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

INTRODUCTION: We conducted a systematic review to determine the optimal treatment options in patients with desmoid tumours who have declined observational management. METHODS: A search was conducted of the medline and embase databases (1990 to September 2012), the Cochrane Library, and relevant guideline Web sites and conference materials. RESULTS: One 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. CONCLUSIONS: In 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.

Treatment and follow-up strategies in desmoid tumours: a practice guideline.

OBJECTIVES: We set out to determine the optimal treatment options-surgery, radiation therapy (rt), systemic therapy, or any combinations thereof-for patients with desmoid tumours once the decision to undergo active treatment has been made (that is, monitoring and observation have been determined to be inadequate).provide clinical-expert consensus opinions on follow-up strategies in patients with desmoid tumours after primary interventional management. METHODS: This guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care and the Sarcoma Disease Site Group. The medline, embase, and Cochrane Library databases, main guideline Web sites, and abstracts of relevant annual meetings (1990 to September 2012) were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Sarcoma Disease Site Group. RECOMMENDATIONS TREATMENTS: Surgery with or without rt can be a reasonable treatment option for patients with desmoid tumours whose surgical morbidity is deemed to be low.The decision about whether rt should be offered in conjunction with surgery should be made by clinicians and patients after weighing the potential benefit of improved local control against the potential harms and toxicity associated with rt.Depending on individual patient preferences, systemic therapy alone or rt alone might also be reasonable treatment options, regardless of whether the desmoid umours are deemed to be resectable. RECOMMENDATIONS FOLLOW-UP STRATEGIES: Undergo evaluation for rehabilitation (occupational therapy or physical therapy, or both).Continue with rehabilitation until maximal function is achieved.Undergo history and physical examinations with appropriate imaging every 3-6 months for 2-3 years, and then annually.

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

QUESTIONS: In 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? BACKGROUND: Surgery 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. METHODS: The 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. RESULTS AND CONCLUSIONS: Thirty-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.

The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study.

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H(2)O(2)) and 50% zinc chloride (ZnCI(2)) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions. Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H(2)O(2) and 50% ZnCI(2). The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures. These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone.

Cyclin D1 and p21 is elevated in the giant cells of giant cell tumors.

Alterations of cell cycle regulatory proteins, especially those that regulate G1 to S transition, have been implicated in the pathogenesis of a wide variety of human tumors. In previous studies we showed that that there is overexpression of cyclin D1 protein predominately in the giant cell component of giant cell tumors of bone. The purpose of this study was to investigate the mechanisms that may be responsible for cyclin D1 accumulation in giant cell tumors. Giant cell tumors have high levels of cyclin D1 mRNA and the giant cell-enriched population of these tumors have significantly more mRNA and protein expression of cyclin D1 than the mononuclear cell population. The giant cells also expressed higher levels of p21 protein and more p21 bound to cyclin D1 than the mononuclear cells. It is possible that p21 may be contributing to the cyclin D1 accumulation that occurs in the giant cells and perhaps even giant cell formation in these tumors. Additional studies are required to confirm the role of p21 in the pathogenesis of these tumors.

Arthroplasty with a metal radial head for unreconstructible fractures of the radial head.

BACKGROUND: Treatment of unreconstructible comminuted fractures of the radial head remains controversial. There is limited information on the outcome of management of these injuries with arthroplasty with a metal radial head implant. METHODS: The functional outcomes of arthroplasties with a metal radial head implant for the treatment of twenty-five displaced, unreconstructible fractures of the radial head in twenty-four consecutive patients (mean age, fifty-four years) were evaluated at a mean of thirty-nine months (minimum, two years). There were ten Mason type-III and fifteen Mason-Johnston type-IV injuries. Two of these injuries were isolated, and twenty-three were associated with other elbow fractures and/or ligamentous injuries. RESULTS: At the time of follow-up, Short Form-36 (SF-36) summary scores suggested that overall health-related quality of life was within the normal range (physical component = 47 +/- 10, and mental component = 49 +/- 13). Other outcome scales indicated mild disability of the upper extremity (Disabilities of the Arm, Shoulder and Hand score = 17 +/- 19), wrist (Patient-Rated Wrist Evaluation score = 17 +/- 21 and Wrist Outcome Score = 60 +/- 10), and elbow (Mayo Elbow Performance Index = 80 +/- 16). According to the Mayo Elbow Performance Index, three results were graded as poor; five, as fair; and seventeen, as good or excellent. The poor and fair outcomes were associated with concomitant injury in two patients, a history of a psychiatric disorder in three, comorbidity in two, a Workers' Compensation claim in two, and litigation in one. Subjective patient satisfaction averaged 9.2 on a scale of 1 to 10. Elbow flexion of the injured extremity averaged 140 degrees +/- 9 degrees; extension, -8 degrees +/- 7 degrees; pronation, 78 degrees +/- 9 degrees; and supination, 68 degrees +/- 10 degrees. A significant loss of elbow flexion and extension and of forearm supination occurred in the affected extremity, which also had significantly less strength of isometric forearm pronation (17%) and supination (18%) as well as significantly less grip strength (p < 0.05). Asymptomatic bone lucencies surrounded the stem of the implant in seventeen of the twenty-five elbows. Valgus stability was restored, and proximal radial migration did not occur. Complications, all of which resolved, included one complex regional pain syndrome, one ulnar neuropathy, one posterior interosseous nerve palsy, one episode of elbow stiffness, and one wound infection. CONCLUSIONS: Patients treated with a metal radial head implant for a severely comminuted radial head fracture will have mild-to-moderate impairment of the physical capability of the elbow and wrist. At the time of short-term follow-up, arthroplasty with a metal radial head implant was found to have been a safe and effective treatment option for patients with an unreconstructible radial head fracture; however, long-term follow-up is still needed.

Early fixation of the vertically unstable pelvis: the role of iliosacral screw fixation of the posterior lesion.

OBJECTIVES: To evaluate the effectiveness of the use of iliosacral screw fixation in the management of the vertically unstable pelvis. STUDY DESIGN: Retrospective analysis with clinical follow-up of patients to assess functional outcome. METHODS: Thirty-eight vertically unstable pelvic fractures were treated using iliosacral screw fixation. Anterior fixation was by means of plating in sixteen pelves and by external fixation in fifteen pelves. Four pelves had no anterior fixation. Complications were recorded and radiographs were analyzed to classify fractures and identify screw misplacement and malunion. Twenty-six patients had a functional evaluation. RESULTS: Five patients (13 percent) suffered a pulmonary embolus in the early postoperative period, one of which was fatal, a hospital mortality of 2.6 percent. Screw misplacement occurred in five patients but there were no adverse sequelae. In thirty-four cases with radiographic follow-up, malunion was noted in fifteen cases (44 percent). A lower rate of malunion (36 percent) was noted with internal fixation of the anterior lesion. Of twenty-six patients with long-term follow-up, only four (15 percent) had no pain. Sacroiliac fusion for pain was performed in three patients (11 percent). Twelve patients (46 percent) returned to their preinjury occupation, six patients (23 percent) changed occupation, and nine patients (30 percent) had not yet returned to work by last follow-up. CONCLUSIONS: Iliosacral screw fixation is a useful method of fixation in the vertically unstable pelvis but needs to be augmented by rigid anterior fixation to minimize malunion.

Three-dimensional CT measurement of adult acetabular dysplasia: technique, preliminary results in normal subjects, and potential applications.

OBJECTIVE: To assess a three-dimensional computed tomography (3DCT) technique for measurement of acetabular coverage in adults. DESIGN: We used 3DCT to define the geometric centre of the femoral head and to measure centre-edge angles (CEAs) at 10 degrees rotational increments around the acetabular rim. The means, ranges, standard deviations and 95% confidence intervals for the CEAs at the various rotational increments were determined. Inter- and intra-observer variability was measured. The normal values are compared with two example cases of acetabular dysplasia. PATIENTS: The normal hips of 15 subjects aged 1949 years (mean 34.2 years) were measured. RESULTS: The 3DCT measurements are reproducible (mean difference interobserver, 1.7 degrees - 7.9 degrees; mean difference intra-observer, 0.6 degrees-6.9 degrees). Mean normal CEA at the lateral rim was 33 degrees with a 95% confidence interval of 23 degrees - 43 degrees. Mean normal CEAs at 10 rotational increments from anterior to posterior rim were determined, and graphed as a 'normal curve'. CONCLUSION: This new 3DCT method of assessing acetabular dysplasia is simple, reproducible, and applicable to diagnosis, quantification and surgical planning for adult acetabular dysplasia patients.

Effect of low-molecular-weight heparin on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.

We employed a canine model of pulmonary embolism induced by radioactive blood clots to determine if low-molecular-weight heparin augments recombinant tissue plasminogen activator (rtPA)-induced thrombolysis. Following embolization, dogs were randomized: group 1 dogs received heparin; group 2 dogs received low-molecular-weight heparin; group 3 dogs received 1.5 mg/kg of rtPA over 45 minutes; group 4 dogs received rtPA 3 mg/kg over 45 minutes; and group 5 dogs received 1.5 mg/kg of rtPA plus low-molecular-weight heparin. Over three hours, little thrombolysis occurred in groups 1 and 2. In contrast, significant thrombolysis occurred in groups 3 to 5, 46 percent, 49 percent, and 46 percent, respectively (all p less than 0.01 compared with groups 1 and 2). We conclude that there is an upper limit to the dose-thrombolytic rate relationship with rtPA, and that low-molecular-weight heparin does not augment rtPA-induced thrombolysis.