Modern Management of High-risk Soft Tissue Sarcoma With Neoadjuvant Chemoradiation: A Single-center Experience.

OBJECTIVE: Neoadjuvant chemoradiation (NA-CRT), followed by resection of high-risk soft tissue sarcoma (STS), may offer good disease control and toxicity outcomes. We report on a single institution's modern NA-CRT experience. MATERIALS AND METHODS: Delay to surgical resection, resection margin status, extent of necrosis, tumor cell viability, presence of hyalinization, positron emission tomography (PET)/computed tomography data, and treatment toxicities were collected. Using the Kaplan-Meier survival analysis, 5-year overall survival, disease-free survival, distant metastasis-free survival, and local control (LC) were estimated. Clinicopathologic features and PET/computed tomography avidity changes were assessed for their potential predictive impact using the log-rank test. RESULTS: From 2011 to 2018, 37 consecutive cases of localized high-risk STS were identified. Twenty-nine patients underwent ifosfamide-based NA-CRT to a median dose of 50 Gy before en bloc resection. At a median follow-up of 40.3 months, estimated 5-year overall survival was 86.1%, disease-free survival 70.2%, distant metastasis-free survival 75.2%, and LC 86.7%. Following NA-CRT, a median reduction of 54.7% was observed in tumor PET avidity; once resected, median tumor necrosis of 60.0% with no viable tumor cells was detected in 13.8% of the cases. Posttreatment resection margins were negative in all patients, with 27.6% having a margin of ≤1 mm. Delays of over 6 weeks following the end of radiation treatment to surgical resection occurred in 20.7% cases and was suggestive of inferior LC (92.8% vs. 68.6%, P=0.025). CONCLUSIONS: This single-institution series of NA-CRT demonstrates favorable disease control. Delay in surgical resection was associated with inferior LC, a finding that deserves further evaluation in a larger cohort. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Excision of Prominent Bony Mass due to Skeletal Fluorosis: A Case Report.

CASE: A 72-year-old man presented for evaluation of bony prominences over extremities. Radiographic imaging demonstrated masses of varying sizes extending from the cortical surfaces without medullary continuity. The patient had a history of Freon inhalation abuse and was diagnosed with skeletal fluorosis due to elevated serum fluoride levels. He underwent an uncomplicated excision of a left fibular mass that was threatening skin breakdown. CONCLUSIONS: This is the first reported surgical case of skeletal fluorosis demonstrating continued enlargement of bony prominences throughout the body. Skeletal fluorosis not only causes diffuse mineralization but may also lead to protruding lesions throughout the body.

Diagnosis and management of primary malignant tumors in the upper extremity.

Bone and soft tissue sarcomas of the upper extremity are relatively uncommon. In many cases, they are discovered incidentally during evaluation of traumatic injuries or common ailments such as rotator cuff tendonitis or tennis elbow. Thus, it is important for all orthopedic surgeons to understand the differential diagnosis, workup, and treatment for upper extremity lesions. An appreciation of the clinical and radiographic features of primary malignant lesions aids in identifying patients that need referral to an orthopedic oncologist and a multidisciplinary team.

Evaluation and Management of Pediatric Bone Lesions.

Bone abnormalities on pediatric radiographs are not uncommon findings for both the general orthopedist as well as the specialist. Although the majority of lesions encountered are benign, the treating physician should also be aware of more concerning diagnoses. General orthopedists and pediatric orthopedists should exhibit a basic level of comfort with working up and diagnosing these benign lesions. When evaluating the pediatric patient with a bone lesion it is crucial to keep in mind important aspects of the clinical history, physical exam, and radiographic findings. Here we provide a review of important findings for the orthopedic surgeon in each of these areas. Many times diagnoses can be made with these alone. With better understanding of clinical and radiographic features of these lesions the orthopedist should be comfortable knowing which lesions he or she can reasonably treat and which should be referred to an oncologic specialist.

Orthopedic Oncology Caseload Among Orthopedic Surgery Residents.

Despite educational focus regarding orthopedic oncology during residency, assessment of resident orthopedic oncology caseload has not been performed. The purpose of this study was to evaluate orthopedic oncology caseload trends and variation among residents. The Accreditation Council for Graduate Medical Education case log reports for orthopedic surgery residents were reviewed for graduating years 2007 to 2013. Trends in orthopedic oncology cases and variation in the median number of cases performed by residents in the 90th, 50th, and 10th percentiles of caseload were evaluated. The proportion of orthopedic oncology caseload among all cases performed by residents increased significantly (P = 0.005) from 2007 to 2013. Likewise, the mean number of adult (P = 0.002), pediatric (P = 0.003), and total orthopedic oncology cases increased significantly (P = 0.002). On average, residents in the 90th, 50th, and 10th percentiles performed 83, 28, and 3 cases, respectively. The current study demonstrates a significant increase in adult, pediatric, and total orthopedic oncology caseload. There is also evidence of substantial caseload variation among residents. Caseload variation may influence the education and technical proficiency of orthopedic residents.

Synovial Hemangioma Presenting as a Painful Locked Knee A Case Report.

A 39-year-old man presented to orthopaedic care with a painful, fully locked knee. Workup revealed free intraarticular nodules, which were subsequently arthroscopically removed and identified to be synovial hemangioma. To the investigators' knowledge, this is the second reported case of synovial hemangioma presenting as a painful, definitively locked knee. Synovial hemangioma should be considered in the differential diagnosis of knee pain, particularly after more common diagnoses have been ruled out. Efficient and appropriate diagnosis and treatment may result in favorable patient outcomes and avoid long-term disability and dysfunction.

Is Prophylactic Intervention More Cost-effective Than the Treatment of Pathologic Fractures in Metastatic Bone Disease?

BACKGROUND: Metastatic bone disease is a substantial burden to patients and the healthcare system as a whole. Metastatic disease can be painful, is associated with decreased survival, and is emotionally traumatic to patients when they discover their disease has progressed. In the United States, more than 250,000 patients have metastatic bone disease, with an estimated annual cost of USD 12 billion. Prior studies suggest that patients who receive prophylactic fixation for impending pathologic fractures, compared with those treated for realized pathologic fractures, have decreased pain levels, faster postoperative rehabilitation, and less in-hospital morbidity. However, to our knowledge, the relative economic utility of these treatment options has not been examined. QUESTIONS/PURPOSES: We asked: (1) Is there a cost difference between a cohort of patients treated surgically for pathologic fractures compared with a cohort of patients treated prophylactically for impending pathologic lesions? (2) Do these cohorts differ in other ways regarding their utilization of healthcare resources? METHODS: We performed a retrospective study of 40 patients treated our institution. Between 2011 and 2014, we treated 46 patients surgically for metastatic lesions of long bones. Of those, 19 (48%) presented with pathologic fractures; the other 21 patients (53%) underwent surgery for impending fractures. Risk of impending fracture was determined by one surgeon based on appearance of the lesion, subjective symptoms of the patient, cortical involvement, and location of the lesion. At 1 year postoperative, four patients in each group had died. Six patients (13%) were treated for metastatic disease but were excluded from the retrospective data because of a change in medical record system and inability to obtain financial records. Variables of interest included total and direct costs per episode of care, days of hospitalization, discharge disposition, 1-year postoperative mortality, and descriptive demographic data. All costs were expressed as a cost ratio between the two cohorts, and total differences between the groups, as required per medical center regulations. All data were collected by one author and the medical center's financial office. RESULTS: Mean total cost was higher in patients with pathologic fractures (cost unit [CU], 642 ± 519) than those treated prophylactically without fractures (CU, 370 ± 171; mean difference, 272; 95% CI, 19-525; p = 0.036). In USD, this translates to a mean of nearly USD 21,000 less for prophylactic surgery. Mean direct cost was 41% higher (nearly USD 12,000) in patients with a pathologic fracture (CU, 382 ± 300 versus 227 ± 93; mean difference, 155; 95% CI, 9-300; p = 0.038). Mean length of stay was longer in patients with pathologic fractures compared with the group treated prophylactically (8 ± 6 versus 4 ± 3 days; mean difference, 4; 95% CI, 1-7; p = 0.01). CONCLUSIONS: These findings show economic and clinical value of prophylactic stabilization of metastatic lesions when performed for patients with painful lesions compromising the structural integrity of long bones. Patients sustaining a pathologic fracture may represent a more severe, sicker demographic than patients treated for impending pathologic lesions. LEVEL OF EVIDENCE: Level IV, economic and decision analysis.

Identification of Risk Factors for Acute Surgical Site Infections in Musculoskeletal Tumor Patients Using CDC/NHSN Criteria.

BACKGROUND: Acute surgical site infections (SSI) are well-recognized postoperative complications, representing a significant source of patient morbidity and cost to the healthcare system. This study is among the first to use standardized criteria for the diagnosis of acute SSI in orthopaedic oncology. METHODS: The medical records of 165 patients were retrospectively reviewed for the occurrence of superficial or deep SSI as defined by the Center for Disease Control's National Healthcare Safety Network (CDC/NHSN) criteria. Patient, disease, and procedure-specific variables were evaluated as potential risk factors for infection. RESULTS: The overall rate of acute SSI was 10.3%. Univariate analysis demonstrated the significance of malignant pathology (p < 0.001), ASA classification (p = 0.009), operative duration (p < 0.001), intraoperative RBC transfusions (p = 0.03), the performance of an amputation (p = 0.016), and race (p = 0.008) on the incidence of SSI. Prolonged operative duration (p = 0.014) and race (p = 0.005) were found to be independent risk factors with odds ratios of 1.89 (95%, CI: 1.14 to 3.14) and 0.047 (95%, CI: 0.006 to 0.387), respectively. CONCLUSIONS: By using the CDC/NHSN guidelines for the diagnosis of acute SSI, we identified prolonged operative time and non-Caucasian race as independent risk factors for infection in musculoskeletal tumor patients.

Maffucci Syndrome. An Interesting Case and a Review of the Literature.

Maffucci syndrome, a rare sporadic form of enchondromatosis, is characterized by hemangiomas and multiple enchondromas, benign cartilaginous tumors that arise near growth plates. Previous studies demonstrate that individuals diagnosed with Maffucci syndrome have approximately 100% lifetime risk of malignant transformation. Identification of Maffucci syndrome by surgical excision and pathological diagnosis can be life-saving due to its high malignant potential relative to other subtypes of enchondromatosis such as Ollier's disease. We report a case of a 58-year-old man with enchondromatosis who experienced malignant transformation of the enchondroma in his distal femur into a chondrosarcoma. He underwent a right distal femoral replacement without complications. Two years later, new masses were identified in his left hand and excised following progressive growth, pain, and functional limitation. Pathology confirmed these to be hemangiomas, and he was diagnosed with Maffucci syndrome. At last follow-up, patient reported additional nodular tumor growths occurring unilaterally on the left side. For patients with Maffucci syndrome, continual follow-up and careful surveillance of these masses is crucial as these lesions can cause fractures, deformities, pain, and undergo malignant transformation. Our report reviews the literature and outlines the treatment and management plans for patients with this rare and potentially dangerous disorder.

Minimizing Blood Loss in Orthopaedic Surgery The Role of Antifibrinolytics.

Many common orthopaedic procedures are associated with a large volume of blood loss. Antifibrinolytics have a well-elucidated mechanism of action and a long history of clinical use. By inhibiting the enzymatic breakdown of fibrin, there has been a demonstrated ability to decrease total blood loss and reduce postoperative transfusion requirements. Despite substantial use in cardiac surgery, antifibrinolytic use in orthopaedic surgery has been limited due to concerns over the potential for venous thromboembolism. A growing body of evidence demonstrates the medications' efficacy and safety in arthroplasty and spine surgery. Due to the risks associated with allogenic blood transfusions and the limitations of alternative blood conservation strategies, antifibrinolytics are a reasonable strategy in blood conservation programs for patients undergoing major orthopaedic procedures.

Large solitary glomus tumor of the wrist involving the radial artery.

Glomus tumors are neuromyoarterial glomus body neoplasms that most commonly occur in the subungual areas of the hand. These tumors typically present as painful solitary lesions with localized tenderness. Extradigital glomus tumors are rare and difficult to diagnose because of their varying symptoms and presentation. Misdiagnosis can result in significant chronic pain, disuse syndromes, and disability over prolonged periods. Timely diagnosis and surgical resection are generally curative with complete resolution of symptoms. Surgeons should be aware of this rare condition and consider it in the differential diagnosis when treating a painful soft-tissue mass of the wrist. We report a case of a large solitary glomus tumor that occurred on the volar-radial aspect of the wrist and involved the radial artery. The patient was successfully treated with complete surgical excision of the tumor. There were no symptoms or recurrence at 3-year follow-up. In the literature, this is the first case of large atypical wrist glomus tumor involving the radial artery to be reported with corresponding magnetic resonance imaging, intraoperative, histology, and immunohistochemistry findings.

Feasibility and efficacy of local radiotherapy with concurrent novel agents in patients with multiple myeloma.

INTRODUCTION: This study evaluated the safety and efficacy of radiotherapy (RT) with concurrent novel agents (NAs), cytotoxic therapy (CTx), or both in the management of osteolytic bone lesions in multiple myeloma (MM). PATIENTS AND METHODS: A total of 39 patients with MM received RT to 64 different bone sites during the 2007-2012 period, with a dose of 8 to 37.5 Gy (mean, 26.8 Gy) delivered in 1 to 15 fractions (median, 10 fractions). Of these patients, 21 also received concurrent NAs or CTx. Pain response, M protein and κ light chain response, and adverse events were evaluated. RESULTS: RT was completed in 35 of 39 patients (89.7%) in this study. Pain relief was observed in 30 of 31 patients (96.7%). Hematologic toxicity (grade 3 or 4 by the Radiation Therapy Oncology Group system) was seen in 43.2% of treated patients, and NA therapy was stopped in 2 patients owing to grade 4 toxicity. RT adverse effects resolved at 4 to 6 weeks posttreatment. Changes in pre- and posttreatment levels of M protein trended toward significance in patients treated with RT + systemic therapy (ST) versus. RT alone (ΔM ProteinRT+ST = 5.6 g/L; ΔM ProteinRT = 0 g/L; P = .089). CONCLUSION: Treating MM with RT concurrently with CTx including NAs was safe and well tolerated in the majority of patients (14 of 16 [87.5%] for those taking NAs and 19 of 21 [90.5%] for all patients). Excellent clinical pain response (> 95%) was also seen in patients regardless if they were treated with RT + ST or RT alone.

"Incidental" bone lesions--when to refer to the tumor specialist.

Incidental bone tumors are, by definition, asymptomatic lesions that are discovered through routine radiographs obtained for other reasons. Generally, these lesions are benign and latent, requiring no further intervention except observation. However, occasionally these radiographs will detect benign aggressive processes or even malignant lesions that do require further treatment and referral to a tumor specialist. Oftentimes, there are characteristic findings on radiographs that are pathognomonic. Knowledge of these findings can simplify the treatment algorithm for a practicing general orthopaedist. This article will describe radiographic characteristics of benign and malignant bone lesions and their typical presentations. It will then focus on the types of bone lesions that are often found incidentally by routine radiography. Specific recommendations, including recommendation for referrals to orthopaedic tumor specialists, will be noted for lesions described. Most malignant lesions will present with pain and a constellation of history and physical exam findings that will signal the patient to seek medical care; although they will be mentioned for the sake of comparison and completeness, they will not be the focus of this review.

Aneurysmal bone cyst.

Aneurysmal bone cysts are rare skeletal tumors that most commonly occur in the first two decades of life. They primarily develop about the knee but may arise in any portion of the axial or appendicular skeleton. Pathogenesis of these tumors remains controversial and may be vascular, traumatic, or genetic. Radiographic features include a dilated, radiolucent lesion typically located within the metaphyseal portion of the bone, with fluid-fluid levels visible on MRI. Histologic features include blood-filled lakes interposed between fibrous stromata. Differential diagnosis includes conditions such as telangiectatic osteosarcoma and giant cell tumor. The mainstay of treatment is curettage and bone graft, with or without adjuvant treatment. Other management options include cryotherapy, sclerotherapy, radionuclide ablation, and en bloc resection. The recurrence rate is low after appropriate treatment; however, more than one procedure may be required to completely eradicate the lesion.

Massive subacromial-subdeltoid bursitis with rice bodies secondary to an orthopedic implant.

Both early and late complications following open reduction and internal fixation of proximal humerus fractures have been reported extensively in the literature. Although orthopedic implants are known to cause irritation and inflammation, to our knowledge, this is the first case report to describe a patient with rice bodies secondary to an orthopedic implant. Although the etiology of rice bodies is unclear, histological studies reveal that they are composed of an inner amorphous core surrounded by collagen and fibrin. The differential diagnosis in this case included synovial chondromatosis, infection, and the formation of a malignant tumor. Additional imaging studies, such as magnetic resonance imaging, and more specific tests were necessary to differentiate the rice bodies due to bursitis versus neoplasm, prior to excision. The patient presented 5 years following open reduction and internal fixation of a displaced proximal humerus fracture, with swelling in the area of the previous surgical site. Examination revealed a large, painless tumor-like mass on the anterior aspect of the shoulder. The patient's chief concern was the unpleasant aesthetic of the mass; no pain was reported. Upon excision of the mass, the patient's full, painless range of motion returned.

The use of radiofrequency ablation in the treatment of musculoskeletal tumors.

Musculoskeletal tumors, both primary neoplasms and metastatic lesions, present a therapeutic challenge for the physician who wishes to provide palliative pain relief using the least invasive approach. The increasing sophistication of imaging modalities such as CT in precisely localizing neoplasm, coupled with the widespread use of radiofrequency ablation (RFA) for treatment of other types of tumor, has generated interest in using RFA to treat musculoskeletal tumors. Primary bone tumors (eg, osteoid osteoma) and metastatic bone tumors have been successfully treated with RFA. Success rates with RFA are equal to those with standard surgical curettage, but RFA has the advantage of decreased surgical morbidity. The procedure is relatively safe, is well-tolerated by the patient, and typically can be performed on an outpatient basis. The most common serious complication reported is localized skin necrosis, which occurs rarely. RFA appears to be a viable minimally invasive approach for palliative treatment of selected bone tumors.

Megaprosthesis versus Condyle-sparing intercalary allograft: distal femoral sarcoma.

UNLABELLED: Although functionally appealing in preserving the native knee, the condyle-sparing intercalary allograft of the distal femur may be associated with a higher risk of tumor recurrence and endoprosthetic replacement for malignant distal femoral bone tumors. We therefore compared the risk of local tumor recurrence between patients in these two types of reconstruction groups. We retrospectively reviewed 85 patients (mean age, 22 years; range, 4-82 years), 38 (45%) of whom had a condyle-sparing allograft and 47 (55%) of whom had endoprostheses. The minimum followup for both groups was 2 years (mean, 7 years; range, 2-19 years). Local recurrences occurred in 11% (five of 47) of the patients having implants versus 18% (seven of 38) of the patients having allografts. Using time to local recurrence as an end point, the Kaplan-Meier survivorship of the implant group was similar to that of the condyle-sparing allograft group at 2, 5, and 10 years (93% versus 87% at 2 years, 87% versus 81% at 5 years, and 87% versus 81% at 10 years, respectively). The condyle-sparing allograft procedure offers the potential advantage of retaining the native knee in a young patient population while incurring no greater risk of local recurrence as those offered the endoprosthetic procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells.

Human myxoid liposarcoma contains a characteristic t(12;16) chromosomal translocation that results in fusion of the N-terminal domain of the translocated in liposarcoma (TLS) protein to the C/EBP homologous protein (CHOP). TLS possesses structural motifs that suggest it may participate in RNA processing. We demonstrate that in human myxoid liposarcoma cells, wild-type TLS binds to RNA polymerase II (Pol II) via its N-terminal domain and to the transcription and translation factor Y-box binding protein-1 (YB-1) through its C-terminal domain. The liposarcoma fusion protein TLS/CHOP retains the ability to bind RNA Pol II but lacks the ability to recruit YB-1 due to replacement of the C-terminal domain of TLS by CHOP. In an in vivo splicing assay, YB-1 promotes splicing of adenovirus EIA pre-mRNA predominantly to the 13S isoform. The oncogenic TLS/CHOP fusion protein inhibits this splicing function of YB-1 in a dominant negative manner. When considered in conjunction with studies on other sarcoma fusion proteins, these data suggest that aberrant RNA splicing may be a common feature of human sarcomas.