Shishir Rastogi

In Vivo Efficacy of Antimicrobial-Coated Devices

BACKGROUND Since device colonization is a prelude to infection, an antimicrobial-coated device that reduces bacterial colonization can potentially protect against infection. The objective of this animal study was to assess the efficacy of a coating with minocycline and rifampin to prevent colonization of a grit-blasted titanium implant and subsequent osteomyelitis. METHODS Twenty-five rabbits underwent implantation of a titanium-alloy pin, either coated with minocycline and rifampin (thirteen rabbits) or uncoated (twelve rabbits), into the right femoral medullary canal. The implanted devices were inoculated with 500 CFU (colony-forming units) of Staphylococcus aureus prior to wound closure. The rabbits were killed one week later, and the removed device, femoral bone, a specimen obtained by swabbing the track surrounding the device, and blood were cultured. The rates of device colonization, osteomyelitis, and device-related osteomyelitis were compared between the two groups of rabbits. RESULTS The antimicrobial-coated devices had a significantly lower rate of colonization than the uncoated devices (five of thirteen compared with twelve of twelve, p = 0.0016) and were associated with significantly lower rates of osteomyelitis (six of thirteen compared with twelve of twelve, p = 0.005) and device-related osteomyelitis (five of thirteen compared with twelve of twelve, p = 0.0016). Bacteremia did not develop in any rabbit. CONCLUSIONS Orthopaedic devices coated with minocycline and rifampin significantly protected against device colonization and infection due to Staphylococcus aureus in this in vivo rabbit model. CLINICAL RELEVANCE It is possible that orthopaedic devices coated with this unique combination of antimicrobial agents may protect against the development of clinical infection in humans.

Tuberculosis of the foot

In 44 patients with tuberculosis of the foot we identified five radiological patterns of lesions; cystic, rheumatoid, subperiosteal, kissing and spina ventosa. Cystic destruction had the best outcome and rheumatoid the poorest. All the patients were cured after antituberculous treatment for 18 months, and none required surgery.

Treatment of aneurysmal bone cysts with percutaneous sclerotherapy using polidocanol: A REVIEW OF 72 CASES WITH LONG-TERM FOLLOW-UP

Aneurysmal bone cyst is a rare tumour-like lesion which develops during growth. Our aim was to determine the efficacy of the administration of percutaneous intralesional 3% polidocanol (hydroxypolyaethoxydodecan) as sclerotherapy. Between July 1997 and December 2004 we treated 72 patients (46 males, 26 females) with a histologically-proven diagnosis of aneurysmal bone cyst, at various skeletal sites using this method. The sclerotherapy was performed under fluoroscopic guidance and general anaesthesia or sedation and local anaesthesia. The mean follow-up period was 34 months (26.5 to 80). The patients were evaluated using the Enneking system for functional assessment and all the lesions were radiologically quantified into four grades. The mean age of patients was 15.6 years (3 to 38) and the mean number of injections was three (1 to 5). Ten patients were cured by a single injection. The mean reduction in size of the lesion (radiological healing) was found to be 76.6% (61.9% to 93.2%) with a mean clinical response of 84.5% (73.4% to 100%). Recurrence was seen in two patients (2.8%) within two years of treatment and both were treated successfully by further sclerotherapy. Percutaneous sclerotherapy with polidocanol is a safe alternative to conventional surgery for the treatment of an aneurysmal bone cyst. It can be used at surgically-inaccessible sites and treatment can be performed on an out-patient basis.

Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

BackgroundHistological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy.ObjectiveTo establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease.Materials and methodsThirty-one treatment-naïve osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006–2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out.ResultsBoth pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume.ConclusionIn osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma.

VEGF expression as a prognostic marker in osteosarcoma.

The vascular endothelial growth factor (VEGF) pathway is the key regulator of angiogenesis. In osteosarcoma baseline VEGF is of proven prognostic value but prognostic potential of post‐NACT VEGF expression is largely unexplored.

Autism Speaks: meeting on folate metabolism and Autism spectrum disorders, March 19-20, 2009, Washington, DC.

OBJECTIVES Some children treated for acute lymphoblastic leukemia (ALL) experience delayed neurocognitive effects similar to autism, which we hypothesize to at least in part be a result of a disruption of folate metabolism due to treatment with an antifolate such as methotrexate. The objectives of this meeting are to review research on the neurocognitive effects of disruption of folate metabolism, to explore the possible role of folate metabolism in autism, and to propose potential avenues of research for further elucidating this role. This meeting was graciously hosted by Autism Speaks and organized by Dr Barton Kamen who at the time was the Chief Medical Officer of the Leukemia & Lymphoma Society and Dr Leanne Chukoskie. Notes from the meeting were recorded by Marcy Ray. The summary of the talks presented here was edited by Drs Kamen and Chukoskie with the help of some of the participants.BACKGROUND The current standard for neoadjuvant chemotherapy (NACT) response evaluation in osteosarcoma is histopathologic necrosis (HN). However, it is accessible only after NACT completion and may get affected by confounding factors. Thus, noninvasive surrogate such as (18)Fluorine-Fluorodeoxyglucose-positron emission tomography-computerized tomography (PET-CT) scan would be useful to individualize therapy. METHODS Thirty-one treatment naive osteosarcoma patients evaluated prospectively by PET-CT scan preceding and after 3 cycles of NACT and surgery during 2006 to 2008. Various anatomic and metabolic parameters of PET-CT scan were compared with HN (good response ≥90% HN) as reference standard. Receiver operating characteristic curves were generated to assess the best threshold and predictability. RESULTS Median age was 17 years; 25 were male patients and 23 were nonmetastatic. Ten cases were good, whereas 21 cases were poor histologic responders. PET-CT parameters including post-NACT (2) and pre-NACT (1) standard uptake value (SUV)max ratio (SUV2:SUV1), SUV2, pre-NACT and post-NACT volumes (V1and V2), change in V after NACT, pre-NACT and post-NACT metabolic burden (MB) and change in MB after NACT correlated with HN. Two independent predictors were identified in stepwise multivariable analysis; if V1 ≤300 mL and SUV2:SUV1 ≤0.48, observed good histologic response proportions was 83%, whereas if V1 >300 mL and SUV2:SUV1 >0.48, it was 0%. CONCLUSIONS NACT response can be predicted reliably by PET-CT scan early in disease course (even at baseline) and PET-CT parameters correlate well with HN. MB seems to be sensitive substitute for response evaluation. Independent predictors may have wider clinical applications if further validation can be done.

Role of vascular endothelial growth factor as a tumour marker in osteosarcoma: a prospective study

PurposeA prospective study was undertaken to evaluate the diagnostic and prognostic significance of serum levels of vascular endothelial growth factor (VEGF) in patients with primary localised osteosarcoma.MethodsSerum VEGF levels were measured by an enzyme-linked immunosorbent assay (ELISA) in blood samples collected prechemotherapy, postchemotherapy, and postsurgery in 40 patients with histologically proven primary osteosarcoma. Comparison was made between serum VEGF level of healthy controls (n = 10) and prechemotherapy patient sera to evaluate its diagnostic potential. Serum VEGF levels of patients with and without metastasis were compared. Immunohistochemical staining was done to establish the correlation between serum and tissue VEGF expression. The Kaplan–Meier curve was used for survival analysisResultsNo significant relationship was observed between serum VEGF levels and age, gender, tumour size, local recurrence or histopathological subtypes of osteosarcoma. We observed significantly raised mean serum VEGF in patient sera compared with healthy controls (p = 0.001). Significant fall in mean serum VEGF level was observed following chemotherapy (p = 0.001). Patients who developed metastases had significantly higher serum VEGF levels compared with the nonmetastatic group (P = 0.001). Serum VEGF levels correlated well with VEGF expression in tissues.ConclusionSerum VEGF levels might prove to be of diagnostic, predictive and prognostic value in patients with primary osteosarcoma, although further studies with larger sample size and longer follow-up is needed to support the hypothesis.

Her-2/neu, p-53, and their coexpression in osteosarcoma.

Background There is controversy regarding the patterns and prognostic significance of Her-2/neu and p-53 expression in osteosarcoma. Further, their combined expression has not been studied. Procedure Prechemotherapy biopsy specimens of 63 osteosarcoma patients from June 2004 to August 2006 were analyzed for Her-2/neu and p-53 using immunohistochemistry and compared with grade, stage, and morphologic subtype of tumor. Results There were 59 high-grade tumors; 32 of 63 had metastases. Histopathologic types included 36 of 63 osteoblastic and 18 of 63 chondroblastic subtypes. Male sex (P=0.045) and chondroblastic type (P=0.004) were associated with metastatic disease. Her-2/neu cytoplasmic staining was seen in 30 of 63 (47.1%) cases, 4 of 30 had additional membranous staining, 17 of 30 were metastatic, and 29 of 30 were high-grade tumors. Staining grade was 3+ in 10 of 30 samples whereas staining intensity 3+ was observed in 26 of 30 samples. Her-2/neu 3+ staining grade was significantly associated with chondroblastic subtype (6/18, P=0.026). P-53 staining was seen in 20 of 63 (31.74%) cases (all high grade), of which 11 were metastatic. Staining grades 3+ and 4+ were seen in 16 of 20 samples whereas staining intensity 3+ in 13 of 20 samples. P-53 expression was higher in chondroblastic (7/18, P value was not significant) and fibroblastic (3/3, P<0.05) subtypes. Coexpression of Her-2/neu and p-53 was seen in 10 cases (15.87%); 3 of 10 cases showed Her-2/neu membranous staining (P=0.01). Conclusions Her-2/neu (47.1%), p-53 (31.74%), and their combined expression (15.87%) were not related to grade or stage of tumor. Chondroblastic subtype was associated with staining grade 3+ of Her-2/neu staining whereas coexpression of Her-2/neu and p-53 was significantly associated with membranous Her-2/neu staining.

Giant cell tumor of bone: Is curettage the answer?

Background: Giant cell tumors (GCT) are neoplasms of mesenchymal stromal cells with varied manifestations. There is no uniform accepted treatment protocol for these tumors, Materials and Methods: 49 cases of proven giant cell tumors of appendicular skeleton, 27 prospective and 22 retrospective constituteed this study. The retrospective cases were collected by using computerized data base collection method. The patients were evaluated clinically, radiologically and by histology. Companacci grading and Enneking staging was used in the study. Two treatment modalities were used a) extended curettage (with/ without bone grafting/ cementation) or b) wide excision and reconstruction with a prosthesis or arthrodesis. Functional evaluation was done by Ennekings system. Chi square tests, mann-whitney test and ANOVA were used for statistical analysis. Results: The average age was 26.82 years (16-50 years). 25 patients (51%) were recurrent GCT at presentation. The commonest site was lower end of femur (16 cases, 32.65%) and upper end of tibia (13 cases, 26.53%). 40 (81.63%) tumors had less than 5 mm of subchondral bone free of tumor. 35 (71.43%) tumors were Ennekings surgical stage III and companacci grade III. Pathological fractures were seen in 12 (24.49%) cases. Intra-lesional currettage was used in 28 and enbloc excision in 19 patients and 2 (4.08%) underwent amputation. The average follow up period was 18.6 months (range 2-84). One recurrence was seen in a grade III recurrent distal radial lesion in the intralesional curettage group (3.57%) Ennekings functional score with intralesional curettage (25.41) was better than enbloc excision (21.37). Enbloc excision had higher rates of infections (36.84 % Vs 25%) and soft tissue coverage problems (21.05% Vs 0). Conclusion: Intralesional therapy has a better functional outcome and less complications than enbloc excision, albeit with a high recurrence rate which can however be effectively treated with repeat extended curettage.

Spectrum of Synovial Pathologies: A Pictorial Assay

The synovium, a specialized vascular tissue, lines the diarthrodial joints, bursae, and tendon sheaths of the body. It helps in nourishment of articular structures. The synovium is affected by a variety of disorders that can be either localized or systemic. Although normal synovium is barely perceptible on magnetic resonance imaging, it provides an excellent imaging modality for the evaluation of pathologic processes involving the synovium. The pathologic processes affecting the synovium include 1 of the following etiologies: inflammatory, infectious, degenerative, traumatic, or neoplastic and tumor-like conditions. In this article, we discuss the magnetic resonance imaging technique and the sequences used in the evaluation of synovial pathologies and review the characteristic imaging findings of specific conditions thus narrowing the differential diagnoses.