Surgical Site Infection in Patients Managed with an Endoprosthesis for the Treatment of Cancer: Evaluation of Patient, Disease, and Index Surgical Factors.

BACKGROUND: Surgical site infection (SSI) after segmental endoprosthetic reconstruction in patients treated for oncologic conditions remains both a devastating and a common complication. The goal of the present study was to identify variables associated with the success or failure of treatment of early SSI following the treatment of a primary bone tumor with use of a segmental endoprosthesis. METHODS: The present study used the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) data set to identify patients who had been diagnosed with an SSI after undergoing endoprosthetic reconstruction of a lower extremity primary bone tumor. The primary outcome of interest in the present study was a dichotomous variable: the success or failure of infection treatment. We defined failure as the inability to eradicate the infection, which we considered as an outcome of amputation or limb retention with chronic antibiotic suppression (>90 days or ongoing therapy at the conclusion of the study). Multivariable models were created with covariates of interest for each of the following: surgery characteristics, cancer treatment-related characteristics, and tumor characteristics. Multivariable testing included variables selected on the basis of known associations with infection or results of the univariable tests. RESULTS: Of the 96 patients who were diagnosed with an SSI, 27 (28%) had successful eradication of the infection and 69 had treatment failure. Baseline and index procedure variables showing significant association with SSI treatment outcome were moderate/large amounts of fascial excision ≥1 cm2) (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.001), use of local muscle/skin graft (OR,11.88 [95% CI, 1.83 to 245.83]; p = 0.031), and use of a deep Hemovac (OR, 0.24 [95% CI, 0.05 to 0.85]; p = 0.041). In the final multivariable model, excision of fascia during primary tumor resection was the only variable with a significant association with treatment outcome (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.018). CONCLUSIONS: The results of this secondary analysis of the PARITY trial data provide further insight into the patient-, disease-, and treatment-specific associations with SSI treatment outcomes, which may help to inform decision-making and management of SSI in patients who have undergone segmental bone reconstruction of the femur or tibia for oncologic indications. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The stability of the hip after the use of a proximal femoral endoprosthesis for oncological indications: analysis of variables relating to the patient and the surgical technique.

AIMS: Instability of the hip is the most common mode of failure after reconstruction with a proximal femoral arthroplasty (PFA) using an endoprosthesis after excision of a tumour. Small studies report improved stability with capsular repair of the hip and other techniques, but these have not been investigated in a large series of patients. The aim of this study was to evaluate variables associated with the patient and the operation that affect post-operative stability. We hypothesised an association between capsular repair and stability. PATIENTS AND METHODS: In a retrospective cohort study, we identified 527 adult patients who were treated with a PFA for tumours. Our data included demographics, the pathological diagnosis, the amount of resection of the abductor muscles, the techniques of reconstruction and the characteristics of the implant. We used regression analysis to compare patients with and without post-operative instability. RESULTS: A total of 20 patients out of 527 (4%) had instability which presented at a mean of 35 days (3 to 131) post-operatively. Capsular repair was not associated with a reduced rate of instability. Bivariate analysis showed that a posterolateral surgical approach (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.02 to 0.86) and the type of implant (p = 0.046) had a significant association with reduced instability; age > 60 years predicted instability (OR 3.17, 95% CI 1.00 to 9.98). Multivariate analysis showed age > 60 years (OR 5.09, 95% CI 1.23 to 21.07), female gender (OR 1.73, 95% CI 1.04 to 2.89), a malignant primary bone tumour (OR 2.04, 95% CI 1.06 to 3.95), and benign condition (OR 5.56, 95% CI 1.35 to 22.90), but not metastatic disease or soft-tissue tumours, predicted instability, while a posterolateral approach (OR 0.09, 95% CI 0.01 to 0.53) was protective against instability. No instability occurred when a synthetic graft was used in 70 patients. CONCLUSION: Stability of the hip after PFA is influenced by variables associated with the patient, the pathology, the surgical technique and the implant. We did not find an association between capsular repair and improved stability. Extension of the tumour often dictates surgical technique; however, our results indicate that PFA using a posterolateral approach with a hemiarthroplasty and synthetic augment for soft-tissue repair confers the lowest risk of instability. Patients who are elderly, female, or with a primary benign or malignant bone tumour should be counselled about an increased risk of instability. Cite this article: Bone Joint J 2017;99-B:531-7.

Myogenic transcription factors regulate pro-metastatic miR-182.

Approximately 30% of patients with soft-tissue sarcoma die from pulmonary metastases. The mechanisms that drive sarcoma metastasis are not well understood. Recently, we identified miR-182 as a driver of sarcoma metastasis in a primary mouse model of soft-tissue sarcoma. We also observed elevated miR-182 in a subset of primary human sarcomas that metastasized to the lungs. Here, we show that myogenic differentiation factors regulate miR-182 levels to contribute to metastasis in mouse models. We find that MyoD directly binds the miR-182 promoter to increase miR-182 expression. Furthermore, mechanistic studies revealed that Pax7 can promote sarcoma metastasis in vivo through MyoD-dependent regulation of pro-metastatic miR-182. Taken together, these results suggest that sarcoma metastasis can be partially controlled through Pax7/MyoD-dependent activation of miR-182 and provide insight into the role that myogenic transcription factors have in sarcoma progression.

Internal fixation of radiation-induced pathological fractures of the femur has a high rate of failure.

We investigated the clinical outcome of internal fixation for pathological fracture of the femur after primary excision of a soft-tissue sarcoma that had been treated with adjuvant radiotherapy. A review of our database identified 22 radiation-induced fractures of the femur in 22 patients (seven men, 15 women). We noted the mechanism of injury, fracture pattern and any complications after internal fixation, including nonunion, hardware failure, secondary fracture or deep infection. The mean age of the patients at primary excision of the tumour was 58.3 years (39 to 86). The mean time from primary excision to fracture was 73.2 months (2 to 195). The mean follow-up after fracture fixation was 65.9 months (12 to 205). Complications occurred in 19 patients (86%). Nonunion developed in 18 patients (82%), of whom 11 had a radiological nonunion at 12 months, five a nonunion and hardware failure and two an infected nonunion. One patient developed a second radiation-associated fracture of the femur after internal fixation and union of the initial fracture. A total of 13 patients (59%) underwent 24 revision operations. Internal fixation of a pathological fracture of the femur after radiotherapy for a soft-tissue sarcoma has an extremely high rate of complication and requires specialist attention.

[Femur reconstruction using combined autologous fibula transfer and humeral allograft]. / Femurrekonstruktion mit kombiniertem autologem Fibulatransfer und Humerus-Allograft.

Wide resection far into the femoral metaphysis may be required to treat malignant bone tumors in the pediatric and adolescent patient population. Biological reconstruction using a free, vascularized fibular graft is a well-established surgical technique. A short remaining femoral medullary canal and a relatively small fibula diameter can make fixation of the vascularized bone transfer difficult. Stable fixation and short fusion times, however, can be achieved with the use of an additional humeral allograft and plate osteosynthesis.

Immunohistochemistry of the canine vomeronasal organ.

The canine's olfactory acuity is legendary, but neither its main olfactory system nor its vomeronasal system has been described in much detail. We used immunohistochemistry on paraffin-embedded sections of male and female adult dog vomeronasal organ (VNO) to characterize the expression of proteins known to be expressed in the VNO of several other mammals. Basal cell bodies were more apparent in each section than in rodent VNO and expressed immunoreactivity to anticytokeratin and antiepidermal growth factor receptor antibodies. The thin layer of neurone cell bodies in the sensory epithelium and axon fascicles in the lamina propria expressed immunoreactivity to neurone cell adhesion molecule, neurone-specific beta tubulin and protein gene product 9.5. Some neurones expressed growth-associated protein 43 (GAP43): and a number of those also expressed neurone-specific beta tubulin-immunoreactivity. Some axon fascicles were double labelled for those two proteins. The G-protein alpha subunits Gi and Go, involved in the signal transduction pathway, showed immunoreactivity in the sensory cell layer. Our results demonstrate that the canine vomeronasal organ contains a population of cells that expresses several neuronal markers. Furthermore, GAP43 immunoreactivity suggests that the sensory epithelium is neurogenic in adult dogs.

Immunohistochemistry of the canine vomeronasal organ.

The canine's olfactory acuity is legendary, but neither its main olfactory system nor its vomeronasal system has been described in much detail. We used immunohistochemistry on paraffin-embedded sections of male and female adult dog vomeronasal organ (VNO) to characterize the expression of proteins known to be expressed in the VNO of several other mammals. Basal cell bodies were more apparent in each section than in rodent VNO and expressed immunoreactivity to anticytokeratin and antiepidermal growth factor receptor antibodies. The thin layer of neurone cell bodies in the sensory epithelium and axon fascicles in the lamina propria expressed immunoreactivity to neurone cell adhesion molecule, neurone-specific beta tubulin and protein gene product 9.5. Some neurones expressed growth-associated protein 43 (GAP43): and a number of those also expressed neurone-specific beta tubulin-immunoreactivity. Some axon fascicles were double labelled for those two proteins. The G-protein alpha subunits Gi and Go, involved in the signal transduction pathway, showed immunoreactivity in the sensory cell layer. Our results demonstrate that the canine vomeronasal organ contains a population of cells that expresses several neuronal markers. Furthermore, GAP43 immunoreactivity suggests that the sensory epithelium is neurogenic in adult dogs.

Shuttle mission effects on glutamate receptor expression in the developing rodent spinal cord.

BACKGROUND: Within the mammalian central nervous system (CNS), glutamate receptors play a fundamental role in excitatory neurotransmission and synaptic plasticity. Studies of the neonatal cerebral cortex suggests that rearing environment can influence the dynamic patterns of glutamate receptor subunit expression during development. We examined this issue in the developing spinal cord, a well studied region of the CNS in which activity-dependent synaptic plasticity is known to occur. METHODS: We compared the abundance (by immunoblot analysis) and tissue distribution (by immunohistology) of glutamate receptor subunits in neonatal animals who participated in the Neurolab Space Shuttle mission. Flight animals were either postnatal day 8 or 13 at launch and spent the next 16 d in microgravity; tissues were recovered within 12 h of landing. Littermate control animals were reared on Earth at 1 G. RESULT: Using semi-quantitative immunoblot assays, no statistically significant differences were found in the overall abundance of any glutamate receptor subunit in the spinal cords of the two groups of animals. Similarly, immunohistological examination of spinal cords revealed no evidence for differences in the distribution of glutamate receptor subunits between the two groups of animals. CONCLUSIONS: These results indicate that the developmental regulation of glutamate receptor subunit expression in the spinal cord is not appreciably affected by the conditions associated with this space shuttle mission and prolonged rearing period in microgravity.