Michelle Ghert

A Systematic Review and Meta-Analysis of Oncologic Outcomes of Pre- Versus Postoperative Radiation in Localized Resectable Soft-Tissue Sarcoma

BackgroundThe goal of this study was to determine the oncologic outcomes in localized resectable soft-tissue sarcoma after pre- versus postoperative radiation.MethodsLiterature searches through MEDLINE, EMBASE, CancerLit, and the Cochrane Database were performed with the following search terms: sarcoma, radiation, preoperative, and postoperative. Two reviewers independently assessed all eligible publications with the Detsky Quality Scale for Randomized Trials and the Newcastle-Ottawa Quality Assessment Scale for case–control studies. The primary outcome measure was the pooled odds ratio and 95% confidence intervals (95% CI) for the risk of local recurrence calculated through the fixed- and random-effects methods. Time-dependent survival data were calculated as an average across all studies.ResultsFive eligible studies were identified including a total of 1,098 patients. The P value for heterogeneity was 0.259, and the variability (I2) in results across studies due to true differences in treatment effect was 25%. The risk for local recurrence was lower in the preoperative group with an odds ratio of 0.61 (95% CI 0.42–0.89) by means of the fixed-effects method, and an odds ratio of 0.67 (95% CI 0.39–1.15) by means of the random-effects method. Average survival was 76% (range 62–88%) in the preoperative group and 67% (range 41–83%) in the post-operative group.ConclusionsThe delay in surgical resection necessary to complete preoperative radiation does not seem to increase the risk of lethal metastatic spread. The risk of local recurrence may be lower after preoperative radiation. These findings must be interpreted with caution because of the heterogeneity and bias in the available studies.

Myxoid\Round Cell Liposarcoma (MRCLS) Revisited: An Analysis of 418 Primarily Managed Cases

BackgroundObjectives of this study were to evaluate oncologic outcomes and to provide guidelines for the management of primary myxoid (MLS) and round cell liposarcoma (RCLS).MethodsA multicenter, retrospective study of 418 cases of MRCLS primarily managed by Canadian multidisciplinary sarcoma teams.ResultsStudy included 418 cases (MLS: 311 patients and RCLS: 107;xa0>xa05% round cell) with a median age of 45xa0years and a median follow-up of 5.2xa0years. Median tumor size was 10xa0cm, and 81% were deep and 90% were in lower limb. The majority of patients underwent surgical resection and radiotherapy, with a small percentage (6%) receiving chemotherapy. The overall 10-year local control rate was 93% with no differences between MLS and RCLS. Radiotherapy was significant in preventing local relapse and reducing tumor diameter (medianxa0=xa018%) and improving microscopic margin status, but did not impact survival. Radiotherapy and the margin status were independent predictors of local recurrence. The 5- and 10-year metastatic-free survivals were 84 and 77% respectively for MLS and 69 and 46% for RCLS. The initial site of metastasis was found in multiple locations (34%) and bone involvement was frequent (40%) with predilection for spine (79%). Round cell percent (>xa05%) and tumor diameter (>xa010xa0cm) correlated with increased risk for metastasis and death.ConclusionsMLS and RCLS showed different metastatic risk but equally good local control. Radiotherapy was effective in preventing local recurrence and should be delivered as neoadjuvant. New staging strategies are to be defined to account for the unusual metastatic pattern.

High-Speed Burring with and without the Use of Surgical Adjuvants in the Intralesional Management of Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis.

Local control rates for Giant Cell Tumor of Bone (GCT) have been reported in a large number of retrospective series. However, there remains a lack of consensus with respect to the need for a surgical adjuvant when intralesional curettage is performed. We have systematically reviewed the literature and identified six studies in which two groups from the same patient cohort were treated with intralesional curettage and high-speed burring with or without a chemical or thermal adjuvant. Studies were evaluated for quality and pooled data was analyzed using the fixed effects model. Data from 387 patients did not indicate improved local control with the use of surgical adjuvants. Given the available data, we conclude that surgical adjuvants are not required when meticulous tumor removal is performed.

Surgical margins and handling of soft-tissue sarcoma in extremities: a clinical practice guideline.

QUESTIONSnIn limb salvage surgery for extremity soft-tissue sarcoma (sts), what is an adequate surgical margin?What is the appropriate number of samples to take from the margins of a surgical resection specimen?What is the appropriate handling of surgical resection specimens?nnnBACKGROUNDnSurgery is the primary treatment for extremity sts. The combination of radiotherapy with surgery allows for limb salvage by using radiation to biologically sterilize microscopic extensions of tumour and to spare neurovascular and osseous structures. Adjuvant chemotherapy in sts-except for rhabdomyosarcoma and Ewing sarcoma-continues to be controversial.nnnMETHODSnThe medline and embase databases (1975 to June 2011) and the Cochrane Library were searched for pertinent studies. The Web sites of the main guideline organizations and the American Society of Clinical Oncology conference proceedings (2007-2010) were also searched.nnnRESULTS AND CONCLUSIONSnThirty-three papers, including four guidelines, one protocol, and one abstract, were eligible for inclusion. The data suggest that patients with clear margins have a better prognosis, but no prospective studies have indicated how wide margins should be. In limb-salvage surgery for extremity sts, the procedure should be planned to achieve a clear margin. However, to preserve functionality, surgery may result in a very close (<1 cm) or even microscopically positive margin. In this circumstance, the use of preoperative or postoperative radiation should be considered. No studies described the optimal number of tissue sections required to assess adequacy of excision nor the appropriate handling of surgical resection specimens. The Sarcoma Disease Site Group made its recommendations based on expert opinion and consensus.

Collagenase expression and activity in the stromal cells from giant cell tumour of bone

The characteristic bone destruction in giant cell tumour of bone (GCT) is largely attributed to the osteoclast-like giant cells. However, experimental analyses of bone resorption by cells from GCT often fail to exclude the neoplastic spindle-like stromal cells, and several studies have demonstrated that bone resorption by GCT cells is increased in the presence of stromal cells. The spindle-like stromal cells from GCT may therefore actively contribute to the bone resorption observed in the tumour. Type I collagen, a major organic constituent of bone, is effectively degraded by three matrix metalloproteinases (MMPs) known as the collagenases: MMP-1, MMP-8 and MMP-13. We established primary cell cultures from nine patients with GCT and the stromal cell populations were isolated in culture. The production of collagenases by primary cultures of GCT stromal cells was determined through real-time PCR, western blot analysis and a multiplex assay system. Results show that the cells produce MMP-1 and MMP-13 but not MMP-8. Immunohistochemistry confirmed the presence of MMP-1 and MMP-13 in paraffin-embedded GCT tissue samples. Medium conditioned by the stromal cell cultures was capable of proteolytic activity as determined by MMP-1 and MMP-13-specific standardized enzyme activity assays. The spindle-like stromal cells from GCT may therefore actively participate in the bone destruction that is characteristic of the tumour.

Arthroscopic surgery for synovial chondromatosis of the hip: a systematic review of rates and predisposing factors for recurrence.

PURPOSEnSynovial chondromatosis of the hip is a benign condition whereby pain and functional limitations occur due to numerous intra-articular osteochondral fragments produced by a metaplastic synovium. Recurrence not only worsens morbidity but may lead to malignant transformation. With reported recurrence rates as high as 22% by open surgical approaches and given the increasing use of hip arthroscopy for the treatment of synovial chondromatosis, we sought to quantify the recurrence rate after arthroscopy, as well as identify predisposing factors for recurrence.nnnMETHODSnUsing predetermined inclusion criteria, 3 electronic databases--Embase, Medline, and PubMed-were searched for relevant articles addressing arthroscopic surgery for synovial chondromatosis of the hip across all available dates up to and including February 16, 2014. A hand search of the reference sections of the included studies was also completed. Article screening was conducted in duplicate. Reviewer agreement statistics and descriptive statistics of the included studies are presented.nnnRESULTSnFrom an initial retrieval of 2,542 studies, 14 studies satisfied the criteria for inclusion. A total of 197 patients (age range, 13 to 81 years) underwent hip arthroscopy for removal of intra-articular osteochondral fragments and synovectomy to alleviate both mechanical symptoms and pain. Follow-up periods ranged from 1 to 184 months, with approximately 7.6% of patients (15 of 197) lost to follow-up. The recurrence rate after hip arthroscopy was 7.1% (14 of 197), and the rate of minor complications, such as perineal and pedal neurapraxia, was 1%.nnnCONCLUSIONSnFor synovial chondromatosis of the hip, arthroscopic removal of osteochondral fragments with synovectomy is both safe and effective, with a mean recurrence rate of 7.1%.nnnLEVEL OF EVIDENCEnLevel IV, systematic review of Level IV studies.

A systematic review of optimal treatment strategies for localized Ewing's sarcoma of bone after neo-adjuvant chemotherapy

OBJECTIVEnTo perform a systematic review to investigate the optimal treatment strategy among the options of surgery alone, radiotherapy (RT) alone, and the combination of RT plus surgery in the management of localized Ewings sarcoma of bone following neo-adjuvant chemotherapy.nnnMETHODSnMEDLINE and EMBASE (1999 to February 2015), the Cochrane Library, and relevant conferences were searched.nnnRESULTSnTwo systematic reviews and eight full texts met the pre-planned study selection criteria. When RT was compared with surgery, a meta-analysis combining two papers showed that surgery resulted in a higher event-free survival (EFS) than RT in any location (HR = 1.50, 95% CI 1.12-2.00; p = 0.007). However another paper did not find a statistically significant difference in patients with pelvic disease, and no papers identified a significant difference in overall survival. When surgery plus RT was compared with surgery alone, a meta-analysis did not demonstrate a statistically significant difference for EFS between the two groups (HR = 1.21, 95% CI 0.90-1.63). Both surgical morbidities and radiation toxicities were reported.nnnCONCLUSIONSnThe existing evidence is based on very low aggregate quality as assessed by the GRADE approach. In patients with localized Ewings sarcoma, either surgery alone (if complete surgical excision with clear margin can be achieved) or RT alone may be a reasonable treatment option. The optimal local treatment for an individual patient should be decided through consideration of patient characteristics, the potential benefit and harm of the treatment options, and patient preference.

A systematic review of active treatment options in patients with desmoid tumours

INTRODUCTIONnWe conducted a systematic review to determine the optimal treatment options in patients with desmoid tumours who have declined observational management.nnnMETHODSnA search was conducted of the medline and embase databases (1990 to September 2012), the Cochrane Library, and relevant guideline Web sites and conference materials.nnnRESULTSnOne systematic review and forty-six studies met the preplanned study selection criteria; data from twenty-eight articles were extracted and analyzed. For local control, three studies reported a statistically significant difference in favour of surgery plus radiotherapy (rt) compared with surgery alone, and one study did not; two studies reported the lack of a statistical difference between surgery plus rt and rt alone in maintaining local control. Multivariate risk factors for local recurrence included positive surgical margins and young patient age. Single-agent imatinib led to a progression-free survival rate of 55% at 2 years and 58% at 3 years. Methotrexate plus vinblastine led to a progression-free survival rate of 67% at 10 years. Significant toxicities were reported for all treatment modalities, including surgical morbidity, and rt- and chemotherapy-related toxicities.nnnCONCLUSIONSnIn patients who have declined observational management, the local control rate was higher with surgery plus rt than with surgery alone. However, the additional rt-related complications should be considered in treatment decision-making. Surgery, rt, and systemic therapy are all reasonable treatment options for patients with desmoid tumours.

Postoperative antibiotic prophylaxis in total hip and knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials

BACKGROUNDnPostoperative antibiotic prophylaxis is currently the standard of care for patients undergoing total hip and knee arthroplasty. We evaluated the evidence for this practice in the reduction of surgical-site infections.nnnMETHODSnWe systematically searched MEDLINE, Embase and the Cochrane Library for randomized controlled trials (RCTs) published up to Aug. 15, 2014. We included all RCTs that compared postoperative antibiotic prophylaxis with postoperative placebo or no treatment in patients undergoing primary total hip or knee arthroplasty for osteoarthritis. We combined outcomes for surgical-site infection using a random-effects model and quantified heterogeneity using the χ2 test and the I2 statistic. We assessed the overall quality of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.nnnRESULTSnWe identified 4 RCTs (n = 4036) that met the inclusion criteria. Surgical-site infections occurred in 3.1% (63/2055) of patients in the prophylaxis group and 2.3% (45/1981) in the control group. Postoperative prophylaxis did not reduce the rate of surgical-site infections compared with placebo (risk difference 0.01, 95% confidence interval 0.00 to 0.02; I2 = 26%). This result was robust to sensitivity testing for losses to follow-up. According to the GRADE approach, the overall quality of evidence was very low.nnnINTERPRETATIONnThe available evidence did not show efficacy of postoperative antibiotic prophylaxis for the prevention of surgical-site infections in patients undergoing total hip or knee arthroplasty. Multicentred RCTs are likely to have an important impact on the confidence in the effect estimate and to change the estimate itself.

Intra-articular nodular fasciitis of the shoulder: a case report and review of the literature

Nodular fasciitis is a benign proliferation of myofibroblasts usually arising adjacent to the fascia. In this report, we describe a rare case in which nodular fasciitis occurred in an intra-articular location in the shoulder of a 26-year-old man. The mass developed in the subscapularis recess of the shoulder and histological evaluation showed a myofibroblastic proliferation. MRI findings of intra-articular nodular fasciitis are discussed along with a review of previous reports.