Surgical treatment of femoroacetabular impingement: a systematic review of the literature.

UNLABELLED: The surgical treatment of femoroacetabular impingement has become more common, yet the strength of clinical evidence to support this surgery is debated. We performed a systematic review of the literature to (1) define the level of evidence regarding hip impingement surgery; (2) determine whether the surgery relieves pain and improves function; (3) identify the complications; and (4) identify modifiable causes of failure (conversion to total hip arthroplasty). We searched the literature between 1950 and 2009 for all studies reporting on surgical treatment of femoroacetabular impingement. Studies with clinical outcome data and minimum two year followup were analyzed. Eleven studies met our criteria for inclusion. Nine were Level IV and two were Level III. Mean followup was 3.2 years; range (2-5.2 years). Reduced pain and improvement in hip function were reported in all studies. Conversion to THA was reported in 0% to 26% of cases. Major complications occurred in 0% to 18% of the procedures. Current evidence regarding femoroacetabular impingement surgery is primarily Level IV and suggests the various surgical techniques are associated with pain relief and improved function in 68-96% of patients over short-term followup. Long-term followup is needed to determine survivorship and impact on osteoarthritis progression and natural history. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Combined periacetabular and femoral osteotomies for severe hip deformities.

Periacetabular osteotomy (PAO) is an effective acetabular reorientation technique for treatment of symptomatic acetabular dysplasia. In hips with severe deformities, an adjunctive femoral osteotomy (PFO) may optimize correction, joint stability, and congruency. We analyzed the clinical and radiographic results of combined PAO/PFO in treating severe hip deformities. Second, we compared the clinical results of patients treated with PAO/PFO with patients treated with isolated PAO for lesser deformities. Twenty-five patients (28 hips) treated with PAO/PFO were reviewed and followed a minimum of 16 months (mean, 44 months). The matched PAO cohort included 25 patients (28 hips). For the PAO/PFO group, the average Harris hip score improved from 60.9 to 86.3. Eighty-nine percent of the patients demonstrated at least a 10-point improvement in the hip score and 75% had a Harris hip score over 80 points. Radiographic evaluation demonstrated consistent deformity correction. The PAO/PFO group had a lower average Harris hip score preoperatively, yet hip function after surgery was comparable between groups. These data indicate combined PAO/PFO is associated with improved hip function in most patients. These clinical results are comparable to those obtained with isolated PAO for lesser hip deformities.

Periacetabular osteotomy: a systematic literature review.

UNLABELLED: The Bernese periacetabular osteotomy is commonly used to treat symptomatic acetabular dysplasia. Although periacetabular osteotomy is becoming a more common surgical intervention to relieve pain and improve function, the strength of clinical evidence to support this procedure for these goals is not well defined in the literature. We therefore performed a systematic review of the literature to define the level of evidence for periacetabular osteotomy, to determine deformity correction, clinical results, and to determine complications associated with the procedure. Thirteen studies met our inclusion criteria. Eleven studies were Level IV, one was Level III, and one was Level II. Radiographic deformity correction was consistent and improvement in hip function was noted in all studies. Most studies did not correlate radiographic and clinic outcomes. Clinical failures were commonly associated with moderate to severe preoperative osteoarthritis and conversion to THA was reported in 0% to 17% of cases. Major complications were noted in 6% to 37% of the procedures. These data indicate periacetabular osteotomy provides pain relief and improved hip function in most patients over short- to midterm followup. The current evidence is primarily Level IV. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

CCL2 is a potent regulator of prostate cancer cell migration and proliferation.

Tumor cells in the bone interact with the microenvironment to promote tumor cell survival and proliferation, resulting in a lethal phenotype for patients with advanced prostate cancer. Monocyte chemoattractant protein 1 (CCL2) is a member of the CC chemokine family and is known to promote monocyte chemotaxis to sites of inflammation. Here we have shown that human bone marrow endothelial (HBME) cells secrete significantly higher levels of CCL2 compared to human aortic endothelial cells and human dermal microvascular endothelial cells. Furthermore, we demonstrate that CCL2 is a potent chemoattractant of prostate cancer epithelial cells, and that stimulation of PC-3 and VCaP cells resulted in a dose-dependent activation of PI3 kinase/Akt signaling pathway. Activation of the PI3 kinase/Akt pathway was found to be vital to the proliferative effects of CCL2 stimulation of both PC-3 and VCaP cells. Additionally, CCL2 stimulated the phosphorylation of p70-S6 kinase (a downstream target of Akt) and induced actin rearrangement, resulting in a dynamic morphologic change indicative of microspike formation. These data suggest that bone marrow endothelial cells are a major source of CCL2, and that an elevated secretion of CCL2 recruits prostate cancer epithelial cells to the bone microenvironment and regulates their proliferation rate.

Development of the VCaP androgen-independent model of prostate cancer.

Prostate epithelial cell growth is dependent on the presence of androgens, and transition of prostate cancer to an androgen-independent phenotype results in a highly aggressive, currently incurable cancer. We have developed a new preclinical model of androgen-independent prostate cancer derived from the VCaP prostate cancer epithelial cell line. VCaP cells were subcutaneously implanted and serially passaged in castrated male severe combined immunodeficient mice. Androgen independence was confirmed by WST-1 (a tetrazolium salt) cell proliferation assay in the absence or presence of dihydrotesterone (1-100 nM). VCaP androgen-sensitive cells responded dose dependently to dihydrotesterone, whereas VCaP androgen-independent cells did not alter their proliferation in response to dihydrotesterone. Gene expression of androgen receptor, B-cell lymphoma-2, prostate cancer antigen 3, prostate acid phosphatase, 6 transmembrane epithelial antigen of the prostate, and survivin was determined by polymerase chain reaction amplification. B-cell lymphoma-2 expression was up regulated in the VCaP androgen-independent lines compared to the VCaP androgen-sensitive, suggesting a possible mechanism of androgen independence. Furthermore, tumor-associated angiogenesis was assessed by immunofluorescence confocal microscopy of CD31. VCaP androgen-independent tumors showed enhanced angiogenesis compared to VCaP androgen-sensitive tumors. These results illustrate the development of a novel model of prostate cancer androgen independence and provide a new system to study angiogenesis and the transition to androgen independence.

Differential expression analysis of MIM (MTSS1) splice variants and a functional role of MIM in prostate cancer cell biology.

We previously identified MIM-A (missing in metastasis, MTSS1) by differential display techniques as missing in invasive, metastatic bladder cancer cell lines and suggested that MIM-A is a novel putative metastasis suppressor gene. Characterization of the MIM gene revealed a WH2 (Wiskott-Aldrich syndrome protein homology 2) domain in the C-terminus that is known to bind actin monomers and regulate organization of the actin cytoskeleton. Here, we further describe two alternatively splice variants of MIM-A, called MIM(12del) and MIM-B, which share > 50% amino acid sequence homology with MIM-A in the C-terminal domain. We show that expression of all three transcripts is down-regulated in prostate cancer cell lines and tumor samples from patients. In addition, we generated stably-transfected PC-3 cells overexpressing MIM-A to evaluate the importance of MIM-A in prostate cancer biology. The initial experiments show that expression of MIM decreased the number of actin filaments and was associated with a decrease in the G:F actin ratio. Overexpression of MIM-A had no effect on PC-3 cell adhesion to extracellular matrices, as well as no effect on PC-3 motility. Further, overexpression of MIM-A reduced the rate of PC-3 cell proliferation. These results support the hypothesis that MIM-A is an actin-binding protein and implicate a role of MIM-A in the regulation of cellular proliferation. These data suggest that the reduction of MIM-A gene expression in prostate cancer and other cancers may contribute to tumor growth and development, as well as metastasis.