Primary Total Hip Arthroplasty for Legg-Calvé-Perthes Syndrome: 20 Year Follow-Up Study.

Background: Patients with Legg-Calvé-Perthes Syndrome (LCPS) are at an increased risk for developing osteoarthritis of the hip and undergoing total hip arthroplasty (THA) at an early age. Importantly, this younger age may put them at a higher risk for failure and revision surgery. The purpose of the study was to assess the clinical and radiographic outcomes as well as implant failure rate and risk for revision surgery at an average 20 years follow up. Methods: Data from LCPS patients treated with THA were collected including age, gender, operative date, revision date, as well as reason for and type of revision. Living patients filled the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires at the time of last follow-up. Radiographs were evaluated for lucencies, debonding, loosening, osteolysis, wear, heterotopic ossification and sclerosis. Results: Nineteen patients (20 hips) treated with THA were followed-up for a mean of 18.3 years (range, 10.1 - 36.2 years). Radiographic evidence of lucency of the acetabular component was seen in 70% of the patients and femoral cortical hypertrophy in 85% at last follow-up. The rate of revision for any reason was 35%, mostly due to aseptic acetabular loosening. Conclusions: Our findings support the use of THA for the treatment of OA in patients with LCPS, bearing in mind the potentially lower survival rate at 20 years as compared those treated with THA for primary OA. Further studies are needed to identify the possible causes of the high rate of cortical hypertrophy seen in this patient population.Level of Evidence: IV Therapeutic.

The 2018 Nicholas Andry Award: The Evidence Base for the Treatment of Developmental Dysplasia of the Hip: The Iowa Contribution.

This review summarizes evidence developed at the University of Iowa concerning the management and outcomes of developmental dysplasia of the hip beginning with the observations and analyses of Dr Arthur Steindler in the early 1900s. The strong evidence-based practice tradition established by Steindler 100 years ago continues as we critically evaluate our procedures and patient outcomes, only altering approaches when warranted by strong personal and research evidence. Our practice continues to be conservative in that we strive to produce the best environment possible for the hip to develop on its own and operate only when less invasive methods have failed.

5'-methylschweinfurthin G reduces chondrosarcoma tumor growth .

New treatment options are urgently required in the field of chondrosarcoma, particularly of chondrosarcomas with a well-differentiated hyaline cartilage-like extracellular matrix (e.g., collagen II and proteoglycan-rich) phenotype, notoriously resistant to drug penetration, and having potential of progression towards higher grade. We investigated the feasibility of using 5'-methylschweinfurthin G (MeSG) as a tumor suppressor agent in the Swarm rat chondrosarcoma, an intermediate- to high-grade chondrosarcoma model, having a hyaline cartilage-like phenotype. Tumor cell culture studies were performed to identify their proliferative and cytotoxicity sensitivity to MeSG. Tumor burden mice were treated with MeSG and analyzed for tumor growth, morphology and regression. The chondrosarcoma tumor cells had a half maximum cytotoxicity concentration (IC50 ) of 35 nM MeSG; approximately 300-fold less than freshly isolated rat chondrocytes (IC50 of 11 µM). Multiple injections of MeSG (20 mg/kg, body weight) resulted in reduced/eliminated tumor growth over a 17-day period in mice, and an 83% reduction (p = 0.023) in tumor mass. Three out of ten MeSG treated mice had complete elimination of tumor. Tumors of treated mice had a decrease in chondrosarcoma cell proliferation (p = 0.012) and an increase in cell death (p = 0.030) compared with tumors of control mice. These findings in an animal model demonstrate the effectiveness of MeSG for treatment of rat chondrosarcomas, and may have the potential use as a therapeutic option for the difficult-to-treat intermediate-to high-grade hyaline cartilage-like chondrosarcoma. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1283-1293, 2018.

The Ponseti Method in Low and Middle Income Countries: Challenges and Lessons Learned.

Diffusing a health care innovation like the Ponseti method in low and middle income countries requires more than the application of the traditional continuing medical education approach of providing lectures on the topic. Challenges include limited personnel, competing priorities, inadequate medical supplies, and limited resources. Experience has indicated that the best chances of success in establishing such a program include identifying and advising in-country "champions" to provide the leadership, energy, and direction to build the program.

Long-term results of tibialis anterior tendon transfer for relapsed idiopathic clubfoot treated with the Ponseti method: a follow-up of thirty-seven to fifty-five years.

BACKGROUND: Relapse of idiopathic clubfoot deformity after treatment can be effectively managed with repeat casting and tibialis anterior tendon transfer during early childhood. We evaluated the long-term effects on adult foot function after tibialis anterior tendon transfer for relapsed idiopathic clubfoot deformity during childhood. METHODS: Thirty-five patients (sixty clubfeet) in whom idiopathic clubfoot was treated with the Ponseti method from 1950 to 1967 were followed. At an average age of forty-seven years (range, thirty-seven to fifty-five years), the patients underwent a detailed musculoskeletal examination, radiographic evaluation, pedobarographic analysis, and surface electromyography (EMG). They also completed three quality-of-life patient questionnaires. RESULTS: Fourteen patients (twenty-five clubfeet, 42%) had required repeat casting and tibialis anterior tendon transfer in childhood for relapsed clubfoot deformity after initial casting and served as the study group. Twenty-one patients (thirty-five clubfeet, 58%) were successfully treated with initial casting without relapse (the reference group). No patient in either group had subsequent relapse or required additional operative intervention associated with clubfoot deformity. The mean ankle dorsiflexion was similar between the groups. Radiographically, the tendon transfer group showed a smaller mean anteroposterior talocalcaneal angle and slightly more talar flattening than the reference group with no associated clinical differences. Peak pressures, total force distribution, and surface EMG results were not significantly different between the groups. Outcome questionnaires demonstrated no significant difference between the groups. CONCLUSIONS: Tibialis anterior tendon transfer is very effective at preventing additional relapse of deformity without affecting long-term foot function of patients with idiopathic clubfoot.

The gothic arch: a reliable measurement for developmental dysplasia of the hip.

BACKGROUND: The "Gothic Arch" is a radio-graphic finding on AP pelvis x-rays postulated to be predictive of hip osteoarthritis. PURPOSE: The purpose of this study was to determine the reliability of measurement of the Gothic Arch in patients with no known hip pathology and patients with unilateral developmental dysplasia of the hip (DDH). PATIENTS AND METHODS: After obtaining IRB approval, nine skeletally mature patients (18 hips) with no known hip pathology were selected to serve as the control group. The AP pelvis x-rays at skeletal maturity of eight patients (16 hips) with unilateral DDH treated with closed reduction and casting comprised the comparison group. A digitizing program was designed to measure the Gothic Arch based on landmarks identified by the user. Two pediatric orthopaedic surgeons and two orthopaedic residents completed the program on two separate occasions. Intra-and interobserver reliability were determined using intraclass cor-relation coefficients (ICC) for continuous variables. RESULTS: Both the unilateral DDH group and the control group demonstrated excellent inter- and intraobserver reliability (ICC >0.70) for base, height, area, and orientation of the Gothic Arch, but poor reliability (ICC <0.40) for medial and lateral sharpness. CONCLUSION: The Gothic Arch can be reliably measured on AP pelvis x-rays of patients with normal and dysplastic hips. LEVEL OF EVIDENCE: III, Diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Management of idiopathic clubfoot after formal training in the Ponseti method: a multi-year, international survey.

BACKGROUND: Over the past decade, the Ponseti method has become the standard of care to treat clubfoot amongst orthopaedic surgeons around the world. Since 2001, the University of Iowa, under the guidance of the late Dr. Ignacio Ponseti, has been teaching the Ponseti method through a standardized training course. This study examines the current clubfoot management practices of those who have participated in the course and the effectiveness of formal Ponseti Training Courses. METHODS: An online survey was administered to practitioners who participated in the University of Iowa Ponseti Training Course from 2001-2011. RESULTS: One hundred and thirty-one practitioners responded to the survey representing 33 different countries and 70 different orthopaedic societies. Ninety-seven percent of practitioners reported currently using the Ponseti method as the preferred treatment for clubfoot. The respondents reported the average duration of each cast was 9.21 days (SD=9.04 d) and the average cast phase of treatment lasted 7.62 weeks (SD=2.43 w). Physicians were responsible for applying the cast 79% of the time. Braces were utilized following casting by 96% of physicians. The average age of brace use was 41 months (SD=16 m). The reported relapse rate was 21% (SD=17%). Ninety-seven percent of practitioners changed their practice after completion of the course. The preferred method prior to the course was surgical release (48%). Sixty-one percent of practitioners preferred review articles as an additional educational support; 49% preferred training videos. Sixty-seven percent believed an 'on-site' visit to their hospital by an expert in the Ponseti method would be very beneficial. Seventy-three percent suggested improving the course by providing more 'hands on' experience. Ninety-five percent of practitioners were satisfied with the course. CONCLUSION: The Ponseti Training Course is an effective way to educate physicians on how to treat clubfoot with the Ponseti method. However, improvements should include more hands-on learning as well as an 'on-site' visit with an expert Ponseti practitioner.

Early effects of a 'train the trainer' approach to Ponseti method dissemination: a case study of Sri Lanka.

BACKGROUND: The Ponseti method has been established as the standard of care for the treatment of clubfoot in many developed countries for its utility, cost-effectiveness, and efficiency. However, despite its being described as the gold-standard for clubfoot treatment, there are still many areas of the world bereft in formal training in the Ponseti method. This is especially important since 80% of patients with clubfoot are born in developing countries where the need is the greater for experienced providers. This study analyzes a 'Train the Trainer' approach, specifically in the island nation of Sri Lanka, as a model for future dissemination of the Ponseti method throughout the developing world. METHODS: A rapid ethnographic study design that included interviews, focus groups, and direct observation of 162 patients and healthcare practitioners directly involved with clubfoot care was conducted. RESULTS: The average age of the patients at the time of the interview was 75.4 weeks old (SD = 149.2), traveled 45.2 kilometers (SD = 49.8) to receive their care, and received 4 casts (SD = 2.2) for correction of the deformity. Since the initiation of the 'Train the Trainer' educational program, clubfoot clinics reportedly grew from 6-7 patients per week to over 60 patients per week. The majority of this patient population growth was attributed to word of mouth. Major barriers to the method included casting materials, bracing materials, and a lack of a dedicated area of the clinic to conduct tenotomies under local anesthesia. Of note, cost was not cited as a major barrier. CONCLUSION: Early evaluation suggests great utility of the 'Train the Trainer' method - especially regarding an increased patient demand for treatment. However, further studies are necessary to understand the long-term utility of this training methodology.

Descriptive epidemiology of clubfoot in Peru: a clinic-based study.

congenital clubfoot is the most common birth defect of the musculoskeletal system and affects 1 in every 1000 live births each year.(1) Although there have been numerous studies of investigation, the etiology and pathogenesis of clubfoot remains unknown. To date, no epidemiological studies have been conducted in Peru to assess possible genetic and environmental risk factors associated with this deformity. The purpose of this study was to evaluate specific environmental and socioeconomic factors that may increase the risk of clubfoot. A descriptive clinic-based study was conducted using structured questionnaires given to biological mothers of clinically confirmed clubfoot patients (n=72) and biological mothers of children between ages 0-18 with no first or second degree family history of clubfoot as controls (n=103). Phenotypic data from clubfoot subjects were also collected. We found that males were twice as likely to have clubfoot as females, and half of all clubfoot patients had bilateral clubfoot. There was no significant difference in the rate of left vs. right clubfoot. Infant birth in the winter months correlated with an increased risk of clubfoot (p=0.01476). Maternal characteristics found to be significantly associated with increased risk of clubfoot were young maternal age at conception (p=0.04369) and low maternal education (p=0.003245). Young paternal age also had a correlation with increased risk of clubfoot in the child (p=0.0371). Both paternal smoking (p=0.00001) and the presence of any household smoking (p=0.00003) were strongly associated with an increased risk of clubfoot.

Barriers to the Ponseti method in Peru: a two-year follow-up.

Idiopathic clubfoot affects approximately 100,000 children each year and is one of the leading causes of disability worldwide. The Ponseti method is an inexpensive, non-surgical treatment that, when executed correctly, is more than 95% effective; however, in Peru, a developing country where a low-cost alternative is greatly needed, physicians report up to 30% of patients do not complete treatment. This study involved semi-structured interviews with 25 physicians who practice the Ponseti Method in Peru to discuss obstacles for the method in their country. The most frequent obstacles to the Ponseti method in Peru reported by physicians included lack of physicians trained in the Ponseti method in the country, patient transportation and distance to treatment centers, and lack of parental knowledge of the Ponseti method. These data suggest the need to train more physicians in Peru, particularly in the provinces. Increasing access to trained physicians in provincial areas may reduce the financial and travel burden of parents to help increase compliance with treatment.

Secondary chondrosarcoma of the pelvis arising from a solitary exostosis in an 11-year-old patient: a case report with 5-year follow-up.

Although conversion of an osteochondroma to chondrosarcoma is a well-described rare occurrence, it is usually associated with syndromes such as multiple hereditary exostoses and is much more common after maturity. We present here a rare case of secondary pelvic chondrosarcoma arising from a solitary exostosis in a pediatric patient. An 11-year-old, otherwise healthy, female was referred to our clinic for evaluation of a pelvic mass detected on a radiograph. The radiographs obtained by the referring physician demonstrated a large lesion arising from the right superior pubic ramus, which was visible but not identified on an abdominal radiograph several years prior. Histopathologic analysis showed chondrosarcoma which was supported by an additional opinion to rule out chondroblastic osteosarcoma. The patient was treated with wide resection without adjuvant therapy and is doing well with no evidence of recurrence five years post-operatively. There have been only a few small case series describing chondrosarcoma in the pediatric patient. Even rarer are descriptions of secondary chondrosarcoma with only occasional cases reported as part of larger case series. Chondrosarcoma is a rare and difficult diagnosis in the pediatric patient. There is often considerable debate between chondrosarcoma and chondroblastic osteosarcoma, and the treatment implications of differentiating these diagnoses are of paramount importance.

The current management of idiopathic clubfoot revisited: results of a survey of the POSNA membership.

BACKGROUND: In 2001, the members of the Pediatric Orthopaedic Society of North America (POSNA) were surveyed regarding their approach to treating idiopathic clubfoot deformity. Since that time, several studies have advocated a change in the approach to treating this deformity, moving away from surgical release and toward less invasive methods. The purpose of this study was to assess the recent approach to treating clubfoot among the POSNA membership. METHODS: A survey was emailed to all POSNA members to define their current treatment of idiopathic clubfoot deformity. RESULTS: We received 323 responses. Ninety-three percent of participants were fellowship trained and were in practice for an average of 17.2 years. On an average, physicians reported each treating 23.5 new clubfoot patients during the year of survey. Nearly all (96.7%) of those surveyed stated that they use the Ponseti treatment method. The average time to initial correction was estimated at 7.1 weeks. Eighty-one percent of patients were estimated to require a tenotomy; 52.7% were performed under general anesthesia or conscious sedation, whereas 39.4% were done under local. Those surveyed estimated that 22% of clubfeet relapsed and 7% required a comprehensive release. Seventy-five percent of the respondents stated that their current treatment approach differed from how they were trained, and 82.7% were trained in the Ponseti method in the last few years. CONCLUSIONS: Our study provides convincing evidence that a large majority of pediatric orthopaedic surgeons now prefer the Ponseti method to treat idiopathic clubfoot and indicates that the move away from extensive release surgery occurred during the past decade. LEVEL OF EVIDENCE: Not applicable.

Treatment results of late-relapsing idiopathic clubfoot previously treated with the Ponseti method.

BACKGROUND: Idiopathic clubfoot has a stubborn tendency for relapse, with most relapses happening within the first few years. However, a few patients relapse later, adding to the complexity of management. This study investigates the treatment results of relapsing clubfoot deformity after age 4. METHODS: Thirty-nine patients (60 feet) met the inclusion criteria. Age at initial treatment, previous treatment, number of casts and tenotomies, length of bracewear, and relapse presentation were recorded. Treatment of late relapse followed 1 of the 5 courses: (1) observation only (4 feet); (2) bracing (26 feet); (3) casting followed by bracing (7 feet); (4) casting followed by tibialis anterior tendon transfer (TATT) with or without open tendo Achilles lengthening (TAL) (8 feet); or (5) primary TATT±TAL (15 feet). Of the 37 feet treated initially with observation, bracing, or casting, 33 went on to have TATT (89%). Multiple other concurrent procedures were performed according to the specific deformities. These included plantar fasciotomy (6 feet), extensor hallicus longus recession (5 feet), limited posterior release 5 feet, and others (3 feet). Five feet underwent revision surgery after TATT, 2 of which ended in triple arthrodeses. RESULTS: Average age at final follow-up was 23.3 years (range, 8.5 to 50.6 y). Ninety percent of patients wore regular shoes, 41% had pain with activities, but only 18% were limited in function by their feet. Average ankle dorsiflexion was 6 degrees (range, -15 to 25 degrees). Mild residual deformities were noted in 55% of feet. CONCLUSIONS: This challenging group of patients with apparently persistent deforming biology achieves acceptable results with individualized evaluation and treatment of their foot deformities. LEVEL OF EVIDENCE: Therapeutic level IV.

Relapse after tibialis anterior tendon transfer in idiopathic clubfoot treated by the Ponseti method.

BACKGROUND: The Ponseti method for clubfoot correction has demonstrated excellent results. However, relapses are common and continue to be the most important problem facing clubfoot practitioners. Relapses usually require repeated casting and/or surgical intervention with tibialis anterior tendon transfer (TATT). However, recent data on relapses suggest that performing a successful TATT may not be a definitive cure as there may be other processes, such as neuromuscular deficits, that may result in subsequent relapses. METHODS: The authors reviewed 66 patients (102 clubfeet) treated by TATT for clubfoot relapses after successful initial treatment by the Ponseti method. Ten patients (15 clubfeet) experienced a subsequent relapse. Demographic, clinical, and treatment data was recorded. RESULTS: These patients had a tendency toward a greater number of casts at initial treatment (P=0.14) and they underwent relapse surgery earlier than those who did not relapse after TATT (P=0.05). Two of these patients had a neuromyopathy, diagnosed by muscle biopsy. The treatment of post-TATT relapse included casting (6 patients), ankle foot orthotic (4 patients), physical therapy (2 patients), or bracing (1 patient). One patient was treated by osteotomies of the cuboid and medial cuneiform and 1 patient had a peroneus longus to peroneus brevis tendon transfer. CONCLUSIONS: Performing a TATT may not be the definitive treatment for clubfoot relapses as neuromuscular deficits may be involved. In addition, these patients may be at an increased risk of relapse due to the earlier age at which TATT was performed. When there is a high index of suspicion, prompt diagnosis with muscle biopsy is warranted. LEVEL OF EVIDENCE: Level III (Case-control study).

Swarm rat chondrosarcoma cells as an in vivo model: lung colonization and effects of tissue environment on tumor growth.

Swarm rat chondrosarcoma cells have been used extensively for biochemical studies of extra-cellular matrix metabolism in cartilage. However, these cells also possess tumor-like behavior in vivo and are useful in investigation of chondrosarcoma biology. the current study was designed to develop a metastatic model using swarm rat chondrosarcoma cells, and to assess the effect of tissue-environment on tumor behavior in vivo. Tumors were implanted subcutaneously or into bone, and animals were assessed radiographically and microscopically for tumor growth and metastasis. The subcutaneous tumor grew to an average mass of 35 g, while tumor implanted into bone grew 75 mg. Transplantation of the cells into the bone led to extensive bone remodeling with invasion of the medullary cavity and destruction of the bone cortex. Light microscopy demonstrated no significant differences in the number of mitoses, cellular atypia or extracellular matrix staining between the two sites of tumor implantation. Interestingly, lung colonization was observed in none of the animals in the subcutaneous tumor injection group, while tumors colonized the lungs in 95% of the rats with tumor injected into bone. Analysis of cDNA libraries from subcutaneous and bone-transplanted tumors demonstrated a complex and diverse array of expressed transcripts, and there were significant differences in gene expression between tumors at different sites. The results of this study suggest swarm rat chondrosarcoma is a model that resembles human chondrosarcoma mimicking its ability to infiltrate and remodel local bone and to colonize the lungs. Furthermore, the interaction between host-tissue and tumor cells plays a major role in the tumor behavior in this model. Identifying these interactions will lead to further understanding of chondrosarcoma and contribute to therapeutic targets in the future.

Evaluation of the progress and challenges facing the Ponseti method program in Vietnam.

INTRODUCTION: In 2003, an ICRC-SFD Ponseti program was introduced in southern Vietnam. Additional programs were introduced by the Prosthetics Outreach Foundation and independently by physicians trained at our center. The purpose of this study was to evaluate the impact, progress and challenges facing Ponseti practitioners and patients' family members in Vietnam. In addition, web-conferencing (Ponseti Virtual Forum) for continued medical education in the method was also assessed. METHODS: Multiple questionnaires were developed to conduct face-to-face practitioner interviews, focus group interviews, and parental interviews. Observation was done at multiple site clinics to determine or confirm additional challenges faced by practitioners. Web conferencing was introduced to sites in Ho Chi Minh City and Da Nang City. RESULTS: The number of clubfoot patients treated with the Ponseti method has increased over time with approximately 1,252 infants treated between 2003 and 2010. Specific challenges were identified relating to communication, networking, distance and transportation, and finances for both practitioners and parents. The PVF was not only found to facilitate rapid, relevant dissemination of medical knowledge--thus increasing physician and patient satisfaction--but it may also be found to act as an interface in which medical culture, insight, and compassion are shared benefiting all virtual forum participants. CONCLUSION: The identified progress and challenges mirrored that of similar studies done in other countries with several factors affecting progress. Focusing on improving communication channels and networking while working with the ministry of health may improve the facilitation of the Ponseti method in Vietnam. Further implementation and evaluation of the PVF may act as a guide for current and future programs in Vietnam or other countries.

Qualitative assessment of the challenges to the treatment of idiopathic clubfoot by the Ponseti method in urban India.

The Ponseti method of clubfoot treatment has been shown to be a very safe, effective and minimally invasive technique when performed in medical centers in Europe and North America. However, only a limited number of studies have helped identify the challenges for effective treatment with the Ponseti method in India. In this study a qualitative approach was used through distribution of questionnaires, personal interviews and focus groups with orthopedic surgeons (in urban centers) and parents of patients with clubfoot. The following factors were evaluated: (i) physician education, (ii) alternative methods of treatment/modification of the Ponseti technique, (iii) compliance by parents, (iv) treatment in underserved areas, (v) culture, (vi) community knowledge of clubfoot, and (vii) the health care system in India. The results showed that all of the factors evaluated hindered outcomes for patients; however, parent's compliance with bracing, lack of proper rural clubfoot treatment clinics, poverty and physician education were the most prominent challenges. The results of this study can be used to implement specific strategies to improve the diffusion and implementation of the Ponseti method for treating clubfoot throughout India.

The Ponseti method in Latin America: initial impact and barriers to its diffusion and implementation.

The Ponseti method for correcting clubfoot is a safe, effective, and minimally invasive treatment that has recently been implemented in Latin America. This study evaluates the initial impact and unique barriers to the diffusion of the Ponseti method throughout this region. Structured interviews were conducted with 30 physicians practicing the Ponseti method in three socioeconomically diverse countries: Chile, Peru and Guatemala. Since learning the Ponseti method, these physicians have treated approximately 1,740 clubfoot patients, with an estimated 1,705 (98%) patients treated using the Ponseti method, and 35 (2%) patients treated using surgical techniques. The barriers were classified into the following themes: physician education, health care system of the country, culture and beliefs of patients, physical distance and transport, financial barriers for patients, and parental compliance with the method. The results yielded several common barriers throughout Latin America including lack of physician education, physical distance to the treatment centers, and financial barriers for patients. Information from this study can be used to inform, and to implement and evaluate specific strategies to improve the diffusion of the Ponseti method for treating clubfoot throughout Latin America.

Expanding endoprosthesis for pediatric musculoskeletal malignancy: current concepts and results.

Surgical treatment and reconstruction of a pediatric patient with a bone malignancy should consider many patient and tumor specific factors. Surgical treatment should be geared first and foremost towards obtaining wide margins. To that end the options can include amputation, rotationplasty and prosthetic reconstruction. Advances in adjuvant chemotherapy for musculoskeletal malignancy in pediatric patients has increased acceptance of limb-salvage procedures as a viable option for treatment, whereas limb ablation was formerly the only acceptable means for attaining disease eradication. The advent of the expandable prosthesis has gained significant interest due to the appeal of improved cosmesis and potential for equal limb length at skeletal maturity. The latest generation implants allow for non-invasive lengthening with an outpatient procedure and are generally very well-tolerated by the patient. Review of current literature demonstrates that this procedure has generally good patient reported outcomes but has a high complication rate. Aseptic loosening and mechanical dysfunction are common modes of failure and often necessitate one or more large revision surgeries. Further improvement in implant design and biomaterials may decrease the incidence of these complications and promising work in these areas is ongoing. When discussing this specific option, patients and family should be counseled regarding the likelihood of future surgeries to manage the expected complications.

Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors.

BACKGROUND: Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established--namely, the Swarm Rat Chondrosarcoma (SRC)--and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. METHODS: To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. RESULTS: The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-ß4, c-fos, and CTGF may play in chondrosarcoma development and progression. CONCLUSION: This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-ß4 may have a role in chondrosarcoma metastasis.