Hypoxia-related microRNA-210 is a diagnostic marker for discriminating osteoblastoma and osteosarcoma.

Osteoblastoma is a benign bone tumor that can often be difficult to distinguish from malignant osteosarcoma. Because misdiagnosis can result in unfavorable clinical outcomes, we have investigated microRNAs as potential diagnostic biomarkers for distinguishing between these two tumor types. Next generation RNA sequencing was used as an expression screen to evaluate >2,000 microRNAs present in tissue derived from rare formalin fixed paraffin embedded (FFPE) archival tumor specimens. MicroRNAs displaying the greatest ability to discriminate between these two tumors were validated on an independent tumor set, using qPCR assays. Initial screening by RNA-seq identified four microRNA biomarker candidates. Expression of three miRNAs (miR-451a, miR-144-3p, miR-486-5p) was higher in osteoblastoma, while the miR-210 was elevated in osteosarcoma. Validation of these microRNAs on an independent data set of 22 tumor specimens by qPCR revealed that miR-210 is the most discriminating marker. This microRNA displays low levels of expression across all of the osteoblastoma specimens and robust expression in the majority of the osteosarcoma specimens. Application of these biomarkers to a clinical test case showed that these microRNA biomarkers permit re-classification of a misdiagnosed FFPE tumor sample from osteoblastoma to osteosarcoma. Our findings establish that the hypoxia-related miR-210 is a discriminatory marker that distinguishes between osteoblastoma and osteosarcoma. This discovery provides a complementary molecular approach to support pathological classification of two diagnostically challenging musculoskeletal tumors. Because miR-210 is linked to the cellular hypoxia response, its detection may be linked to well-established pro-angiogenic and metastatic roles of hypoxia in osteosarcomas and other tumor cell types. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1137-1146, 2017.

The Impact of the Immediate Postoperative Prosthesis on Patient Mobility and Quality of Life after Transtibial Amputation.

BACKGROUND: The immediate postoperative prosthesis has been purported to allow early mobilization with potential physical and psychologic benefits to patients. This study used accelerometers and validated questionnaires to prospectively examine activity level and quality of life data for patients receiving an immediate postoperative prosthesis after transtibial amputation. METHODS: A total of 10 patients were included in the study. Mean age was 58 yrs (range, 22-69 yrs), there were 9 men and 1 woman, and reason for amputation was nonhealing gangrenous ulcer in 9 patients and ischemic limb in 1 patient. Patients were followed for 6 wks. Activity data were collected on ActiGraph GT3X accelerometers and analyzed using ActiLife 6 Data Analysis Software. At the 6-wk postoperative visit, an Amputee Mobility Predictor clinician-rated performance evaluation was conducted and a Short Form-36 questionnaire was completed. RESULTS: Patients in the cohort spent an average of 88% (range, 83%-92%) of their time sedentary, 11.5% (range, 7.6%-16.9%) of their time in light physical activity, and 0.3% (range, 0.12%-1.36%) of their time in moderate to vigorous physical activity. No statistically significant relationships were observed between expected level of function and recorded activity level. Patients had low physical and emotional Short Form-36 component scores. CONCLUSIONS: Patients with transtibial amputations were extremely sedentary in the early postoperative period despite their immediate postoperative prosthesis dressings.

Functional outcome measures of patients following hemipelvectomy.

BACKGROUND: Major amputations are indicated for curative treatment of some tumors of the pelvis. Previous literature suggests that patients with a hemipelvectomy amputation are more efficient walking with crutches than using a prosthesis. OBJECTIVES: The purpose of this study was to evaluate whether modern prosthetic use after hemipelvectomy may be a viable option for patients than in the past. STUDY DESIGN: Case control trial. METHODS: We identified five patients who underwent hemipelvectomy amputation and fit with high-level prosthetic components. Patients were evaluated using a timed up and go, 5-m walk, 400-m walk, and stair climb tests to evaluate functional performance with a prosthesis and without. Short Form-36 scores were collected as well. These results were compared to matched controls. RESULTS: There was a trend for faster locomotion using crutches over wearing a prosthesis in the timed up and go, and 5-m and 400-m walk; no difference was seen in stair climbing. Short Form-36 scores showed decreased physical component score, but equal mental component score compared to the general population. CONCLUSION: Our results show that in addition to advances in surgical techniques, prosthetic rehabilitation and management are beginning to optimize functional mobility with the prosthesis. CLINICAL RELEVANCE: Patients who use a modern prosthesis following hemipelvectomy demonstrated good clinical function with and without their prosthesis. Although health status scores were decreased in the physical component, mental component scores were equal to healthy controls.

Prosthetic Rehabilitation After Hip Disarticulation or Hemipelvectomy.

OBJECTIVE: Prosthetic rehabilitation after pelvic-level amputation (hemipelvectomy/hip disarticulation) is difficult, and because of this, many patients are never fit with a prosthetic limb. The objectives of the study were to evaluate the characteristics of successful prosthetic users and to determine what factors are associated with successful prosthetic fitting and use. DESIGN: The authors identified 43 patients who underwent hip disarticulation/hemipelvectomy between 2000 and 2010 and were candidates for prosthetic fitting at the authors' institution. The medical records of these patients were then reviewed for pertinent demographic and medical characteristics to identify the profile of successful prosthetic users. RESULTS: Of 43 patients, 18 (43%) successfully used a prosthetic limb. The only preoperative factor associated with unsuccessful prosthetic fitting was coronary artery disease. Specifically, age, body mass index, other medical comorbidities, and demographic characteristics were not associated with successful or unsuccessful prosthetic fitting. Successful users wore their prosthesis an average of 5.8 hrs/day, and most ambulated with one or both hands free. CONCLUSIONS: Successful prosthetic rehabilitation after hemipelvectomy and hip disarticulation is possible. Increased body mass index, advanced age, depression, and other comorbidities should not discourage prosthetic rehabilitation. Most patients that undergo prosthetic rehabilitation enjoy long periods of survival and wear their prosthesis for most of the day.

Prosthetic fitting after rotationplasty of the knee.

OBJECTIVE: The objectives of this study were to describe the authors' experience with the timeline for prosthetic fitting after rotationplasty of the knee and to determine factors that may be associated with earlier prosthetic fitting. DESIGN: The authors conducted a retrospective observational study of 12 patients who underwent rotationplasty of the knee and received prosthetic care at this institution. All patients had oncologic causes for surgery. RESULTS: The median age at amputation was 10 yrs. The overall survival rate was 92%. Five patients received a preliminary bypass prosthesis. All 12 patients were successfully fitted with a definitive prosthesis. Three patients were fitted within 90 days; two of these three patients did not require chemotherapy. The median time for definitive prosthetic fitting in the ten patients requiring chemotherapy was 230.5 days (range, 85-425 days). Nine patients had documentation supporting a return to sport/premorbid physical recreational activities. CONCLUSIONS: In the authors' experience, chemotherapy was associated with delayed definitive prosthetic fitting. Typically, the patients who required rotationplasty for cancer completed fitting with a definitive prosthesis in 6 mos. The findings of this study validate previous reports and confirm that most rotationplasty patients have excellent outcomes with return to premorbid physical activities.

Noninvasive arterial studies including transcutaneous oxygen pressure measurements with the limbs elevated or dependent to predict healing after partial foot amputation.

OBJECTIVE: Noninvasive arterial studies have been used to determine level of amputation. The objective of this study was to examine each component of the noninvasive arterial studies to determine optimal cut points to predict healing and to evaluate whether physiologic maneuvers could improve the utility of transcutaneous oxygen pressure (TcPO2) values to predict healing of partial foot amputation. DESIGN: The authors conducted a retrospective, observational study of 307 patients who underwent partial foot amputation and had noninvasive arterial studies in the perioperative period. RESULTS: The TcPO2 values were significantly predictive of healing. Specifically, a cut point TcPO2 value of 38 mm Hg had a sensitivity and a specificity of 71% for predicting healing or failure. The optimal cut point was mostly unaffected by patient characteristics. The addition of noninvasive arterial studies recorded in a position with the limb elevated improved prediction in the subgroup with supine TcPO2 values of 38 mm Hg or lower. CONCLUSIONS: The findings of this study validate previous reports and confirm that TcPO2 measurements are valuable to more accurately determine the correct amputation level and, in turn, obtain better outcomes. TcPO2 measurements may provide better prognostic value than do ankle-brachial indices for healing after partial foot amputation. TcPO2 measurements are useful but should not be used in isolation to make treatment decisions regarding amputation level.

Reconstruction of the proximal humerus for bone neoplasm using an anatomic prosthesis-bone graft composite.

This study assesses function after limb sparing bone tumour resections of the proximal humerus. Twenty-seven patients had an intraarticular resection with reconstruction using an anatomic prosthesis-bone graft composite with average clinical follow-up of 63 years (range: 13-15.8 years). Pain relief was achieved for 22 shoulders (81%); 19 of 25 patients responding (76%) were satisfied. Active elevation averaged 62 degrees, external rotation 25 degrees, and internal rotation to L-4. Complications included instability in 7, nonunion in 4, implant loosening in 3 of these and tumour recurrence in 1. There were 7 reoperations. Using the Neer rating, 19 primary operations (70%) were successful. The Musculoskeletal Tumor Society Score averaged 18.5 (62%), the American Shoulder and Elbow Surgeons functional score 18.4 (37%) with a total score of 51 (51%), and on the Simple Shoulder Test 5.4 of 12 questions were answered affirmatively. This procedure is oncologically safe. There are structural complications, notably shoulder instability. Function ratings are one-third to one-half normal.

The effect of obstructive sleep apnea on amputation site healing.

Obstructive sleep apnea (OSA) is an independent risk for hypertension, cerebral artery stenosis, stroke and hypercoagulability.(1) Our research objective was to assess whether sleep disordered breathing affects the peripheral circulation, decreases perfusion as measured by TcPO2 and decreases the odds that a partial-foot amputation site will heal. We hypothesized that OSA would be an independent risk factor causing delayed healing of partial-foot amputations. We conducted a retrospective, observational study on a total of 307 patients who had TcPO2 measurements and underwent partial-foot amputation. Twenty-five of these patients had OSA. In our study, patients with OSA had a 3.7-fold increase in odds of healing within 3 months in comparison with patients without OSA. Of note, 16 patients (64%) with OSA were not treated with continuous positive airway pressure (CPAP) and healed within 3 months. Our results do not support our hypothesis that the presence of sleep apnea may impair healing of partial foot amputations. Further studies are needed to fully determine the effect of OSA and its treatment on TcPO2s and healing.

Chondroblastoma with secondary aneurysmal bone cyst of the hamate: case report.

Chondroblastoma of the carpals is rare, can mimic other benign bone tumors, and presents a diagnostic challenge. There have been few cases of benign tumors involving the hamate, with only one reported case of chondroblastoma, which was treated with complete hamate excision. We present a case of chondroblastoma with secondary aneurysmal bone cyst of the hamate treated with curettage, high-speed burring, phenol, and autogenous iliac crest bone grafting. At the time of the most recent radiographic follow-up, there was full graft incorporation, preserved hamate morphology, and no evidence of recurrence.

Multicentric giant cell tumor of the upper extremities: 16 years of ongoing disease.

Multicentric giant cell tumor is rare and accounts for less than 1% of all giant cell tumors of bone. We describe a case in which all the lesions occurred in the upper extremities. The 13-year-old boy's first tumor was in the left index metacarpal. Over 16 years, giant cell tumors occurred in 8 sites: right distal radius, left lunate, left middle metacarpal, left distal radius, right ring finger proximal phalanx, right radial head, left distal humerus, and left proximal humerus. Intralesional curettage of the lesions located in the hand and carpals was associated with a high incidence of local recurrence, whereas lesions in the proximal radius and in the humerus have not recurred.

Mayo Clinic consensus recommendations for the depth of excision in primary cutaneous melanoma.

Currently, no data from randomized controlled clinical trials are available to guide the depth of resection for intermediate-thickness primary cutaneous melanoma. Thus, we hypothesized that substantial variability exists in this aspect of surgical care. We have summarized the literature regarding depth of resection and report the results of our survey of surgeons who treat melanoma. Most of the 320 respondents resected down to, but did not include, the muscular fascia (extremity, 71%; trunk, 66%; and head and neck, 62%). However, significant variation exists. We identified variability in our own practice and have elected to standardize this common aspect of routine surgical care across our institution. In light of the lack of evidence to support resection of the deep muscular fascia, we have elected to preserve the muscular fascia as a matter of routine, except when a deep primary melanoma or thin subcutaneous tissue dictates otherwise.

Thirty-year follow-up of patient with Gorham disease (massive osteolysis) treated with hip arthroplasty.

Gorham disease (also known as massive osteolysis or disappearing bone disease) is an exceedingly rare, peculiar entity of uncertain cause and unpredictable prognosis. There is no proven mode of therapy or consensus on treatment. We present 30-year follow-up on a patient successfully treated with resection, total hip arthroplasty, and radiation with no recurrence of disease. Our observations in this case suggest that surgical treatment and reconstruction can lead to good long-term function and disease-free survival.

Angiomatoid fibrous histiocytoma in a 25-year-old male.

Angiomatoid fibrous histiocytoma (AFH) is a rare disease that is often misdiagnosed initially. Patients can present with a clinical picture concerning for other diseases, and pathologic review is not always revealing. Molecular diagnostics are increasingly being utilized to detect gene fusions characteristic for AFH. Surgery remains the mainstay of management, and can effectively control local recurrences and metastases. Herein we describe a case report of a 25-year-old gentleman whose presentation was concerning for lymphoma. Subsequently we review of the relevant literature.

Does the second-generation intercalary humeral spacer improve on the first?

UNLABELLED: Since publication of the results of a first-generation intercalary humeral spacer, a newer design has been available that addressed the weaknesses of the first. This study evaluated the hypothesis that the second-generation lap joint junction intercalary humeral spacer reduced complications compared with the original male-female taper design. We retrospectively reviewed the charts of 32 consecutive patients who had undergone placement of an intercalary humeral spacer. Twenty-one with the male-female taper (minimum followup 0 months, mean 19.2 months) were compared with 11 with the lap joint configuration (minimum followup 0 months, mean 20.3 months). Demographic, tumor, treatment, and radiographic variables were similar between groups. We observed a lower complication rate in the lap joint group (three of 11 versus 11 of 21). The most common complications in the male-female group, neuropraxia, periprosthetic fracture, and disengagement, were not seen in the lap joint group. Aseptic loosening was more frequent in the lap joint group. There were no differences in blood loss, operative time, or Musculoskeletal Tumor Society scores between groups. We noted improvement in Musculoskeletal Tumor Society scores from preoperatively to postoperatively in both groups. Use of these implants should be reserved for patients with limited life expectancy. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Synovial chondromatosis of the foot and ankle.

BACKGROUND: Synovial chondromatosis (SC) is a benign condition where the synovial lining of joints, bursae, or tendon sheaths undergoes metaplasia and ultimately forms cartilaginous loose bodies. Synovial chondromatosis of the foot and ankle is exceedingly rare, and outcomes following surgical excision are largely unknown. MATERIALS AND METHODS: An Institutional Review Board-approved retrospective review of our institution's surgical database from 1970 to 2006 revealed 8 patients with SC of the foot and/or ankle confirmed by pathology. RESULTS: Eight patients (4 female and 4 male) presented with pain, locking, or stiffness. Average age at presentation was 37 (range, 19 to 60) years. Average followup was 9.5 (range, 1 to 31) years. Six patients had involvement of the ankle, and two, the midfoot. Four patients underwent ankle synovectomy with loose body removal, and were pain-free at last followup. One patient underwent excision and midfoot arthrodesis for severe midfoot destruction. Three patients ultimately underwent below knee amputation, one for multiple recurrences and two for malignant transformation to low-grade chondrosarcoma. CONCLUSION: To our knowledge, this is the largest reported series of patients with SC of the foot and ankle. In half the patients, synovectomy with excision of loose bodies resulted in pain free return to normal function, without recurrence, at last followup. However, recurrence occurred in 3 (37.5%) of 8 patients with subsequent malignant transformation to low-grade chondrosarcoma occurring in 2 patients.

Oncogenic osteomalacia: localization of underlying peripheral mesenchymal tumors with use of Tc 99m sestamibi scintigraphy.

OBJECTIVE: To highlight a strategy for potential detection of mesenchymal tumors in oncogenic malacia, as illustrated by 3 cases. METHODS: Three case reports are presented in which successful localization of the offending neoplasm was accomplished by using whole-body Tc 99m sestamibi scanning. Alternative localization techniques are also reviewed. RESULTS: Oncogenic osteomalacia occurs infrequently and is caused by neoplasms that secrete phosphatonins, substances that interfere with proximal tubular resorption of phosphorus and can result in phosphaturia, hypophosphatemia, reduced 1,25-dihydroxyvitamin D concentration, and osteomalacia. Removal of the underlying neoplasm results in complete resolution of all biochemical, pathologic, and physical manifestations of this disorder, as shown in our 3 patients. Because the neoplasms are small and can occur in any tissue compartment, they are difficult to localize, a feature that often results in therapeutic failure. CONCLUSION: We conclude that use of whole-body Tc 99m sestamibi scanning may be an appropriate and cost-effective initial strategy for the localization of peripheral phosphatonin-secreting tumors.

Arthroscopic technique for treatment of synovial chondromatosis of the glenohumeral joint.

Synovial chondromatosis of the shoulder has been treated in the past with an open arthrotomy, removal of loose bodies, and synovectomy. Several authors have described arthroscopy as a means of treating this rare disorder because of the excellent visualization of the glenohumeral joint, decreased morbidity, and early rehabilitation potential. This article offers a technique in which a large-bore cannula and high pressure and flow are used to facilitate the removal of loose bodies from the joint.

Scapular chondrosarcomas have high rates of local recurrence and metastasis.

This is the first report of a large series of patients with scapular chondrosarcomas. The grade distributions, locations of the tumors in the scapula, surgical techniques, status of margins, chondrosarcoma subtypes, Enneking stages, adjuvant therapies, local recurrence rates, metastasis rates, and survival prognoses of patients with scapular chondrosarcoma were evaluated. Forty-seven patients treated between 1921 and 1999 were analyzed retrospectively. Grade 3 disease was significantly associated with a poorer survival prognosis when compared with Grades 1 or 2 disease. Patients with tumors smaller than 5 cm were treated mainly with partial scapulectomy, and patients with tumors larger than 5 cm often were treated with total scapulectomy. The survival prognoses of patients with intralesional resections at initial surgery showed a tendency toward poorer survival when compared with patients with wide resections at initial surgery. Metastasis and local recurrence (21.3% and 40.4%) were higher in scapular chondrosarcomas than rates reported for patients with general chondrosarcomas, and local recurrence or metastasis was associated with limited survival. The 5- and 15-year survival probabilities subsequent to diagnosis were 79% and 53%, respectively. The high rates of local recurrence and metastasis likely were caused by the difficult anatomic relationships encountered during scapular resections. This study shows the importance of wide margins which must be achieved to provide local disease control.

Primary vertebral osteosarcoma: imaging findings.

PURPOSE: To evaluate patient age and sex and location and imaging appearances of primary vertebral osteosarcoma (PVOS) compared with histologic subtypes. MATERIALS AND METHODS: Retrospective review (1915-2001) of imaging findings in patients with histologically proved primary osteosarcoma of vertebral column was performed. Two radiologists in consensus reviewed findings for location, origin site, matrix pattern, and spinal canal invasion and compared them with histologic subtypes. Radiation-induced, Paget, metastatic, and multifocal osteosarcoma were excluded. RESULTS: Of 4,887 osteosarcoma cases, 198 (4%) were PVOS arising from vertebral column. There were 103 female and 95 male patients (age range, 8-80 years; median age, 34.5 years). Involvement included cervical (27 patients), thoracic (66 patients), lumbar (64 patients), and sacral (41 patients) spine. Adequate imaging findings were available in 69 patients, and involvement of two levels was seen in 12 (17%). In nonsacral spine, most tumors (44 cases) arose from posterior elements, with partial involvement of vertebral body. Lesions confined to vertebral body were less frequent (12 cases). Sacral tumors involved body and sacral ala. The most common histologic subtypes were osteoblastic (47 patients), chondroblastic (12 patients), telangiectatic (four patients), fibroblastic (four patients), small cell (one patient), and epithelioid (one patient). The majority (55 cases) demonstrated osteoid matrix mineralization; 17 showed marked mineralization. Five cases with marked mineralization were confined to vertebral body, with "ivory vertebra" appearance. Purely lytic pattern was seen in 14 (20%) cases. Lytic pattern was seen in four (100%) telangiectatic, three (75%) fibroblastic, three (25%) chondroblastic, three (6%) conventional osteoblastic, and one (100%) small-cell subtypes. Invasion of spinal canal was common (84% of cases). Appearance simulating osteoblastoma without soft-tissue mass was present (seven cases). Pathologic compression fractures were identified (seven patients). CONCLUSION: This study provides age and sex distribution and location and imaging features in a large series of PVOS.