Robert H. Quinn

Phase IB study of the combination of docetaxel, gemcitabine, and bevacizumab in patients with advanced or recurrent soft tissue sarcoma: the Axtell regimen.

BACKGROUND To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated. PATIENTS AND METHODS Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m(2) was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m(2), bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m(2), every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry. RESULTS The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome. CONCLUSIONS The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.BACKGROUND To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated. PATIENTS AND METHODS Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m2 was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m2, bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m2, every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry. RESULTS The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome. CONCLUSIONS The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.

Tumors masquerading as hematomas.

Suboptimal patient management can occur when malignant soft tissue tumors with internal hemorrhage masquerade as simple hematomas. We retrospectively reviewed 31 patients with malignancies who had diagnostic delays averaging 6.7 months (range, 1.0-49.3 months). The diagnoses included soft tissue sarcomas (27), metastatic cancers (three), and lymphoma (one). History of subcutaneous ecchymosis was positive in only five patients (three of whom had trauma), negative in 18, and unknown in eight. Ecchymosis was present in two patients, absent in 20, and unknown in nine. Previous treatments included observation and reassurance (21), aspiration (11), incision and drainage (10), unplanned resections (seven), physical therapy (seven), medication administration (six), and arthroscopy (one). Interpretations of initial MRI (21) and ultrasound (four) did not raise suspicion of underlying cancers. Traumatic hemorrhage usually causes subcutaneous ecchymosis. However, intratumoral hemorrhage often is contained by a pseudocapsule, which prevents fascial plane tracking and subcutaneous ecchymosis, thus providing a diagnostic clue. Magnetic resonance imaging and ultrasound studies may not accurately diagnose questionable lesions. Diagnostic delay or inappropriate treatment may result if patients do not receive appropriate followup, biopsy (usually open), or referral whenever the diagnosis is in doubt.Level of Evidence: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

The effect of time delay to surgical debridement of open tibia shaft fractures on infection rate.

Historical practices have advocated emergent operative debridement for all open fractures. To date only studies in guinea pigs have demonstrated decreased infection with surgical intervention within 6 hours of injury. Recent studies have questioned this practice in humans. The purpose of this study was to determine if there was an increased infection rate based on time delay from presentation to initial operative debridement. A retrospective chart review was done from 1998 to 2004 to identify patients who presented to our level 1 trauma center with open tibia shaft fractures and had at least 2 years of follow-up. Two hundred fifteen open tibia shaft fractures in 206 patients were included in this study. A time delay of 0 to 6 hours revealed a 10.8% (7/65) infection rate, of 6 to 12 hours a 9.5% (9/95) infection rate, of 12 to 24 hours a 5.6% (2/36) infection rate, and no infections in a delay >24 hours (N=19). Using the Mantel-Haenszel chi-square test, P=.12; Fisher exact test P value was .53. Combining time intervals to 0 to 12 hours and >12 hours returned 10% (16/160) and 3.6% (2/55) infection rates, respectively. Fisher exact test P value was .17. Statistical analysis failed to show significant differences among the various time interval groups. Based on current evidence, we recommend that in the absence of gross contamination, early informal irrigation should be done on an urgent basis along with initiation of intravenous antibiotics, while a formal debridement combined with fixation, if indicated, can be done later in a timely manner.

Contemporary Management of Metastatic Bone Disease: Tips and Tools of the Trade for General Practitioners

Metastatic bone disease has a substantial impact on mortality and health-related quality of life. The aging of the population in the United States and the improved survival rate of patients with cancer have led to an increase in the prevalence of osseous metastatic lesions that are symptomatic and may require orthopaedic care. Skeletal related events in neoplastic disease include pain, pathologic fracture, hypercalcemia, and neural compression including spinal cord compression. Approximately 400,000 patients develop metastatic bone disease in the United States annually, and bone is the fourth most common metastatic site, after the lymphatic system, lung, and liver1-3. Seventy percent of patients with metastatic breast or prostate cancer compared with 20% to 30% of patients with metastatic lung or gastrointestinal cancers develop bone metastases2. Breast cancer patients experience a mean of 2.2 to 4.0 skeletal events annually, while prostate cancer patients experience a mean of 1.5 skeletal events3. The general orthopaedic practitioner is the primary evaluator and treating physician for an increasing population of patients with skeletal events. The purpose of this paper is to review contemporary strategies for the management of metastatic bone disease. Prognosis in metastatic bone disease is determined by the primary tumor and cell type. Table I illustrates some of these differences as well as current survival estimates4,5. Figures 1-A and 1-B show a pathologic fracture related to metastatic breast carcinoma that healed following internal fixation and radiation. An accurate diagnosis and staging of metastatic bone disease are fundamental to guiding an evidence-based approach to management. View this table: TABLE I Tumor Characteristics A patient with metastatic breast carcinoma who developed a pathologic fracture of the humerus. Fig. 1-A Preoperative anteroposterior radiograph of the humerus demonstrating the pathologic fracture. Fig. 1-B Radiograph made after internal fixation and radiation therapy showing healing of the fracture. The clinical evaluation and diagnostic studies of the patient who presents with a …

Preliminary traction in the treatment of developmental dislocation of the hip.

The benefit of preliminary traction in the treatment of developmental dislocation of the hip has not been clearly demonstrated. We retrospectively analyzed the results of traction treatment of 90 dislocated hips in 72 patients. After a 3-week course of traction, patients underwent attempted closed reduction. Fifty-two hips (58%) were managed successfully by closed reduction, whereas 38 hips (42%) required primary open reduction, x2 analysis revealed no significant difference in either the rate of successful closed reduction or the incidence of avascular necrosis compared to recently published series in which preliminary traction was not used. On the basis of presentation radiographs and arthrograms, we were unable to identify a subgroup of patients that clearly benefited from the use of traction in the treatment of developmental dislocation of the hip.

The management of open fractures

Abstract This is a review of Medline and PubMed articles on open fractures published in the English literature between 1945 and April 2005. The emphasis of most published articles has been placed on definitive treatment of these injuries at sophisticated referral hospitals. The prehospital emphasis has been on rapid evacuation and referral to ensure that definitive treatment can be initiated as quickly as possible. Little has been discussed about the management of these injuries in remote settings where evacuation may consume considerably more time. Contemporary recommendations for management of these injuries are reviewed.

Wilderness Medical Society Practice Guidelines for Spine Immobilization in the Austere Environment

In an effort to produce best-practice guidelines for spine immobilization in the austere environment, the Wilderness Medical Society convened an expert panel charged with the development of evidence-based guidelines for management of the injured or potentially injured spine in an austere (dangerous or compromised) environment. Recommendations are made regarding several factors related to spinal immobilization. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks or burdens for each factor according to the methodology stipulated by the American College of Chest Physicians. A treatment algorithm based on the guidelines is presented.

Wilderness Medical Society Practice Guidelines for Spine Immobilization in the Austere Environment: 2014 Update

In an effort to produce best practice guidelines for spine immobilization in the austere environment, the Wilderness Medical Society convened an expert panel charged with the development of evidence-based guidelines for management of the injured or potentially injured spine in an austere (dangerous or compromised) environment. Recommendations are made regarding several parameters related to spinal immobilization. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians. A treatment algorithm based on the guidelines is presented. This is an updated version of original WMS Practice Guidelines for Spine Immobilization in the Austere Environment published in Wilderness & Environmental Medicine 2013;24(3):241-252.

Wilderness medical society practice guidelines for basic wound management in the austere environment: 2014 update

In an effort to produce best-practice guidelines for wound management in the austere environment, the Wilderness Medical Society convened an expert panel charged with the development of evidence-based guidelines for the management of wounds sustained in an austere (dangerous or compromised) environment. Recommendations are made about several parameters related to wound management. These recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks or burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians. This is an updated version of the original guidelines published in Wilderness & Environmental Medicine 2014;25(3):295-310.

Wilderness Medical Society Practice Guidelines for Basic Wound Management in the Austere Environment

In an effort to produce best-practice guidelines for wound management in the austere environment, the Wilderness Medical Society convened an expert panel charged with the development of evidence-based guidelines for the management of wounds sustained in an austere (dangerous or compromised) environment. Recommendations are made about several parameters related to wound management. These recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks or burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians.