What's Wrong With the Bone? An Overview of Metabolic and Neoplastic Bone Conditions.

The evaluation of any orthopaedic condition often begins with obtaining plain radiographs. Fortuitously, plain radiographs provide surgeons with direct information on the biologic activity and, therefore, the aggressiveness of any bone lesion. More advanced imaging modalities may fail to elucidate the problem and may even obscure the diagnosis. The accurate interpretation of the aggressiveness of a bone lesion on plain radiographs is the first step in establishing a differential diagnosis for any bone lesion and, often, may result in a correct diagnosis without the need for additional imaging studies. A thorough understanding of the radiographic classification of bone lesions will allow surgeons to accurately diagnose and manage metabolic bone disease, benign bone lesions, and malignant bone lesions.

Angiosarcoma of the humerus presenting with fluid-fluid levels on MRI: a unique imaging presentation.

Fluid-fluid levels are a known feature of a number of osseous lesions, but have never before been described in primary osseous angiosarcoma, which is itself a rare malignancy. We report a case of humeral angiosarcoma presenting with fluid-fluid levels. Recognizing this entity as a possible etiology for fluid-fluid levels could help radiologists to avoid potential confusion in the differential diagnosis on imaging.

2011 Mid-America Orthopaedic Association Dallas B. Phemister Physician in Training Award: Can musculoskeletal tumors be diagnosed with ultrasound fusion-guided biopsy?

BACKGROUND: Percutaneous biopsy for musculoskeletal tumors commonly relies on imaging adjuncts including ultrasound (US), CT, or MRI. These modalities however have disadvantages (US) or are cumbersome, not universally available, and costly (CT and MRI). US fusion is a novel technique that fuses previously obtained CT or MRI data with real-time US, which allows biopsies to be performed in an US suite. It has proven useful in various body systems but musculoskeletal applications remain scarce. Our goal is to evaluate the fusion technology and determine its ability to diagnose musculoskeletal tumors. QUESTIONS/PURPOSES: We determined whether biopsies performed via US fusion compared with CT guidance provide equivalent diagnostic yield and accuracy and allow quicker biopsy scheduling and procedure times. METHODS: Forty-seven patients were assigned to undergo either US fusion (with MR, n = 16 or CT, n = 15) or CT-guided biopsies (n = 16). We evaluated adequacy of the histologic specimen (diagnostic yield) and correlation with surgical pathology (diagnostic accuracy). We determined scheduling times and lengths of the biopsy. RESULTS: US fusion and CT-guided biopsy groups had comparable diagnostic yields (CT = 94%; US/MRI = 94%; US/CT = 93%) and accuracy (CT = 83%; US/MRI = 90%; US/CT = 100%). US fusion biopsies were faster to schedule and perform. All procedures were safe with minimal complications. CONCLUSIONS: US fusion provides a high diagnostic yield and accuracy comparable to CT-guided biopsy while performed in the convenience of an US suite. This may have resulted in the observed faster scheduling and biopsy times. LEVEL OF EVIDENCE: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Tumors for the general orthopedist: how to save your patients and practice.

It is likely that most orthopaedic surgeons will see a patient with a benign or malignant musculoskeletal tumor sometime during their career. However, because of the rarity of these entities, many surgeons may benefit from a review of how to evaluate a patient with a bone lesion or soft-tissue mass. A logical approach is necessary in evaluating imaging studies as well as in the workup of children and adults with a possible tumor. It is important to have a good working relationship with a musculoskeletal radiologist to assist in interpreting the images. If the treatment algorithms lead to a conclusive diagnosis of a benign bone tumor, benign soft-tissue mass, or metastatic bone disease, the orthopaedic surgeon may choose to definitively treat the patient. If the workup indicates an indeterminate lesion, it may be prudent to discuss the situation with an orthopaedic oncologist or transfer the care of the patient to a physician with more specialized knowledge. A careful, logical workup is needed prior to surgery to limit risks to the patient and optimize the chances for a favorable outcome.

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma With Features Mimicking Spindle Cell Lipoma.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and spindle cell lipoma are lipomatous tumors with distinct clinical, molecular, and prognostic features. Although histological and immunophenotypic features can overlap between ALT/WDL and spindle cell lipoma, the oncogenesis and clinical behavior are markedly different. In borderline cases, molecular analysis for MDM2 or CDK4 amplification can aid in distinguishing ALT/WDL from spindle cell lipoma. Although dedifferentiated liposarcoma has been reported to harbor both MDM2 amplification and loss of the RB1 region, we are not aware of a reported RB1 loss in well-differentiated ALT/WDL. In this article, we present a 69-year-old woman with a lipomatous tumor in the gluteal region that histologically, immunohistochemically, and molecularly mimicked spindle cell lipoma (with positive immunohistochemical staining for CD34 and loss of the RB1 gene region), yet harbored amplification of MDM2 and CDK4 confirmed by fluorescence in situ hybridization, supporting classification as ALT/WDL. This case strengthens the argument that in atypical clinical contexts, molecular studies for MDM2/CDK4 should be considered in tumors resembling spindle cell lipoma.

Association of Preoperative Patient Frailty and Operative Stress With Postoperative Mortality.

Importance: Patients with frailty have higher risk for postoperative mortality and complications; however, most research has focused on small groups of high-risk procedures. The associations among frailty, operative stress, and mortality are poorly understood. Objective: To assess the association between frailty and mortality at varying levels of operative stress as measured by the Operative Stress Score, a novel measure created for this study. Design, Setting, and Participants: This retrospective cohort study included veterans in the Veterans Administration Surgical Quality Improvement Program from April 1, 2010, through March 31, 2014, who underwent a noncardiac surgical procedure at Veterans Health Administration Hospitals and had information available on vital status (whether the patient was alive or deceased) at 1 year postoperatively. A Delphi consensus method was used to stratify surgical procedures into 5 categories of physiologic stress. Exposures: Frailty as measured by the Risk Analysis Index and operative stress as measured by the Operative Stress Score. Main Outcomes and Measures: Postoperative mortality at 30, 90, and 180 days. Results: Of 432 828 unique patients (401 453 males [92.8%]; mean (SD) age, 61.0 [12.9] years), 36 579 (8.5%) were frail and 9113 (2.1%) were very frail. The 30-day mortality rate among patients who were frail and underwent the lowest-stress surgical procedures (eg, cystoscopy) was 1.55% (95% CI, 1.20%-1.97%) and among patients with frailty who underwent the moderate-stress surgical procedures (eg, laparoscopic cholecystectomy) was 5.13% (95% CI, 4.79%-5.48%); these rates exceeded the 1% mortality rate often used to define high-risk surgery. Among patients who were very frail, 30-day mortality rates were higher after the lowest-stress surgical procedures (10.34%; 95% CI, 7.73%-13.48%) and after the moderate-stress surgical procedures (18.74%; 95% CI, 17.72%-19.80%). For patients who were frail and very frail, mortality continued to increase at 90 and 180 days, reaching 43.00% (95% CI, 41.69%-44.32%) for very frail patients at 180 days after moderate-stress surgical procedures. Conclusions and Relevance: We developed a novel operative stress score to quantify physiologic stress for surgical procedures. Patients who were frail and very frail had high rates of postoperative mortality across all levels of the Operative Stress Score. These findings suggest that frailty screening should be applied universally because low- and moderate-stress procedures may be high risk among patients who are frail.

VEGF blockade decelerates the growth of a murine experimental osteosarcoma.

Retrovirus-mediated sFlt-1 gene modification was performed to examine the influence of VEGF in controlling the growth of an experimental osteosarcoma in mice. Human osteosarcoma G-292 cells were in vitro infected with retroviral vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal tibiae of immune deficient SCID mice to establish experimental orthotopic osteosarcoma. Daily observation and biweekly microCT were performed to monitor tumor development and progression till sacrifice at 8 weeks after tumor cell inoculation for histological and molecular analyses. Successful transgene expression was confirmed in the culture media of sFlt-1 transduced G-292 cells using ELISA, and with positive X-gal staining of the LacZ transduced cells. Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell inoculation, with clear detection on microCT images starting 2 weeks after inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292 cells were distinctively smaller in size when compared to the ones from wide-type G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics including severe cellular pleomorphism, bone erosions, and neo-vascularization. Real-time polymerase chain reaction indicated significantly higher sFlt-1 expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ-treated groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along with the expression of VEGF in the primary tumor tissue. Overall, data suggest that retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.

Giant Cell Tumor of Bone Presenting as Left Posteromedial Chest Wall Tumor.

Giant cell tumor is a relatively uncommon bone tumor rarely originating from the chest wall. Given its proximity to vital structures in the thoracic cavity, treatment options may be challenging. We report the case of a patient with a giant cell tumor of the posterolateral chest wall with invasion of the thoracic spine treated with neoadjuvant denosumab, followed by surgical resection.

Sacroiliac stabilization for sacral metastasis: A case series.

BACKGROUND: The sacrum is a rare location for spinal metastasis. These lesions are typically large and destructive by the time of diagnosis, making treatment difficult. When indicated, surgical stabilization offers pain relief and preserves independence in patients with impending and acute pathological sacral fractures. CASE DESCRIPTION: Three consecutive patients presented with sacral metastases. After either failing radiation therapy or presenting with acute fracture and instability, the patients underwent intralesional excision, bilateral L4 to ilium fusion with instrumentation, and sacroiliac (SI) screw fixation. Pain improved after surgery, and there were no wound healing complications. Two patients could continue walking without any assistive device, while one patient required a walker. CONCLUSION: Stabilization with combined modified Galveston fixation and SI screw fixation relieves pain and allows maintenance of independence in patients with sacral metastasis.

Eponymous Instruments in Orthopaedic Surgery.

Every day surgeons call for instruments devised by surgeon trailblazers. This article aims to give an account of commonly used eponymous instruments in orthopaedic surgery, focusing on the original intent of their designers in order to inform how we use them today. We searched PubMed, the archives of longstanding medical journals, Google, the Internet Archive, and the HathiTrust Digital Library for information regarding the inventors and the developments of 7 instruments: the Steinmann pin, Bovie electrocautery, Metzenbaum scissors, Freer elevator, Cobb periosteal elevator, Kocher clamp, and Verbrugge bone holding forceps. A combination of ingenuity, necessity, circumstance and collaboration produced the inventions of the surgical tools numbered in our review. In some cases, surgical instruments were improvements of already existing technologies. The indications and applications of the orthopaedic devices have changed little. Meanwhile, instruments originally developed for other specialties have been adapted for our use. Although some argue for a transition from eponymous to descriptive terms in medicine, there is value in recognizing those who revolutionized surgical techniques and instrumentation. Through history, we have an opportunity to be inspired and to better understand our tools.

Superficial CD34-positive fibroblastic tumor: Cytologic features, tissue correlation, ancillary studies, and differential diagnosis of a recently described soft tissue neoplasm.

Superficial CD34-positive fibroblastic tumor is a low-grade mesenchymal neoplasm of superficial soft tissues characterized by fascicles of spindle to epithelioid cells displaying nuclear pleomorphism and strong diffuse CD34 immunoreactivity. The intraoperative imprint cytology preparations (ICP) of a superficial CD34-positive fibroblastic tumor from a 50-year-old female are described. To the best of our knowledge, there is no report of the cytologic findings of superficial CD34-positive fibroblastic tumor in the English medical literature. The ICP, differential diagnosis, tissue correlation, and ancillary studies of this fascinating entity are discussed. Diagn. Cytopathol. 2016;44:926-930. © 2016 Wiley Periodicals, Inc.

Ewing Sarcoma in the Fifth Metacarpal of an Adult Woman: A Case Report.

CASE: Atypical presentations of Ewing sarcoma (ES) can lead to misdiagnosis and delays in treatment. We present a rare case of ES in the hand of an adult woman who underwent multiple interventions prior to referral to our institution. At 22 months after definitive treatment, the patient remained pleased with the result and had no evidence of recurrence. CONCLUSION: To our knowledge, ES of the hand in an adult woman has not yet been reported in the literature, and a lack of recognition of this condition might be secondary to the absence of features traditionally associated with malignant bone neoplasms. A broader differential diagnosis after intervention failures offers the opportunity for diagnosis and appropriate treatment.

Long-term outcome of combined modality therapy in retroperitoneal and deep-trunk soft-tissue sarcoma: analysis of prognostic factors.

PURPOSE: To evaluate the long-term outcome of surgery and postoperative radiotherapy (RT) in retroperitoneal and deep-trunk soft-tissue sarcoma, and to identify the prognostic factors for local control, disease-free survival, and overall survival. METHODS AND MATERIALS: Between January 1980 and December 1998, 60 patients with nonmetastatic retroperitoneal and deep-trunk soft-tissue sarcoma were treated at Wayne State University using combined surgery and RT. The location was retroperitoneal in 38 patients (63%) and deep trunk in 22 (27%). Forty-six patients (76%) were treated for primary disease and 14 (24%) for recurrent disease. The resection margins were negative in 24 patients (40%), close in 3 (5%), and positive in 33 (55%; 18 microscopic and 15 macroscopic). The median tumor size was 8.6 cm (range 2-55). External beam RT (EBRT; median dose 5220 cGy) was given to 44 patients (73%) and combined EBRT (median dose 4200 cGy) and brachytherapy (median dose 1600 cGy) to 16 patients (27%). Univariate and multivariate Cox regression analyses were conducted to identify the possible associations between patient age, race, gender, tumor site, histologic features, grade, size, stage, surgical margin, RT dose, modality (EBRT vs. EBRT plus brachytherapy), and presentation (primary vs. recurrent) and disease control. RESULTS: The actuarial 5- and 10-year disease-free survival rate was 53% and 44%, respectively. Disease-free survival was significantly associated with female gender on univariate analysis (67% for female patients and 37% for male patients at 5 years, p = 0.05). On multivariate analysis, both gender and surgical margin had borderline significance (p = 0.06). The actuarial local control rate was 71% and 54% at 5 and 10 years, respectively. The median time to local relapse was 10.2 months, with 75% of all failures occurring within 29 months. The surgical margin status was significantly associated with local control (78% for patients with negative or close margins vs. 52% for patients with positive margins at 5 years, p = 0.04). Gender was borderline significant (85% for female patients vs. 54% for male patients at 5 years, p = 0.06). On multivariate analysis, only surgical margin status remained significant (p = 0.032). The distant metastasis-free survival rate at 5 and 10 years was 58% and 54%, respectively. The median time to distant metastases was 15.6 months. The lungs were the most common site of metastases. The only significant factor associated with distant metastasis-free survival was local control (73% for patients with locally controlled tumors vs. 19% for patients with local recurrence at 5 years, p = 0.0013). The actuarial 5- and 10-year overall survival rate was 56% and 47%, respectively. Gender (74% for female patients vs. 37% for male patients at 5 years), surgical margin status (66% for patients with negative or close margins vs. 48% for patients with positive margins at 5 years), and local control (64% for patients with locally controlled tumors vs. 21% for patients with uncontrolled primary tumors at 5 years) were significant predictors on both univariate and multivariate analyses (p <0.05). CONCLUSION: The results of this study demonstrate the paramount importance of local control and complete surgical resection in the management of soft-tissue sarcoma of the retroperitoneum and deep trunk.

Osteosarcoma as a second malignant neoplasm.

PURPOSE: The aim of this study is to compare primary and secondary osteosarcomas using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. METHODS: Osteosarcoma cases were identified in the SEER Cancer Incidence Public-Use Database, 1973-96 (1,511 primary and 133 secondary osteosarcomas). Secondary osteosarcomas were further classified as occurring within or outside the previously irradiated field. Comparisons among groups were performed by nominal logistic regression. Survival analyses were performed using Kaplan-Meir and proportional hazards regression. RESULTS: Secondary osteosarcomas were more likely to have a non-extremity primary site and an older age at diagnosis (>40 years) (<0.0001 for both). Secondary osteosarcoma cases continued to be more likely to have a non-extremity site when excluding those occurring within the radiation field. Five-year overall survival was 50% lower for secondary osteosarcomas for both extremity and non-extremity sites. Primary malignancies associated with secondary osteosarcomas included 14 lymphomas/leukemias, six sarcomas, 54 carcinomas, and seven other cancers. Secondary osteosarcomas occurring within a field of radiation were more likely to occur at a younger age, have a malignancy with a primary morphology other than carcinoma, a non-limb site, and a longer duration between their primary malignant neoplasms and the development of osteosarcoma. No difference in the overall survival was noted between secondary osteosarcomas occurring within an irradiated field and those that did not. CONCLUSIONS: Secondary osteosarcomas are associated with carcinomas especially in the elderly. Although a 50% decreased 5-year survival was observed for secondary osteosarcomas in this study, this might not reflect the current outcomes with more aggressive therapy.

c-Kit expression in desmoid fibromatosis. Comparative immunohistochemical evaluation of two commercial antibodies.

To determine the frequency of c-Kit staining in desmoids and optimize an assay for clinical use, we stained 19 desmoids from various sites at various dilutions with 2 commonly used rabbit polyclonal, anti-c-Kit antibodies (A4502, DAKO, Carpinteria, CA; C-19, Santa Cruz Biotechnology, Santa Cruz, CA), with and without heat-induced epitope retrieval (HIER) in citrate buffer. Approdpriate external and internal control samples were evaluated for each test condition. At dilutions of 1:50 both antibodies stained substantial numbers of desmoids: with/without HIER, A4502, 89%/63%; C-19, 37%/74%. The staining was cytoplasmic without cell membrane accentuation. However, background stromal staining and nonspecific staining of endothelium and smooth and striated muscle were problematic with both antibodies at 1:50. At higher dilutions, C-19 stained no desmoid; however, diminished staining of external and internal control samples made it unreliable. A4502 similarly stained many fewer desmoids at higher dilutions. However, it retained strong staining of both external and internal control samples and showed much less nonspecific staining. Best results were achieved at 1:250 without HIER; only weak focal staining was present in 1 desmoid. With a simple immunohistochemical method optimized for clinical use, desmoid can be regarded as a c-Kit-negative tumor.

The supporting effects of high luminous conditions on grade 3 oral reading fluency scores.

The universality of the impact of daylight is a common thread that defines humanity. Day light affects us in a variety of ways -visually, psychologically and biologically. Artificial lighting research has explored ways in which artificial lighting may substitute for daylight and enhance human health and wellbeing. Recently, a study by Mott et al. 2011 found that the usage of high intensity, yet glare free lighting, (referred to as Focus light setting) during reading instruction increased grade 3 students' oral reading fluency (ORF) scores, a key index of reading comprehension. The current study further explored the effect of Focus lighting during literacy instruction with at-risk grade 3 students (n = 172). Over the course of an academic year, the Focus lighting students increased their ORF scores at a greater rate than did the Normal lighting students. These findings, in combination with earlier lighting research, suggest that artificial lighting plays a key role in helping to create an effective learning environment to ensure children reach their full potential. More systematic research, however, is needed to understand the mechanisms by which artificial lighting may contribute to the learning environment: visually, biologically and/or psychologically.

Virtual morality: emotion and action in a simulated three-dimensional "trolley problem".

Experimentally investigating the relationship between moral judgment and action is difficult when the action of interest entails harming others. We adopt a new approach to this problem by placing subjects in an immersive, virtual reality environment that simulates the classic "trolley problem." In this moral dilemma, the majority of research participants behaved as "moral utilitarians," either (a) acting to cause the death of one individual in order to save the lives of five others, or (b) abstaining from action, when that action would have caused five deaths versus one. Confirming the emotional distinction between moral actions and omissions, autonomic arousal was greater when the utilitarian outcome required action, and increased arousal was associated with a decreased likelihood of utilitarian-biased behavior. This pattern of results held across individuals of different gender, age, and race.

Device preview: Touch-user interface books for overcoming reading difficulty.

PURPOSE: To provide a rationale for the newly developed paper-to-digital book product, touch-user-interface (TUI) technology for improving reading comprehension for students with disabilities and developmental constraints. METHOD: TUI technology, enabling students to touch portions of the pages to actualise corresponding digital files, was theoretically and practically analysed by the author, a content-area expert in (a) reading fluency and comprehension and (b) learning disabilities, for judgment of product utility. Product function was juxtaposed with current reading research depicting learner challenges to fluency and comprehension. RESULTS: TUI technology provides design solutions in-line with meeting student challenges with reading difficulty, namely that traditional paper book pages with 'too much' text block reading comprehension due to low fluency (reading rate is too slow for the brain to make sense of text causing a 'bottleneck' effect) inhibiting understanding. It is proposed that with a TUI book, with media-rich paper, less text can be used and informational equivalence achieved with the digital material activated via touch points on paper pages tethered to a computer. The audio, video and graphics meaning-based symbols systems can replace some text. CONCLUSIONS: TUI technology function needs to be evaluated in applied research in classroom settings across exceptionality and development.

Venous hemangioma presenting as a superior sulcus tumor.

Non-small cell pulmonary carcinomas represent the majority of tumors located in the superior sulcus. However, only 5% of all non-small cell pulmonary carcinomas present in the superior sulcus. Other causes of superior sulcus tumors include metastatic tumors, hematologic malignancies, infectious causes, and amyloid nodules, as well as other lesions. We report a case in which a venous hemangioma presented as a superior sulcus tumor.