Current Biopsy Methods for Primary Musculoskeletal Lymphoma: A Retrospective Multicenter Review.

Primary musculoskeletal lymphoma often requires multiple biopsies for tissue confirmation. This challenge is understood by specialists but has not been specifically quantified. One-hundred-eighteen biopsies performed in 100 cases of primary musculoskeletal lymphoma was performed. Demographics, tumor location and the method and performer of biopsy were recorded. Pearson chi-square and analysis of variance (ANOVA) statistics were used to compare rates of diagnostic yield, time to diagnosis and the presence of crush artifact based on method of biopsy, imaging, performer and tumor location. Diagnostic yield of initial biopsy is 82%. Open biopsy is associated with a higher yield compared to percutaneous techniques (p = 0.005). Biopsies performed by the treating surgeon had a higher yield compared to other practitioners (p = 0.035). Musculoskeletal lymphomas are a greater diagnostic challenge compared to other lesions. A higher index of suspicion and more aggressive sampling procedure may be necessary to establish this diagnosis. (Journal of Surgical Orthopaedic Advances 29(3):149-153, 2020).

Evaluating the Role of Interdigitated Neoadjuvant Chemotherapy and Radiation in the Management of High-Grade Soft-Tissue Sarcoma: The Johns Hopkins Experience.

OBJECTIVES: High-grade soft-tissue sarcoma (STS) has a poor prognosis. The goal of this study was to review treatment outcomes of patients with high-grade STS treated with interdigitated neoadjuvant chemotherapy (CT) and radiation at our institution. MATERIALS AND METHODS: Patients with high-grade STS (1997 to 2010) were planned for treatment with 3 cycles of neoadjuvant CT, interdigitated preoperative radiation therapy (44 Gy administered in split courses with a potential 16 Gy postoperative boost), and 3 cycles of postoperative CT. Cancer control outcomes at 3 years were analyzed. RESULTS: Sixteen patients with high-grade STS were evaluated. Median age was 53 years, the median longest tumor diameter was 14.6 cm, and median follow-up was 33 months. All 16 patients received 2 or 3 cycles of neoadjuvant CT and all patients completed neoadjuvant RT. The estimated 3-year rate for local control was 100%, disease-free survival 62.5%, and overall survival 73.4%. CONCLUSIONS: Patients with high-grade STS treated with interdigitated neoadjuvant CT and radiation before surgical resection had excellent rates of local control, along with disease-free survival and overall survival similar to previously published reports. This combined-modality approach continues to have a role in the treatment of patients with high-grade STS.

Patient Anxiety, Pain, and Satisfaction With Image-Guided Needle Biopsy.

Image-guided percutaneous needle biopsy has become the preferred diagnostic modality for bone and soft tissue tumors. However, to the authors' knowledge, the levels of patient anxiety, pain, and satisfaction before and after the procedure have not been studied. Sixty-five patients undergoing image-guided needle biopsy of a possible bone or soft tissue tumor were prospectively surveyed to quantify preprocedure and postprocedure levels of anxiety and pain and to determine demographic and clinical correlates of anxiety, pain, and satisfaction. Anxiety was measured with the Spielberger State-Trait Anxiety Inventory, pain was measured with a visual analog scale, and satisfaction was measured by patient willingness to repeat the procedure if necessary. Statistical analysis was performed with Student's t test, Fisher's exact test, and linear regression analysis. Compared with preprocedure values, trait anxiety (defined as the underlying level of anxiety, P<.0011), state anxiety (defined as the current level of situational anxiety, P<.001), and pain (P<.05) decreased significantly postprocedure. The relationship between changes in pain and state anxiety was significant (r=0.31, P=.014), whereas no relationship was seen between changes in pain and trait anxiety (r=0.13, P=.28). Patients who were somewhat satisfied with the procedure reported higher levels of postprocedure pain than those who were completely satisfied (5.24±2.19 cm vs 1.70±2.08 cm, respectively; P<.001). In other words, lower levels of experienced pain correlated with patient satisfaction. Older age was inversely correlated with postprocedure pain (r=0.41, P=.001), and there was a trend toward increasing dissatisfaction among younger patients.

Concomitant upper extremity soft tissue sarcoma limb-sparing resection and functional reconstruction: assessment of outcomes and costs of surgery.

BACKGROUND: The purpose of this study is to investigate functional outcomes and cost impacts of immediate functional reconstruction performed in conjunction with limb-sparing resection of upper extremity soft tissue sarcomas. METHODS: Patients undergoing simultaneous limb-sparing upper extremity soft tissue sarcoma resection and functional reconstruction between December 1998 and March 2004 were retrospectively identified, their medical records reviewed, and costs of surgery analyzed. Functional outcomes and patient satisfaction were assessed via patient surveys and the Toronto Extremity Salvage Score (TESS). RESULTS: Thirteen patients met the inclusion criteria. Average follow-up was 43.3 months. Reconstructions included rotational innervated muscle flaps (n = 6), free innervated myocutaneous flaps (n = 1), and tendon transfers or grafts (n = 6). Overall survival was 85 % (n = 11) and disease-free survival was 77 % (n = 10). Average total cost of surgery was $26,655. Patients undergoing reconstruction for hand and forearm sarcomas had significantly higher total costs of surgery than those undergoing reconstruction for elbow and upper arm sarcomas. Survey response rate was 91 % (n = 10). Average TESS score was 76. Of the patients who worked preoperatively, 88 % returned to work postoperatively, and all patients who returned to work currently use their affected limb at work. CONCLUSIONS: Patients undergoing immediate functional reconstruction for upper extremity soft tissue sarcoma resection achieved very good to excellent functional outcomes with quick recovery times and a high return-to-work rate following immediate functional reconstruction, thereby minimizing surgical cost impacts. Immediate functional reconstruction in the same surgical setting is thus a viable strategy following upper extremity soft tissue sarcoma resection.

CASE REPORT Rotational Vascularized Tibiaplasty After Oncologic Resection and Major Wound Healing Problems: A Novel Technique.

OBJECTIVE: To describe a novel method to reconstruct, with a vascularized rotational tibiaplasty, a complex femoral defect in an adolescent. METHODS: After a femoral osteosarcoma resection, allograft reconstruction, and chemotherapy, an 11-year-old girl developed recurrent thigh wound infections and femoral allograft osteomyelitis despite multiple operative interventions. At the age of 13, she presented to our center with a complex right thigh wound and an unstable lower extremity secondary to a segmental femoral loss. To reestablish thigh stability and function and to avoid amputation at the hip, the authors performed a rotational vascularized tibiaplasty. The tibia was rotated 180° with the pivot at the knee. The distal tibia was internally stabilized to the residual proximal femur. RESULTS: Ten years later, the patient had a stable thigh, a functional hip, no evidence of infection or sarcoma, and a Toronto Extremity Salvage Score of 92.5 (minimal disability). CONCLUSIONS: In this patient, the tibial rotationplasty provided a vascularized bone strut mimicking the resected femur; saved the hip; obviated an allograft bone; and created a functional, biologic, stable, and durable thigh that allowed full weight bearing on a prosthesis, with a low physical disability level. We conclude that, for patients with complex femoral defects, a vascularized rotational tibiaplasty should be considered a feasible option before amputation.

Bone cancer.

Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.

Inhibition of TGF-ß signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis.

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor ß1 (TGF-ß1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-ß1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-ß1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-ß1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-ß activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-ß type II receptor (TßRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-ß1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.

A systematic approach to magnetic resonance imaging evaluation of epiphyseal lesions.

Magnetic Resonance Imaging (MRI) is the preferred modality of choice to image epiphyseal lesions. It provides excellent soft tissue resolution and extent of disease. A wide spectrum of tumor and tumor like lesions can involve the epiphysis. Early and accurate diagnosis as well as appropriate management of epiphyseal lesions is critical as these conditions may lead to disabling complications such as, limb length discrepancy, angular or joint surface deformities and secondary osteoarthritis. In this article, we discuss the role of conventional sequences, such as T1W, fluid sensitive T2W and intravenous (IV) Gadolinium enhanced sequences as well as the additional value of problem solving MRI sequences such as, chemical shift and diffusion weighted imaging. Based on the imaging findings on various MRI sequences and lesion characteristics, a systematic approach directed to the diagnoses of epiphyseal lesions is presented and discussed. MRI features of clinically and biopsy proven examples of the epiphyseal lesions, such as osteomyelitis, intra-osseous abscess, infiltrative malignancy, metastases, transient osteoporosis, subchondral insufficiency fracture, avascular necrosis, osteochondral fracture, osteochondritis dissecans, eosinophilic granuloma and geode are demonstrated. Using this systematic approach, the reader will be able to better characterize epiphyseal lesions with a potential to positively affect patient management.

Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells.

Insulin-like growth factor 1 (IGF-1), the most abundant growth factor in the bone matrix, maintains bone mass in adulthood. We now report that IGF-1 released from the bone matrix during bone remodeling stimulates osteoblastic differentiation of recruited mesenchymal stem cells (MSCs) by activation of mammalian target of rapamycin (mTOR), thus maintaining proper bone microarchitecture and mass. Mice with knockout of the IGF-1 receptor (Igf1r) in their pre-osteoblastic cells showed lower bone mass and mineral deposition rates than wild-type mice. Further, MSCs from Igf1rflox/flox mice with Igf1r deleted by a Cre adenovirus in vitro, although recruited to the bone surface after implantation, were unable to differentiate into osteoblasts. We also found that the concentrations of IGF-1 in the bone matrix and marrow of aged rats were lower than in those of young rats and directly correlated with the age-related decrease in bone mass. Likewise, in age-related osteoporosis in humans, we found that bone marrow IGF-1 concentrations were 40% lower in individuals with osteoporosis than in individuals without osteoporosis. Notably, injection of IGF-1 plus IGF binding protein 3 (IGFBP3), but not injection of IGF-1 alone, increased the concentration of IGF-1 in the bone matrix and stimulated new bone formation in aged rats. Together, these results provide mechanistic insight into how IGF-1 maintains adult bone mass, while also providing a further rationale for its therapeutic targeting to treat age-related osteoporosis.

Review of the current literature as a preparatory tool for the trauma content of the Orthopaedic in-Training Examination.

Currently, the only standardized evaluation of trauma knowledge throughout orthopedic training is found in the Orthopaedic In-Training Examination, which is administered annually to all residents by the American Academy of Orthopaedic Surgeons. Our goals were to assess the Orthopaedic In-Training Examination to (1) determine the content of the trauma questions, (2) identify the content of the 3 most frequently referenced journals on the answer keys, and (3) evaluate the correlation between those contents.We reviewed the trauma-related Orthopaedic In-Training Examination questions and answer keys for 2002 through 2007. Content for test questions and cited literature was assessed with the same criteria: (1) category type, (2) anatomic location, (3) orthopedic focus, and (4) treatment type. For each of the 3 most frequently referenced journals, we weighted content by dividing the number of times it was referenced by the number of its trauma-related articles. We then compared the journal data individually and collectively to the data from the Orthopaedic In-Training Examination trauma questions. A chi-square analysis with Yates correction was used to determine differences. Questions and literature were similar in the most frequently addressed items in each of the 4 areas: category type (taxonomy 3, treatment), 52.4% and 60.7%, respectively; anatomic location (femur), 23.3% and 27.7%, respectively; orthopedic focus (fracture), 51.0% and 56.5%, respectively; and treatment type (multiple/nonspecific), 39.0% and 35.4%, respectively.The content correlation found between the questions and literature supports the idea that reviewing current literature may help prepare for the trauma content on the Orthopaedic In-Training Examination.

Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells.

Radiation therapy can result in bone injury with the development of fractures and often can lead to delayed and nonunion of bone. There is no prevention or treatment for irradiation-induced bone injury. We irradiated the distal half of the mouse left femur to study the mechanism of irradiation-induced bone injury and found that no mesenchymal stem cells (MSCs) were detected in irradiated distal femora or nonirradiated proximal femora. The MSCs in the circulation doubled at 1 week and increased fourfold after 4 wk of irradiation. The number of MSCs in the proximal femur quickly recovered, but no recovery was observed in the distal femur. The levels of free radicals were increased threefold at 1 wk and remained at this high level for 4 wk in distal femora, whereas the levels were increased at 1 wk and returned to the basal level at 4 wk in nonirradiated proximal femur. Free radicals diffuse ipsilaterally to the proximal femur through bone medullary canal. The blood vessels in the distal femora were destroyed in angiographic images, but not in the proximal femora. The osteoclasts and osteoblasts were decreased in the distal femora after irradiation, but no changes were observed in the proximal femora. The total bone volumes were not affected in proximal and distal femora. Our data indicate that irradiation produces free radicals that adversely affect the survival of MSCs in both distal and proximal femora. Irradiation injury to the vasculatures and the microenvironment affect the niches for stem cells during the recovery period.

Inhibition of Sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling.

The anabolic effects of parathyroid hormone (PTH) on bone formation are impaired by concurrent use of antiresorptive drugs. We found that the release of active transforming growth factor (TGF)-ß1 during osteoclastic bone resorption is inhibited by alendronate. We showed that mouse Sca-1-positive (Sca-1(+)) bone marrow stromal cells are a skeletal stem cell subset, which are recruited to bone remodeling sites by active TGF-ß1 in response to bone resorption. Alendronate inhibits the release of active TGF-ß1 and the recruitment of Sca-1(+) skeletal stem cells for the bone formation. The observation was validated in a Tgfb1(-/-) mouse model, in which the anabolic effects of PTH on bone formation are diminished. The PTH-stimulated recruitment of injected mouse Sca-1(+) cells to the resorptive sites was inhibited by alendronate. Thus, inhibition of active TGF-ß1 release by alendronate reduces the recruitment of Sca-1(+) skeletal stem cells and impairs the anabolic action of PTH in bone.

Educational resources for the Orthopedic In-Training Examination.

OBJECTIVE: Various educational tools are available for the Orthopedic In-Training Examination (OITE). However, many residents are unsure of which resources are the most useful. This study assessed what educational resources residents consider to be most useful and how the top performers prepare for the examination. METHODS: A web-based survey was distributed to orthopedic residency programs. Residents indicated their program type, year in residency, and most recent OITE score. They also rated (0-4 points) the value of various educational resources. An chi(2) analysis identified resources that were used more frequently by residents who scored in the top 20%. We compared the useful educational resources identified by the entire group, as well as by the top 20% of residents, with what has been the most commonly cited recommended references for the OITE during a 5-year period. RESULTS: Three hundred and sixty residents completed the OITE questionnaire. The journal that was most commonly used by orthopedic residents to prepare for the OITE was the Journal of the American Academy of Orthopedic Surgeons (n = 257, 71%). However, this journal was the third most frequently cited reference for the OITE. Past OITE questions were the highest scored resource with 215 (60%) residents rating them as a 4 ("very useful"). The residents who scored in the top 20% participated in more surgical cases than the other residents (53% vs 35% with 350 or more cases in each group, respectively). CONCLUSIONS: The results of this study suggest that many residents, especially those who do well on the OITE, are using the American Academy of Orthopedic Surgeons self-assessment examinations. The results also support the educational importance of exposure to surgical cases in addition to reading and reviewing journals and/or textbooks.

Evaluation of the Orthopaedic In-Training Examination: spine questions.

BACKGROUND: The annual Orthopaedic In-Training Examination (OITE) is an objective evaluation administered annually to all residents by the American Academy of Orthopaedic Surgeons. To our knowledge, there are no guidelines for the type of material included on the examination; therefore, it is difficult for many academic centers to develop education programs directed toward improving resident performance on the OITE. Our goals were to determine the most commonly tested subjects in the spine portion of the OITE and to help direct development of an associated teaching program. METHODS: We analyzed the number, type, anatomic focus, subject matter, and visual diagnostic modalities of spine questions on the OITEs from 2002 through 2007 and identified the most commonly referenced journals. RESULTS: The average annual number of spine questions was 23.1 (8.4% of the examination). The most common types of spine questions related to knowledge (44.5%), evaluation and decision making (29.1%), and diagnosis (26.3%); the most common subject matters were trauma (15.1%) and anatomy (13.7%). The most frequently examined anatomic locations were the cervical (30.9% of questions) and lumbar (17.4%) spines. General spine information (no anatomic focus) accounted for 31.6% of questions. The most commonly referenced journals were Spine and The Journal of Bone and Joint Surgery, American Volume. CONCLUSIONS: Developing a study plan focusing on these journals and the most commonly tested topics and question types will better prepare orthopedic residents for the spine questions on the OITE.

Analysis of the pediatric orthopedic surgery questions on the Orthopaedic In-Training Examination, 2002 through 2006.

BACKGROUND: Pediatric orthopedics has been a frequently tested topic on the Orthopaedic In-Training Examination (OITE). Our goal was to provide direction for resident education efforts by: (1) analyzing the exam's number, topics, and types of pediatric orthopedic surgery questions; (2) examining references cited in the postexam answer packet supplied by the American Academy of Orthopaedic Surgeons; and (3) examining the efficacy of the Orthopaedic Knowledge Update (OKU): Pediatrics 3 book as a source for answers to the pediatric orthopedic questions. METHODS: We reviewed 5 years (2002 through 2006) of OITEs and the associated American Academy of Orthopaedic Surgeons' answer packets and assessed the OKU: Pediatrics 3 book for topic relativity. Each question was classified into 1 of 6 categories and labeled with a cognitive taxonomy level: 1 (simple recall), 2 (interpretation of data), or 3 (advanced problem-solving). The 6 categories included: (1) pediatric orthopedic knowledge; (2) knowledge of treatment modalities; (3) diagnosis; (4) diagnosis with recognition of associated conditions; (5) diagnosis with further studies; and (6) diagnosis with treatment. RESULTS: The overall percentage of pediatric questions was 14.1%. The most commonly addressed were pediatric elbow fractures, osteomyelitis, and scoliosis. The most common question types were categories 1 (pediatric orthopedic knowledge) and 6 (diagnosis with treatment). The most frequently referenced textbooks were Lovell and Winter's Pediatric Orthopaedics (31%) and Tachdjian's Pediatric Orthopaedics (16%). The most frequently referenced journals were the Journal of Pediatric Orthopaedics (American) (29%) and the Journal of Bone and Joint Surgery (American) (19%). Using only the OKU: Pediatrics 3 review textbook, 65% of the questions could be answered. CONCLUSIONS: Knowledge of the topics more likely to be tested may help the orthopedic educator direct a didactic curriculum geared toward the OITE and American Board of Surgery examinations. Although the OKU: Pediatrics 3 book seems to be a good, concise resource for studying for the board examination and OITE, residents should be encouraged to supplement their studying with primary sources. LEVEL OF EVIDENCE: Not applicable.

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.