Intravenous tranexamic acid reduces complications following surgical treatment of pathologic fractures of the lower extremity.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the postoperative complications associated with administering intravenous (IV) tranexamic acid (TXA) in patients undergoing surgical fixation for neoplastic pathologic fractures of the lower extremities. METHODS: Patients ≥18 years old who underwent surgical intervention for neoplastic pathologic lower extremity fractures from 2015 to 2021 were identified using the Premier Healthcare Database. This cohort was divided by TXA receipt on the index surgery day. Patient demographics, hospital factors, patient comorbidities, and 90-day complications were assessed and compared between the cohorts. RESULTS: From 2015 to 2021, 4497 patients met inclusion criteria (769 TXA[+] and 3728 TXA[-]). Following propensity score matching, patients who received TXA had a significantly shorter length of stay than those who did not (7.6 ± 7.3 days vs. 9.0 ± 15.2, p = 0.036). Between the two cohorts, there were no significant differences in comorbidities. Regarding differences in postoperative complications, TXA(+) patients had significantly decreased odds of deep vein thrombosis (DVT) (1.87% vs. 5.46%; odds ratio [OR]:0.33; 95% confidence interval: 0.17-0.62; p = 0.001). CONCLUSION: Administration of IV TXA may be associated with a decreased risk of postoperative DVT without an increased risk of other complications. Orthopedic surgeons should consider the utilization of IV TXA in patients treated surgically for neoplastic pathologic fractures of the lower extremity.

Medicare Advantage in Soft Tissue Sarcoma May Be Associated with Worse Patient Outcomes.

Medicare Advantage healthcare plans may present undue impediments that result in disparities in patient outcomes. This study aims to compare the outcomes of patients who underwent STS resection based on enrollment in either traditional Medicare (TM) or Medicare Advantage (MA) plans. The Premier Healthcare Database was utilized to identify all patients ≥65 years old who underwent surgery for resection of a lower-extremity STS from 2015 to 2021. These patients were then subdivided based on their Medicare enrollment status (i.e., TM or MA). Patient characteristics, hospital factors, and comorbidities were recorded for each cohort. Bivariable analysis was performed to assess the 90-day risk of postoperative complications. Multivariable analysis controlling for patient sex, as well as demographic and hospital factors found to be significantly different between the cohorts, was also performed. From 2015 to 2021, 1858 patients underwent resection of STS. Of these, 595 (32.0%) had MA coverage and 1048 (56.4%) had TM coverage. The only comorbidities with a significant difference between the cohorts were peripheral vascular disease (p = 0.027) and hypothyroidism (p = 0.022), both with greater frequency in MA patients. After controlling for confounders, MA trended towards having significantly higher odds of pulmonary embolism (adjusted odds ratio (aOR): 1.98, 95% confidence interval (95%-CI): 0.58-6.79), stroke (aOR: 1.14, 95%-CI: 0.20-6.31), surgical site infection (aOR: 1.59, 95%-CI: 0.75-3.37), and 90-day in-hospital death (aOR 1.38, 95%-CI: 0.60-3.19). Overall, statistically significant differences in postoperative outcomes were not achieved in this study. The authors of this study hypothesize that this may be due to study underpowering or the inability to control for other oncologic factors not available in the Premier database. Further research with higher power, such as through multi-institutional collaboration, is warranted to better assess if there truly are no differences in outcomes by Medicare subtype for this patient population.

Complications of cryoprobe cryoablation as a surgical adjuvant for the treatment of metastatic carcinoma to bone, benign bone tumors, and soft tissue tumors: A series of 148 patients.

BACKGROUND AND OBJECTIVE: This study describes the complication profile of modern cryoablation utilizing probes as an adjuvant during open surgical treatment of orthopedic tumors. METHODS: A retrospective, single-surgeon study was performed for patients receiving cryoprobe cryoablation. Demographic information, malignancy-related and operative details, and clinical courses were collected. Outcomes assessed included rates of complications, recurrence, and correlations between the number of probes or cryoablation cycles performed. RESULTS: In this 148-patient study, 67.6% had metastatic carcinoma to bone, 27.7% had benign bone tumors, and 4.7% had soft tissue tumors. An average of 3.4 ± 1.7 cryoablation probes were utilized and 1.7 ± 0.6 freezing cycles were performed. The overall cohort aggregate complication rate was 16.9%. These complications included postoperative fracture (3.4%), nerve palsy (2.7%), wound complications (7.4%), and infection (3.4%). The number of cycles and probes was significantly correlated with the incidence of aggregate complications in the overall cohort (Pearson = 0.162, p = 0.049) and metastatic bone cohort (Pearson = 0.222, p = 0.027). There were 13 recurrences. CONCLUSION: This study describes the complication rates involving cryoablation probes used as surgical adjuvants. Greater probe number usage was correlated with increased aggregate complications in patients with metastatic disease to bone; meanwhile, more treatment cycles were associated with increased aggregate complications in the overall cohort.

Prevalence of primary malignant tumours, rates of pathological fracture, and mortality in the setting of metastatic bone disease.

Aims: The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. Methods: The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures. Results: In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. Conclusion: This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease.

Clinical outcomes of cemented distal femur replacements with all-polyethylene tibial components for oncologic indications.

BACKGROUND: Endoprosthetic distal femoral replacement (DFR) is a well-established salvage procedure following resection of malignant tumors within the distal femur. Use of an all-polyethylene tibial (APT) component is cost-effective and avoids failure due to locking-mechanism issues and backside wear, but limits modularity and the option for late liner exchange. Due to a paucity of literature we sought to answer three questions: (1) What are the most common modes of implant failure for patients undergoing cemented DFR with APT for oncologic indications? (2) What is the survivorship, rate of all-cause reoperation, and rate of revision for aseptic loosening of these implants? And (3) Is there a difference in implant survivorship or patient demographics between cemented DFRs with APT performed as a primary reconstruction vs those performed as a revision procedure? AIM: To assess outcomes of cemented DFRs with APT components used for oncologic indications. METHODS: After Institutional Review Board approval, a retrospective review of consecutive patients who underwent DFR between December 2000 to September 2020 was performed using a single-institutional database. Inclusion criteria consisted of all patients who underwent DFR with a GMRS® (Global Modular Replacement System, Stryker, Kalamazoo, MI, United States) cemented distal femoral endoprosthesis and APT component for an oncologic indication. Patients undergoing DFR for non-oncologic indications and patients with metal-backed tibial components were excluded. Implant failure was recorded using Henderson's classification and survivorship was reported using a competing risks analysis. RESULTS: 55 DFRs (55 patients) with an average age of 50.9 ± 20.7 years and average body mass index of 29.7 ± 8.3 kg/m2 were followed for 38.8 ± 54.9 mo (range 0.2-208.4). Of these, 60.0% were female and 52.7% were white. The majority of DFRs with APT in this cohort were indicated for oncologic diagnoses of osteogenic sarcoma (n = 22, 40.0%), giant cell tumor (n = 9, 16.4%), and metastatic carcinoma (n = 8, 14.6%). DFR with APT implantation was performed as a primary procedure in 29 patients (52.7%) and a revision procedure in 26 patients (47.3%). Overall, twenty patients (36.4%) experienced a postoperative complication requiring reoperation. The primary modes of implant failure included Henderson Type 1 (soft tissue failure, n = 6, 10.9%), Type 2 (aseptic loosening, n = 5, 9.1%), and Type 4 (infection, n = 6, 10.9%). There were no significant differences in patient demographics or rates of postoperative complications between the primary procedure and revision procedure subgroups. In total, 12 patients (21.8%) required a revision while 20 patients (36.4%) required a reoperation, resulting in three-year cumulative incidences of 24.0% (95%CI 9.9%-41.4%) and 47.2% (95%CI 27.5%-64.5%), respectively. CONCLUSION: This study demonstrates modest short-term survivorship following cemented DFR with APT components for oncologic indications. Soft tissue failure and endoprosthetic infection were the most common postoperative complications in our cohort.

Postoperative Complication and Reoperation Rates Following Resection of Soft Tissue vs. Bone Malignancies Based on Anatomic Location in the Inpatient Setting.

Introduction: Surgical excisions of upper and lower extremity malignancies are increasing annually, due in part to the rising incidence of sarcomas. The purpose of this study is to compare readmissions, reoperation rate, and complications following surgical excision of soft/connective tissue vs bone malignancies of the upper and lower extremities. Methods: The Nationwide Readmissions Database (NRD) was queried from 2016-2017 to conduct a retrospective analysis of 16,435 patients diagnosed with malignant neoplasms of the long bone (ULLB, n = 1,433) and soft tissue (ULST, n = 2,049) of the upper limb and malignant neoplasms of the long bone (LLLB, n = 5,422) and soft tissue (LLST, n = 7,531) of the lower limb. Patients who underwent surgical excision of their neoplasms were included. Binomial multivariate logistic regression was used to compare complications, nonelective readmission rates, and reoperation rates between the two groups at 30 and 90 days. Results: Average age of the ULST group was 61.88, with 36% female. Average age of the ULLB group was 44.97, with 41.90% female. Average age of the LLST group was 60.96, with 46.90% female. Average age of the LLLB group was 43.09, with 42.60% female. The ULST group had lower odds of readmission within 30 days (p=0.263), which became significant within 90 days of surgery (p=0.045). The LLST group had significantly higher odds of infection, reoperation within 30 to 90 days of the index surgery compared to the LLLB group (p < 0.0001). The LLST group had significantly lower odds of readmission within 30 (p=0.04) and 90 days (p=0.015) of the index surgery. Conclusion: Patients in the ULST group had significantly lower odds of 90-day readmission compared to the ULLB group. There were also significantly lower odds of 30- and 90-day readmission in the LLST group compared to the LLLB group. However, the LLST group had significantly higher odds of infection and reoperation within 30 and 90 days compared to the LLLB group.

Timing of treatment in osteosarcoma: challenges and perspectives - a scoping review.

BACKGROUND: The timing of events in the management of osteosarcoma may be critical for patient survivorship; however, the prognostic value of factors such as onset of symptoms or initiation of therapy in these patients has not been studied. This study sought to review the literature reporting treatment of osteosarcoma to determine the utility of event timing as a prognostic indicator. Due to significant heterogeneity in the literature, this study was conducted as a scoping review to assess the current state of the literature, identify strengths and weaknesses in current reporting practices, and to propose avenues for future improvement. MAIN BODY: This review screened 312 peer-reviewed studies of osteosarcoma in any anatomic location published in an English journal for reporting of an event timing metric of any kind in a population of 6 or more. Thirty-seven studies met inclusion/exclusion criteria and were assessed for level of evidence, quality, and event timing metric. Reviewers also collated: publication year, population size, population age, tumor site, tumor type, surgical treatment, and adjuvant medical treatment. Extracted event timing data were further characterized using nine standardized categories to enable systematic analysis. The reporting of event timing in the treatment of osteosarcoma was incomplete and heterogenous. Only 37 of 312 (11.9%) screened studies reported event timing in any capacity. The period between patient-reported symptom initiation and definitive diagnosis was the most reported (17/37, 45.9%). Symptom duration was the second most reported period (10/37, 27.0%). Event timing was typically reported incidentally and was never rigorously incorporated into data analysis or discussion. No studies considered the impact of event timing on a primary outcome. The six largest studies were assessed in detail to identify pearls for future researchers. Notable shortcomings included the inadequate reporting of the definition of an event timing period and the pooling of patients into poorly defined timing groups. CONCLUSIONS: Inconsistent reporting of event timing in osteosarcoma treatment prevents the development of clinically useful conclusions despite evidence to suggest event timing is a useful prognostic indicator. Consensus guidelines are necessary to improve uniformity and utility in the reporting of event timing.

PD-1 inhibition therapy for advanced cutaneous squamous cell carcinoma: a retrospective analysis from the University of Southern California.

PURPOSE: Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy. METHODS: We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed. RESULTS: Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes. CONCLUSION: PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.

Risk Factors for Wound Complications After Soft Tissue Sarcoma Resection.

ABSTRACT: Soft tissue sarcomas are a heterogenous group of malignant tumors that represent approximately 1% of adult malignancies. Although these tumors occur throughout the body, the majority involved the lower extremity. Management may involve amputation but more commonly often includes wide local resection by an oncologic surgeon and involvement of a plastic surgeon for reconstruction of larger and more complex defects. Postoperative wound complications are challenging for the surgeon and patient but also impact management of adjuvant chemotherapy and radiation therapy. To explore risk factors for wound complications, we reviewed our single-institution experience of lower-extremity soft tissue sarcomas from April 2009 to September 2016. We identified 127 patients for retrospective review and analysis. The proportion of patients with wound complications in the cohort was 43.3%. Most notably, compared with patients without wound complications, patients with wound complications had a higher proportion of immediate reconstruction (34.5% vs 15.3%; P = 0.05) and a marginally higher proportion who received neoadjuvant radiation (30.9% vs 16.7%; P = 0.06).

Bizarre parosteal osteochondromatous proliferation: Rare case affecting distal ulna and review of literature.

Bizarre parosteal osteochondromatous proliferation (BPOP) or Nora's lesion, is a rare benign surface-based bone lesion most commonly involving the tubular bones of hands and feet. We report an unusual case of BPOP affecting the distal ulna in a 22-year-old man who presented with a painless wrist mass following injury and was successfully treated with surgical resection. We focus on multi-modality imaging, histopathology, and differential diagnosis (including osteochondroma, florid reactive periostitis, myositis ossificans, and surface-type osteosarcoma), as well as a review of the literature regarding recent concepts on etiology and evolution, spectrum of imaging characteristics and diagnostic overlap, histopathology, as well as treatment options.

Solid aneurysmal bone cyst of the humerus mimics metastasis or brown tumor.

Solid aneurysmal bone cyst (ABC) is a rare subtype of ABC that most commonly involves the small bones of the hands or feet. We present a case of a solid ABC of the distal humerus in a 52-year-old man with a history of chronic kidney disease and renal cell carcinoma. On imaging with plain radiographs, CT, and MRI, this expansile lucent lesion with solid internal enhancement had an appearance that overlapped with metastasis or brown tumor of hyperparathyroidism. On 18F-FDG PET-CT, this lesion was hypermetabolic with an SUVmax of 9.9. Only 37 cases of solid ABC have previously been reported to involve the long bones in the literature, and only 4 in the humerus. We review the clinical, imaging, and histopathological findings and differential diagnosis of solid ABC, and highlight the usefulness of identifying the USP6 gene rearrangement on FISH to distinguish this lesion from other lesions with secondary ABC formation.

Giant cell tumor: rapid recurrence after cessation of long-term denosumab therapy.

We report a case of rapid recurrence of a giant cell tumor (GCT) of the distal radius in a 24-year-old woman following the cessation of long-term denosumab therapy. GCT of bone is a histologically benign tumor with multinucleated giant cells on a background of mononuclear giant cells usually presenting as a well-defined epi-metaphyseal lytic lesion without sclerotic margins. Denosumab, a monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), has proven to be an effective neoadjuvant treatment for GCT. The tumor in this case had demonstrated a good response with sustained control for over 2 years while on denosumab therapy. However, within 2 months of cessation of therapy, the tumor demonstrated rapid recurrence and progression with growth, osteolysis, and increased soft tissue component. Despite reinitiating denosumab therapy, there was progressive tumor growth and destruction, ultimately necessitating below-the-elbow amputation. This case illustrates the need for maintenance of denosumab therapy for GCT of bone or definitive surgical treatment prior to its cessation.

Prognostic value of necrosis after neoadjuvant therapy for soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: While treatment-induced tissue necrosis is a well-documented predictor of patient survival in malignant bone tumors, its prognostic value in soft tissue sarcomas is controversial. A prior study from our institution did not find a prognostic value to tumor necrosis. We analyze a more extensive database of high-grade soft tissue sarcomas treated with neoadjuvant chemotherapy, radiation therapy, or both to re-evaluate if the degree of tumor necrosis alone can be used as a predictive factor for local recurrence, metastasis, and disease-specific survival. METHODS: Two hundred and seven patients with high-grade extremity soft tissue sarcoma received neoadjuvant chemotherapy and/or radiation therapy and wide excision. Tumor treatment response was determined by histopathologic analysis, and patients were followed for local recurrence, metastasis, or death. RESULTS: Tumor necrosis ≥ 90% correlates with improved disease-free survival with univariate analysis, but this does not reach statistical significance on multivariate analysis. Age and tumor volume were found to be the only independent predictors of disease-free survival on multivariate analysis. CONCLUSIONS: There is insufficient evidence to support the use of necrosis to prognosticate survival and alter chemoradiation regimens in high grade soft tissue sarcomas of the extremity. Larger studies are needed to definitively address the prognostic value of necrosis. LEVEL OF EVIDENCE: Level II, Prognostic

Early clinical and radiographic results of minimally invasive anterior approach hip arthroplasty.

We present a retrospective review of the early results and complications in a series of 35 consecutive patients with 43 total hip arthroplasties performed through an anterior muscle sparing minimally invasive approach. We found the early complication rates and radiographic outcomes comparable to those reported from arthroplasties performed via traditional approaches. Complications included dislocation (2%), femur fracture (2%), greater trochanteric fracture (12%), postoperative periprosthetic intertrochanteric fracture (2%), femoral nerve palsy (5%), hematoma (2%), and postoperative iliopsoas avulsion (2%). Radiographic analysis revealed average cup anteversion of 19.6° ± 6.6, average cup abduction angle of 48.4° ± 7, stem varus of 0.9° ± 2, and a mean leg length discrepancy of 0.7 mm. The anterior approach to the hip is an attractive alternative to the more traditional approaches. Acceptable component placement with comparable complication rates is possible using a muscle sparing technique which may lead to faster overall recovery.

Clavicular eosinophilic granuloma causing adult shoulder pain.

Though rarely reported, neoplasms of the clavicle occur, and their symptoms can be mistaken for more common shoulder conditions. We present the case of a benign clavicular neoplasm, rarely seen in adults, presenting with pain, and eventual pathologic fracture in a 49 year-old. A 49 year-old male firefighter underwent arthroscopic rotator cuff repair for shoulder pain after magnetic resonance imaging revealed supraspinatus tendon tear. The patient's pain persisted after surgery, and was described as routine until he developed severe pain after minor blunt trauma. A local Emergency Room performed the first x-rays, which revealed a pathologic fracture of the distal clavicle through a destructive lesion. The patient was referred to an orthopedic oncologist, who performed incisional biopsy, which initially diagnosed osteomyelitis. The patient was subsequently taken to surgery for debridement. Pathology then yielded the diagnosis of eosinophilic granuloma. The patient was taken back to surgery for formal curettage with open reduction and internal fixation. The patient's pain resolved, the pathologic fracture fully healed, and the patient returned to full time work as a firefighter. Though workup for common shoulder conditions often identifies incidental benign lesions of bone, the converse can be true. Persistent pain despite intervention should raise concern for further investigation. An x-ray alone can reveal a destructive bone lesion as the source of shoulder pain.

Limb-sparing surgery for distal femoral and proximal tibial bone lesions: imaging findings with intraoperative correlation.

OBJECTIVE: Our purpose is to present normal and abnormal imaging findings associated with endoprosthetic reconstruction after limb-salvage surgery. CONCLUSION: Endoprosthetic reconstruction varies with the location and size of the tumor, implant designs, and complications. Radiologists need to be aware of associated imaging findings seen in postoperative infection, tumor recurrence, and hardware failure. With a thorough understanding of the normal postoperative radiographic findings after complex reconstructions, subsequent abnormalities are readily identified and timely diagnosis can be obtained.

A meta-analysis of osteosarcoma outcomes in the modern medical era.

Four decades ago, specialized chemotherapy regimens turned osteosarcoma, once considered a uniformly fatal disease, into a disease in which a majority of patients survive. Though significant survival gains were made from the 1960s to the 1980s, further outcome improvements appear to have plateaued. This study aims to comprehensively review all significant, published data regarding osteosarcoma and outcome in the modern medical era in order to gauge treatment progress. Our results indicate that published survival improved dramatically from 1960s to 1980s and then leveled, or in some measures decreased. Recurrence rates decreased in the 1970s and then leveled. In contrast, published limb salvage rates have increased significantly every recent decade until the present. Though significant gains have been made in the past, no improvement in published osteosarcoma survival has been seen since 1980, highlighting the importance of a new strategy in the systemic management of this still very lethal condition.

Moving beyond response criteria: new measures of success in the treatment of sarcomas.

There is an urgent need to develop new therapies for soft tissue sarcomas. Traditional cytotoxic therapies, such as doxorubicin and ifosfamide, have been the standard approach to this disease. However, newer paradigms are emerging that are less toxic while targeting dysregulated pathways, tumor hypoxia, and genetic translocations. These newer therapies require different measures of activity as standard response criteria may inaccurately measure their effectiveness. Serious consideration of select endpoints and measures of tumor response are crucial to make significant strides in the treatment of sarcomas. Current studies on soft tissue sarcomas are slowly abandoning response rates while employing progression-free survival and time to progression as improved endpoints. With time and data, our understanding of the relative activity of these agents will grow and lead to improved benefits for our patients.