lidocaine could potentially be used for their ability to induce and enhance apoptosis in local osteosarcoma treatment. Outcome data when these medications are used routinely during osteosarcoma treatment can be evaluated compared with controls. Further small animal studies should be performed to determine if injection into the tumor, isolated limb perfusion, or other modalities of treatment are viable.

Secondary Chondrosarcoma Arising from the Proximal Fibula Presenting as Sciatica.

INTRODUCTION: Secondary chondrosarcoma is a rare entity arising from a pre-existing cartilaginous lesion. Transformation of an osteochondroma to a chondrosarcoma occurs in <1% of cases. Sciatica is a common problem that can cause significant pain, weakness, and numbness. CASE REPORT: A 36-year-old male presented to the Orthopedic Oncology Service after being treated for sciatica for 3 years. Magnetic resonance imaging of the lumbar spine demonstrated degenerative disc disease with mild inferior foraminal narrowing at L5-S1. He had undergone multiple epidural steroid injections without improvement in his symptoms. A chondrosarcoma encasing the peroneal nerve was found arising from an underlying osteochondroma in the proximal fibula. The patient underwent resection of the tumor which included resection of the peroneal nerve. Five years after resection, the patient is disease free and uses an ankle-foot orthosis for ambulation. CONCLUSION: This case demonstrates the importance of evaluating a patient with peripheral nerve symptoms for a lesion within the involved extremity along the entire length of the nerve. Extraspinal lesions can compress peripheral nerves and cause radicular symptoms. Timely treatment is important to prevent malignant transformation or worsening of the tumor as well as to provide better functional outcome.

Antiproliferative effect of bupivacaine on patient-derived sarcoma cells.

Sarcomas are rare tumors with limited treatment options. Although chemotherapy is standard for certain subtypes, overall survival has not improved in several decades. Bupivacaine has been shown to induce apoptosis and prevent cell growth in multiple different types of malignancies but has not been studied in sarcoma. The current study evaluated the effects of bupivacaine on multiple patient-derived sarcoma cells and a commercial sarcoma cell line. Multiple patient-derived sarcoma cell subtypes and a commercial synovial cell sarcoma cell line were exposed to bupivacaine for different durations and at different concentrations. The patient-derived cells included a high-grade conventional osteosarcoma, a high-grade undifferentiated pleomorphic sarcoma of bone, and a high-grade synovial sarcoma. Flow cytometry and an MTT assay were used to evaluate whether a treatment effect was observed. Treatment of all the subtypes of sarcomas in this study with bupivacaine demonstrated a time- and dose-dependent increase in apoptosis and decrease in cell viability. A cell viability assay demonstrated that the IC50 was between 0.04 and 0.05% and that the treatment effect occurred at clinically relevant doses in vitro. Bupivacaine was toxic to both the patient-derived cells and the commercial cell line at doses commonly used in the clinical setting. These findings provide a foundation for further in vivo studies to evaluate whether these effects will translate to the clinical setting. Although further research is necessary, bupivacaine shows promise as not only an adjunct for pain management but as a treatment modality for sarcoma.

Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line In Vitro.

Recurrence or metastasis remains the major cause of poor prognosis and mortality in Osteosarcoma patients. Therefore, development of more effective therapeutic approaches is required. We showed that indomethacin, significantly induces apoptosis in MNNG/HOS cell line, which was confirmed by morphological changes, increased Annexin-V + cells and nuclear fragmentation. Apoptosis was accompanied by increased cleavage of caspase-3 and PARP, suggesting activation of caspase-dependent cell death. Indomethacin significantly decreased the expression of ß-catenin, a key player in tumor metastasis. These results indicate that indomethacin may have the potential to be used as neoadjuvant or adjuvant treatment; however, additional studies are required.

Short tau inversion recovery magnetic resonance imaging for staging and screening in myxoid liposarcoma.

PURPOSE: Myxoid liposarcoma has a propensity to metastasize to bone. MRI is the preferred modality for detecting bone disease. We evaluated multiple MRI sequences to determine an optimal screening method. METHODS: Whole body MRI was performed on all patients. The number and locations of metastases found by imaging and round cell component of the sites sampled were evaluated. RESULTS: We found a total of 68 osseous lesions. Whole body MRI utilizing STIR only sequences decreased imaging time by 83.6% and demonstrated the lesions the best. CONCLUSIONS: STIR sequences can be exclusively used during staging and screening of myxoid liposarcoma.

Development of multifocal extra-abdominal desmoid fibromatosis after surgical resection.

Multifocal fibromatosis is a rare entity. We report on two cases where multifocal disease developed after surgical resection. Chronic inflammation and repetitive trauma may be considered a risk factor for developing multifocal disease.