Capsular thinning on magnetic resonance arthrography is associated with intra-operative hip joint laxity in women.

Hip microinstability is a recognized cause of hip pain in young patients. Intra-operative evaluation is used to confirm the diagnosis, but limited data exist associating magnetic resonance arthrography (MRA) findings with hip microinstability. To determine if a difference exists in the thickness of the anterior joint capsule and/or the width of the anterior joint recess on MRA in hip arthroscopy patients with and without an intra-operative diagnosis of hip laxity. Sixty-two hip arthroscopy patients were included in the study. Two musculoskeletal radiologists blinded to surgical results reviewed the MRAs for two previously described findings: (i) anterior joint capsule thinning; (ii) widening of the anterior joint recess distal to the zona orbicularis. Operative reports were reviewed for the diagnosis of joint laxity. In all patients with and without intra-operative laxity, there were no significant differences with either MRA measurement. However, twenty-six of 27 patients with intra-operative laxity were women compared with 11 of 35 patients without laxity (P < 0.001). In subgroup analysis of women, the intra-operative laxity group had a higher rate of capsular thinning compared with the non-laxity group (85% versus 45%; P = 0.01). A 82% of women with capsular thinning also had intra-operative laxity, compared with 40% without capsular thinning (P = 0.01). There were no differences regarding the width of the anterior joint recess. In this study, there was an association between capsular thinning and intra-operative laxity in female patients. Measuring anterior capsule thickness on a pre-operative MRA may be useful for the diagnosis of hip microinstability.

The Cliff Sign: A New Radiographic Sign of Hip Instability.

BACKGROUND: The preoperative diagnosis of hip microinstability is challenging. Although physical examination maneuvers and magnetic resonance imaging findings associated with microinstability have been described, there are limited reports of radiographic features. In patients with microinstability, we observed a high incidence of a steep drop-off on the lateral edge of the femoral head, which we have named the "cliff sign." PURPOSE: (1) To determine the relationship of the cliff sign and associated measurements with intraoperative microinstability and (2) to determine the interobserver reliability of these measurements. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: A total of 115 consecutive patients who underwent hip arthroscopy were identified. Patients with prior hip surgery, Legg-Calve-Perthes disease, fractures, pigmented villonodular synovitis, or synovial chondromatosis were excluded, resulting in the inclusion of 96 patients in the study. A perfect circle around the femoral head was created on anteroposterior pelvis radiographs. If the lateral femoral head did not completely fill the perfect circle, it was considered a positive cliff sign. Five additional measurements relating to the cliff sign were calculated. The diagnosis of microinstability was made intraoperatively by the (1) amount of traction required to distract the hip, (2) lack of hip reduction after initial traction release following joint venting, or (3) intraoperative findings consistent with hip microinstability. Continuous variables were analyzed through use of unpaired t tests and discrete variables with Fisher exact tests. Interobserver reliability (n = 3) was determined for each measurement. RESULTS: Overall, 89% (39/44) of patients with microinstability had a cliff sign, compared with 27% of patients (14/52) without instability (P < .0001). Conversely, 74% of patients with a cliff sign had microinstability, while only 12% of patients without a cliff sign had instability (P < .0001). In women younger than 32 years with a cliff sign, 100% (20/20) were diagnosed with instability. No differences were found in any of the 5 additional measurements. Excellent interobserver reliability was found for the presence of a cliff sign and the cliff angle measurement. CONCLUSION: We have identified a radiographic finding, the cliff sign, that is associated with the intraoperative diagnosis of hip microinstability and has excellent interobserver reliability. Results showed that 100% of young women with a cliff sign had intraoperative microinstability. The cliff sign may be useful in the preoperative diagnosis of hip microinstability.

Open treatment of dysplasia-other than PAO: does it have to be a PAO?

Hip dysplasia is a developmental disorder that results in anatomic abnormalities in which the acetabular coverage is insufficient. In the absence of severe degenerative changes, younger active patients with these symptomatic structural abnormalities are increasingly managed with joint-preserving operations. Historically there have been numerous reconstructive pelvic osteotomies. In recent years, the Bernese periacetabular osteotomy (PAO) has become the preferred osteotomy by many surgeons. Even so, as our understanding of the hip advances and new diagnostic and treatment techniques are developed, we sought to put a focus on the long-term results of augmental osteotomies and pelvic osteotomies other than the PAO, to see if any of these surgeries still have a place in the current algorithm of treatment for the dysplastic hip. As the longevity of the treatment is the focal point for joint preservation surgeries for the dysplastic hip, these authors have searched databases for articles in the English literature that reported results of long-term follow-up with a minimum of 11-year survivorship after surgical treatment of developmental dysplasia of the hip. Reconstruction osteotomies for the dysplastic hip are intended to restore normal hip anatomy and biomechanics, improve symptoms and prevent degenerative changes, in this manuscript each procedure is independently assessed on the ability to achieve these important characteristics.

Arthroscopic Hip Surgery in the Elite Athlete: Comparison of Female and Male Competitive Athletes.

BACKGROUND: Few studies have published the results of hip arthroscopic surgery in elite athletes and none studying a significant number of elite female athletes. PURPOSE: (1) To compare sex-based differences in the ability to return to prior competitive sports activity after arthroscopic hip surgery. (2) To compare sex-based differences in the type of sports activity, diagnosis, and treatment in athletes requiring hip arthroscopic surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data on all elite athletes who underwent primary hip arthroscopic surgery between 2007 and 2014 were included. Athletes with a Hip Sports Activity Scale (HSAS) score of over 6 were identified. The preoperative evaluation included a medical history, history of sports activity, and hip-specific outcome scores (Modified Harris Hip Score [MHHS] and International Hip Outcome Tool-33 [iHOT-33]). Surgical findings and time to return to competitive sports were documented. RESULTS: Of 547 hips in 484 consecutive patients, 98 elite athletes (49 female) with a mean follow-up of 18.9 ± 12.8 months were identified. Eighty patients desired to return to their original competitive activity: 38 were female (42 hips; mean age, 21.5 ± 3.9 years), and 42 were male (54 hips; mean age, 20.5 ± 1.9 years). Moreover, 84.2% of female athletes and 83.3% of male athletes were able to return to the same level of competition at a mean of 8.3 ± 3.0 and 8.8 ± 2.9 months, respectively. Significant improvements between preoperative and postoperative outcome scores were seen in both groups (all P < .0001). Female athletes had more pincer femoroacetabular impingement (FAI) ( P = .0004) and instability ( P < .0001). Conversely, male athletes were diagnosed more commonly with combined FAI ( P < .0001), demonstrated greater acetabular cartilage damage ( P = .0004), and required microfracture more often ( P = .0014). Female athletes competed more frequently in flexibility (4/38, 11%; P = .047) and endurance (9/38, 24%) sports, while male athletes participated in cutting (14/42, 33%), contact (6/42, 14%), and asymmetric (13/42, 31%) sports more often. Patients who returned to their baseline level of competition had a shorter duration of symptoms preoperatively ( P = .001). Microfracture status did not affect the ability to return to sports. CONCLUSION: Female and male elite athletes were able to return to competitive sports activity at the same or higher level after hip arthroscopic surgery at a similar rate, although their performance in sports was not measured. Distinct differences in the diagnosis, treatment, and type of sports activity between sexes were seen. The duration of symptoms negatively correlated with outcomes. Microfracture did not affect the return to sports.

Is there a distinct pattern to the acetabular labrum and articular cartilage damage in the non-dysplastic hip with instability?

PURPOSE: The purpose of this study was to determine whether or not there is a distinct pattern of injury to the acetabular labrum and/or cartilage in the hip with instability without bony dysplasia. METHODS: Surgical records and intra-operative images of consecutive patients who underwent primary hip arthroscopy for femoroacetabular impingement (FAI) and/or hip instability by the senior author from April 2007 to December 2014 were retrospectively reviewed. Pathological changes were documented and charted on a novel diagram of the acetabulum, and classified into eight patterns corresponding to the lesion's location and size. In patients who had acetabular chondroplasty treatment, the width of the cartilage lesion was recorded. RESULTS: A total of 953 hips in 886 patients were included, and patients who met our inclusion/exclusion criterion were grouped into an Instability-Only group (45 hips), an Instability-Dysplasia group (12 hips), as well as Pincer-FAI, Cam-FAI, and Combined-FAI groups consisting of 100, 54, and 269 hips, respectively. In the Instability-Only group, 42.2 % of the chondral and labral lesions demonstrated a "Straight-Anterior" pattern, which proportion was statistically significantly different compared with Pincer-FAI (p < 0.000), Cam-FAI (p = 0.0002), and Combined-FAI (p < 0.000) groups. In Instability-Only patients, only 15.6 % of the lesions had an "Anterior to Lateral" pattern, a significantly lower proportion (p < 0.000) compared with the FAI groups. Also 11.1 % of the lesions demonstrated a "Lateral" pattern, which is a significantly greater proportion compared with Pincer-FAI (p < 0.000) and Combined-FAI (p < 0.000) groups. The mean width of the cartilage lesions for the Instability-Only group was 2.9 mm, which was significantly shallower than for the other FAI groups (p < 0.000). CONCLUSION: A significant predilection of "Straight-Anterior" or "Lateral" location of labral and/or cartilage damage was observed in the hip with instability, while there was shallow width of articular cartilage damage in these patients. These results suggest that there is a distinctive labral and cartilage damage pattern for hips with instability without inherent bony dysplasia. LEVEL OF EVIDENCE: Diagnostic study, Level IV.

Expression of vascular cell adhesion molecule-1 indicates the differentiation potential of human bone marrow stromal cells.

Bone marrow stromal cells (BMSCs) are a mixture of cells differing in differentiation potential including mesenchymal stem cells, and so far no CD antigens were found to be predictable for the differentiation property of each BMSC. Here we attempted to isolate differentiation-associated CD antigens using 100 immortalized human BMSC (ihBMSC) clones. Among 13 CD antigens analyzed, only CD106/Vascular cell adhesion molecule-1 (VCAM-1) showed a clear correlation with the differentiation potential of each clone; CD106-positive ihBMSC clones were less osteogenic and more adipogenic than CD106-negative clones. This association was confirmed in primary BMSCs sorted by CD106, showing that the CD106-positive fraction contained less osteogenic and more adipogenic cells than the CD106-positive fraction. The evaluation of CD106 fraction of BMSC strains in early passages predicted clearly the osteogenic and adipogenic potential after in vitro induction of differentiation, indicating the usefulness of CD106 as a differentiation-predicting marker of BMSC.

Expression of the p16INK4A gene is associated closely with senescence of human mesenchymal stem cells and is potentially silenced by DNA methylation during in vitro expansion.

The precise biological characteristics of human mesenchymal stem cells (hMSCs), including growth regulatory mechanisms, have not yet been defined. Using 29 strains of hMSCs isolated from bone marrow, we have performed extensive analyses of the growth profiles of hMSCs in vitro. All 29 strains stopped proliferating with a mean population doubling (PD) of 28, although there was a considerable difference among strains. The mean telomere restriction fragment length of the cells passaged twice correlated well with the final number of PDs in each strain, suggesting the value of this measurement to be predictive of the growth potential of hMSCs. The expression level of the p16INK4A gene was associated closely with the PD number of each strain (p = .00000001). Most of the p16INK4A-positive cells were Ki67-negative and senescence associated beta-galactosidase-positive, and the suppression of p16INK4A gene expression by small interfering RNA in senescent hMSCs reduced the number of senescent cells and endowed them with the ability to proliferate. Twenty-five of the 29 strains showed a steady gradual increase in the expression of p16INK4A. The remaining four strains (13.8%) showed different profiles, in which DNA methylation in the promoter region occurred in vitro. One of the four strains continued to proliferate for much longer than the others and showed chromosomal aberrations in the later stages. These results indicated p16INK4A to be a key factor in the regulation of hMSC growth, and, most importantly, careful monitoring of DNA methylation should be considered during the culture of hMSCs, particularly when a prolonged and extended propagation is required.

In vitro transformation of mesenchymal stem cells by oncogenic H-rasVal12.

Tissue stem cells may serve as progenitors for malignant tumors derived from the same tissue. Here, we report the establishment of immortalized human mesenchymal stem cells (ihMSC) and tested the feasibility of using ihMSC as presarcomatous cells. Immortalization was achieved by introducing the genes for human telomerase reverse transcriptase and Bmi1. ihMSC retained the potential for multi-directional differentiation of the original MSC. To transform ihMSC, we introduced an oncogenic H-ras(Val12) gene, and established the cell line ihMSC-ras. ihMSC-ras had the phenotype of fully transformed cells and retained adipogenic and chondrogenic, but not osteogenic, potential. Interestingly, ihMSC-ras demonstrated morphological features of autophagy, and inhibition of the ERK pathway suppressed the production of autophagosomes, indicating that ras/ERK signaling is responsible for the induction of autophagy. Thus ihMSC will serve as a material with which to analyze the tumorigenic and differentiation-modifying effects of candidate oncogenes involved in the development of sarcomas.

Expression of claudin7 is tightly associated with epithelial structures in synovial sarcomas and regulated by an Ets family transcription factor, ELF3.

Synovial sarcoma, a soft tissue sarcoma that develops in adults, is pathologically subclassified into monophasic spindle synovial sarcoma and biphasic synovial sarcoma with epithelial components. The molecular mechanism building the epithelial components in biphasic synovial sarcoma is totally unknown. Here we investigated claudins, critical molecules in the tight junction, in biphasic synovial sarcoma. Expression profiles of 21 claudins in 17 synovial sarcoma tumor samples, including 9 biphasic tumors, identified claudin4, claudin7, and claudin10 as biphasic tumor-related claudins, and immunohistochemical analyses demonstrated the localization of these claudins in the epithelial component in biphasic tumors, with claudin7 the most closely associated with the epithelial component. The mRNA expression and protein localization of claudin7 coincided with those of the ELF3, an epithelia-specific member of the Ets family of transcription factors. Luciferase reporter assays demonstrated that the presence of the Ets-binding site at -150 in the promoter region of the claudin7 gene was critical for the transcriptional activity, and gel shift and chromatin immunoprecipitation assays confirmed the binding of ELF3 to the Ets site at -150. Inhibition of ELF3 expression by small interfering RNA simultaneously down-regulated the mRNA expression of the claudin7 gene, and the introduction of ELF3 expression in claudin7-negative cell lines induced mRNA expression of the claudin7 gene. Therefore, the induction of claudin7 expression by ELF3 appears critical to the formation of the epithelial structures in biphasic synovial sarcoma.

A variant of the SYT-SSX2 fusion gene in a case of synovial sarcoma.

Synovial sarcoma is a malignant soft tissue tumor harboring a tumor-specific fusion gene, SYT-SSX, of which exon 10 of the SYT gene is fused to exon 6 of the SSX gene is the common form. Here we report a case of synovial sarcoma with a novel form of the SYT-SSX2 fusion transcript, in which 75 bases were inserted at the common fusion junction. Computer analyses revealed that 15 bases were from intron 10 of the SYT gene, and 10 from the end of intron 4, and 50 from exon 5 of the SSX2 gene. Precise analyses of genomic breakpoints in SYT and SSX2 loci revealed that the reciprocal translocation creating the fusion gene was associated with a large deletion in both loci. The structure of SYT-SSX2 suggests that the fusion transcript in this case was created using a cryptic splicing acceptor site 15 bases upstream of the genomic fusion point, incorporating intronic sequences in mature mRNA. Reexamination of two variant SYT-SSX2 genes reported previously revealed that unknown sequences inserted at the common junction points were derived from intron sequences, as in the present case.

Mutation analysis of the RECQL4 gene in sporadic osteosarcomas.

Osteosarcoma (OS) is the most prevalent malignant tumor among cases of Rothmund-Thomson syndrome (RTS) with germline mutations of the RECQL4 gene, a member of the RecQ helicase family. We investigated the involvement of the RECQL4 gene in the development of OS unrelated to RTS. RECQL4 mRNA was detected in 9 of 9 OS cell lines by Northern blotting and 26 of 26 OS tumors by RT-PCR. Direct sequencing of the entire coding region along with flanking splice junctions and 13 small (< 100 bp) introns in 71 OS tumors revealed 2 sites with a single-base change causing an amino acid change (G1814A for R355Q and C2474T for P441S) and one site with a 6 bp inframe deletion (4837-42delTGCACC for CT857-8del). Identical genotypes were found in corresponding normal tissues in all cases, and the frequency of each allele was not significantly different between OS and control populations. Our data indicate that the RECQL4 gene is not a frequent target for somatic mutations in sporadic OS unrelated to RTS.