Shekhar M. Kumta

Imaging of musculoskeletal tuberculosis: a new look at an old disease.

There are certain imaging features that help to differentiate tuberculosis from other bone and joint disorders with a similar presentation. The current authors discuss these distinguishing imaging features particularly with respect to ultrasound, computed tomography, and magnetic resonance imaging. The judicious and appropriate use of these newer imaging modalities coupled with aspiration or biopsy can lead to earlier recognition of musculoskeletal tuberculosis before the onset of debilitating disease.

Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions.

This study aims to investigate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in giant cell tumor of bone (GCT) and other osteolytic lesions in bone. By using semi-quantitative RT-PCR, we showed that three major isoforms of VEGF (121, 165 and 189) were expressed in GCTs, with isoform 121 being the most abundant. The expression levels of VEGF and MMP-9 mRNA were significantly higher in advanced GCTs (stage II/III) than in stage I GCTs. We further elucidated the cellular localization of VEGF and MMP-9 gene transcripts in GCT and other osteolytic lesions using an in situ hybridization assay. The results showed that stromal tumor cells and osteoclast-like giant cells of GCT, fibrous stromal cells in anuerysmal bone cysts and fibrous dysplasia, and Langerhans-type giant cells as well as histocytes in eosinophillic granuloma, were all strongly positive for VEGF and MMP-9 mRNA expression. In a prospective study, we performed VEGF and MMP-9 immuno-staining on paraffin sections of pathological tissues harvested from 48 patients (14 GCT, 10 anuerysmal bone cysts, 10 eosinophillic granuloma, 4 fibrous dysplasia, 2 simple bone cyst, 2 osteomyelitis and 6 patients with fractured femoral head as control). The results showed that the differences in VEGF and MMP-9 expression between Stage I and other advanced Stages (II, III and recurrent) were highly significant (p<0.001), with advanced stages showing a higher mean expression. The difference between recurrent and Stage II and III lesions, was also statistically significant (p=0.03 for VEGF, and p=0.01 for MMP-9 expression), with recurrent lesions showing a higher mean expression of both VEGF and MMP-9. In conclusion, VEGF and MMP-9 expression in osteolytic lesions of bone co-relates well with the extent of bone destruction and local recurrence. Their expression may therefore provide some prognostic indication of the possible aggressive behavior of the underlying pathology.

Precision tumour resection and reconstruction using image-guided computer navigation

The use of a navigation system in musculoskeletal tumour surgery enables the integration of pre-operative CT and MRI images to generate a precise three-dimensional anatomical model of the site and the extent of the tumour. We carried out six consecutive resections of musculoskeletal tumour in five patients using an existing commercial computer navigation system. There were three women and two men with a mean age of 41 years (24 to 47). Reconstruction was performed using a tumour prosthesis in three lesions and a vascularised fibular graft in one. No reconstruction was needed in two cases. The mean follow-up was 6.9 months (3.5 to 10). The mean duration of surgery was 28 minutes (13 to 50). Examination of the resected specimens showed clear margins in all the tumour lesions and a resection that was exactly as planned.

Computer assisted pelvic tumor resection and reconstruction with a custom-made prosthesis using an innovative adaptation and its validation.

Computer aided musculoskeletal tumor surgery is a novel concept. Ideally, computer navigation enables the integration of preoperative information concerning tumor extent and regional anatomy to facilitate execution of a surgical resection. Accurate resection helps oncological clearance and facilitates precise fitting of a custom prosthesis. We adapted a commercially available computer navigation platform for spine, and used it to plan and execute pelvic bone resection and custom pelvic prosthetic reconstruction in a patient with a metastatic tumor affecting the acetabulum. The surgery was simulated and validated using a plaster bone model based on the patients preoperative CT data, before performing the procedure on the patient.

Chronic recurrent multifocal osteomyelitis: a great clinical and radiologic mimic in need of recognition by the pathologist.

The spectrum of histopathologic changes in four cases of chronic recurrent multifocal osteomyelitis encountered in our orthopedic outpatient clinic in the past 3 years was studied in conjunction with clinical and radiologic findings. All presented with pain with or without swelling in the affected region. Radiographically, the appearance of the lesions varied from a mixed picture of bone lysis and sclerosis with expansion to sclerosis alone to bone collapse. Bone scintigraphy demonstrated asymptomatic and separate foci of activity in all cases. Prior to biopsy, the clinical and radiologic differential diagnoses included Ewings sarcoma, metastatic neuroblastoma, hematolymphoid malignancy, Langerhans cell histiocytosis and chronic infection, notably tuberculosis. The spectrum of histopathologic changes ranged from acute (acute inflammatory infiltration, active bone resorption and necrosis, reactive bone formation) to subacute (predominantly lymphocytic and plasma cell infiltration) to chronic inflammation (fibroblastic organization and bony sclerosis). Histologic changes correlated poorly with clinical features, but relatively well with radiologic findings. Lesional excision was performed in one case, cortical saucerization in another, while the final two cases received supportive treatment. All remained well 18–21 months post‐therapy. Chronic recurrent multifocal osteomyelitis is a great clinical and radiologic mimic, which merits recognition by the pathologist. Awareness of the spectrum of histologic features encountered enables a correct diagnosis to be made in the appropriate clinical setting. The patient can thus be reassured of a favorable prognosis.

Joint-preserving Tumor Resection and Reconstruction Using Image-guided Computer Navigation

BackgroundJoint-preserving surgery is performed in select patients with bone sarcomas of extremities and allows patients to retain the native joint with better joint function. However, recurrences may relate to achieving adequate margins and there is frequently little room for error in tumors close to the joint surface. Further, the tumor margin on preoperative CT and/or MR images is difficult to transpose to the actual extent of tumor in the bone in the operating room.Questions/purposesWe therefore determined whether joint-preserving tumor surgery could be performed accurately under image-guided computer navigation and determined local recurrences, function, and complications.MethodsWe retrospectively studied eight patients with bone sarcoma of extremities treated surgically by navigation with fused CT-MR images. We assessed the accuracy of resection in six patients by comparing the cross sections at the resection plane with complementary prosthesis templates. Mean age was 17 years (range, 6–46 years). Minimum followup was 25 months (mean, 41 months; range, 25–60 months).ResultsThe achieved resection was accurate, with a difference of 2 mm or less in any dimension compared to that planned in patients with custom prostheses. We noted no local recurrence at latest followup. The mean Musculoskeletal Tumor Society score was 29 (range, 28–30). There were no complications related to navigation planning and procedures. There was no failure of fixation at the remaining epiphysis.ConclusionsIn selected patients, the computer-assisted approach facilitates precise planning and execution of joint-preserving tumor resection and reconstruction. Further followup assessment in a larger study population is required in these patients.Level of EvidenceLevel IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Alveolar soft-part sarcoma: a rare soft-tissue malignancy with distinctive clinical and radiological features

Abstract Alveolar soft-part sarcoma (ASPS) is a rare tumour. Certain distinctive clinical and radiological features suggest the correct diagnosis. There is moderate predilection for young women. ASPS almost always arises in skeletal muscle and occurs most frequently in the lower limbs. There is often a long clinical history and a large mass at presentation. Two young females with ASPS presented with very vascular tumours in the thigh, with prominent intra- and extra-tumoural blood vessels. The imaging findings and the existing literature are reviewed.

Absorbable intramedullary implants for hand fractures. Animal experiments and clinical trial

Biodegradable implants made from polyglycolic and polylactic acid co-polymers undergo degradation by hydrolysis which results in loss of their mechanical strength. The degradation of 1.5 mm polyglycolide rods (Biofix) was studied after intramedullary and subcutaneous implantation in rabbits. Two weeks after implantation there was a 73% reduction in strength of the intramedullary implants and a 64% reduction in the subcutaneous implants. Polyglycolide implants were compared with Kirschner wires for intramedullary fixation of extra-articular fractures in the hand. In one group of patients fractures were fixed with a 1.5 mm intramedullary rod and in a similar group a Kirschner wire was used. In both a wire loop was added for extra fixation. At six months there was no significant difference between the two groups. There were no allergic reactions to the polyglycolide implants.

Comparison of the anti-tumor effects of denosumab and zoledronic acid on the neoplastic stromal cells of giant cell tumor of bone

Abstract Denosumab and Zoledronic acid (ZOL) are two antiresorptive drugs currently in use for treating osteoporosis. They have different mechanisms of action but both have been shown to delay the onset of skeletal-related events in patients with giant cell tumor of bone (GCT). However, the anti-tumor mechanisms of denosumab on the neoplastic GCT stromal cells remain unknown. In this study, we focused on the direct effects of denosumab on the neoplastic GCT stromal cells and compared with ZOL. The microscopic view demonstrated a reduced cell growth in ZOL-treated but not in denosumab-treated GCT stromal cells. ZOL was found to exhibit a dose-dependent inhibition in cell growth in all GCT stromal cell lines tested and cause apoptosis in two out of three cell lines. In contrast, denosumab only exerted a minimal inhibitory effect in one cell line and did not induce any apoptosis. ZOL significantly inhibited the mRNA expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) in two GCT stromal cell lines whereas their protein levels remained unchanged. On the contrary, denosumab did not regulate RANKL and OPG expression at both mRNA and protein levels. Moreover, the protein expression of Macrophage Colony-Stimulating Factor (M-CSF), Alkaline Phosphatase (ALP), and Collagen α1 Type I were not regulated by denosumab and ZOL either. Our findings provide new insights in the anti-tumor effect of denosumab on GCT stromal cells and raise a concern that tumor recurrence may occur after the withdrawal of the drug.

Use of a patient-specific CAD/CAM surgical jig in extremity bone tumor resection and custom prosthetic reconstruction

Computer navigation has recently been introduced for bone tumor surgery in the orthopedic field, with the aim of achieving increased accuracy and precision in tumor resection and in custom prosthetic reconstruction. However, the technique requires bulky navigation facilities, the presence of a system operator in the operating room, and surgeons with prior experience in navigated surgery. We describe a new and simple method of using a patient-specific computer-aided design/computer-aided modeling (CAD/CAM) surgical jig to realize the preoperative planning in the surgical field. The accuracy of the proposed method was first tested in a cadaver trial. It took one minute to set the location of the jig prior to the bone resection and three minutes to perform the bone resections via the cutting slits of the jig. The dimensional difference between the achieved and planned bone resection was <1 mm on validation with the help of a junctional plate and a navigation system. The technique was then applied successfully to a patient with a low-grade osteosarcoma of the femur. An intercalated tumor resection was performed using a patient-specific surgical jig, and a custom CAD prosthesis reconstruction matched accurately to the skeletal defect. Further assessment in a larger population is necessary to determine the clinical efficacy of the technique.