Osseointegrated Percutaneous Prosthetic System for the Treatment of Patients With Transfemoral Amputation: A Prospective Five-year Follow-up of Patient-reported Outcomes and Complications.

INTRODUCTION: Direct skeletal attachment of prostheses has previously been shown to improve patient-reported outcome (PRO) measures of individuals with transfemoral amputation (TFA) at 2-year follow-up. This prospective study reports the outcomes at 5-year follow-up. METHODS: A total of 51 patients (55 legs) with TFA were included in a prospective study. Complications, success rate, and PRO measures were followed for 5 years. RESULTS: The cumulative fixture survival rate at 5 years was 92%, and the revision-free survival rate was 45%. Thirty-four patients had 70 superficial infections. Eleven patients had 14 deep infections. Fifteen patients had mechanical complications. Four fixtures were removed (ie, one deep infection and three loosening). PRO measures showed significant improvements including more use of the prosthesis, better mobility, fewer issues, and improved physical health-related quality of life (all P < 0.0001) compared with baseline. CONCLUSION: Individuals with TFA at 5-year follow-up had significant improvement in PRO measures, but increases in deep infections and mechanical complications are concerning.

Osteomyelitis Risk in Patients With Transfemoral Amputations Treated With Osseointegration Prostheses.

BACKGROUND: Percutaneous anchoring of femoral amputation prostheses using osseointegrating titanium implants has been in use for more than 25 years. The method offers considerable advantages in daily life compared with conventional socket prostheses, however long-term success might be jeopardized by implant-associated infection, especially osteomyelitis, but the long-term risk of this complication is unknown. QUESTIONS/PURPOSES: (1) To quantify the risk of osteomyelitis, (2) to characterize the clinical effect of osteomyelitis (including risk of implant extraction and impairments to function), and (3) to determine whether common patient factors (age, sex, body weight, diabetes, and implant component replacements) are associated with osteomyelitis in patients with transfemoral amputations treated with osseointegrated titanium implants. METHODS: We retrospectively analyzed our first 96 patients receiving femoral implants (102 implants; mean implant time, 95 months) treated at our center between 1990 and 2010 for osteomyelitis. Six patients were lost to followup. The reason for amputation was tumor, trauma, or ischemia in 97 limbs and infection in five. All patients were referred from other orthopaedic centers owing to difficulty with use or to be fitted with socket prostheses. If found ineligible for this implant procedure no other treatment was offered at our center. Osteomyelitis was diagnosed by medical chart review of clinical signs, tissue culture results, and plain radiographic findings. Proportion of daily prosthetic use when osteomyelitis was diagnosed was semiquantitatively graded as 1 to 3. Survivorship free from implant- associated osteomyelitis and extraction attributable to osteomyelitis respectively was calculated using the Kaplan-Meier estimator. Indication for extraction was infection not responsive to conservative treatment with or without minor débridement or loosening of implant. RESULTS: Implant-associated osteomyelitis was diagnosed in 16 patients corresponding to a 10-year cumulative risk of 20% (95% CI 0.12-0.33). Ten implants were extracted owing to osteomyelitis, with a 10-year cumulative risk of 9% (95% CI 0.04-0.20). Prosthetic use was temporarily impaired in four of the six patients with infection who did not undergo implant extraction. With the numbers available, we did not identify any association between age, BMI, or diabetes with osteomyelitis; however, this study was underpowered on this endpoint. CONCLUSION: The increased risk of infection with time calls for numerous measures. First, patients should be made aware of the long-term risks, and the surgical team should have a heightened suspicion in patients with method-specific presentation of possible infection. Second, several research questions have been raised. Will the surgical procedure, rehabilitation, and general care standardization since the start of the program result in lower infection rates? Will improved diagnostics and early treatment resolve infection and prevent subsequent extraction? Although not supported in this study, it is important to know if most infections arise as continuous bacterial invasion from the skin and implant interface and if so, how this can be prevented? LEVEL OF EVIDENCE: Level IV, therapeutic study.

The clinical, radiological, microbiological, and molecular profile of the skin-penetration site of transfemoral amputees treated with bone-anchored prostheses.

The breach of the skin barrier is a critical issue associated with the treatment of individuals with transfemoral amputation (TFA) using osseointegrated, percutaneous titanium implants. Thirty TFA patients scheduled for abutment exchange or removal were consecutively enrolled. The aims were to determine the macroscopic skin signs, the presence of bacteria and the gene expression in abutment-adherent cells and to conduct correlative and comparative analyses between the different parameters. Redness and a granulation ring were present in 47% of the patients. Bacteria were detected in 27/30 patients, commonly in the bone canal. Staphylococcus aureus, coagulase-negative staphylococci, streptococci, and Enterococcus faecalis were the most common. A positive correlation was found between TNF-α expression and the detection of S. aureus. Staphylococcus aureus together with other bacterial species revealed a positive relationship with MMP-8 expression. A negative correlation was demonstrated between the length of the residual femur bone and the detection of a granulation ring and E. faecalis. A positive correlation was revealed between fixture loosening and pain and the radiological detection of endosteal bone resorption. Fixture loosening was also correlated with the reduced expression of interleukin-10 and osteocalcin. It is concluded that several relationships exist between clinical, radiological, microbiological, and molecular assessments of the percutaneous area of TFAs. Further long term studies on larger patient cohorts are required to determine the precise cause-effect relationships and unravel the role of host-bacteria interactions in the skin, bone canal and on the abutment for the longevity of percutaneous implants as treatment of TFA. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 578-589, 2017.

Implant survival, adverse events, and bone remodeling of osseointegrated percutaneous implants for transhumeral amputees.

BACKGROUND: Osseointegrated percutaneous implants provide direct anchorage of the limb prosthesis to the residual limb. These implants have been used for the rehabilitation of transhumeral amputees in Sweden since 1995 using a two-stage surgical approach with a 6-month interval between the stages, but results on implant survival, adverse events, and radiologic signs of osseointegration and adaptive bone remodeling in transhumeral amputees treated with this method are still lacking. QUESTIONS/PURPOSES: This study reports on 2- and 5-year implant survival, adverse events, and radiologic signs of osseointegration and bone remodeling in transhumeral amputees treated with osseointegrated prostheses. METHODS: Between 1995 and 2010, we performed 18 primary osseointegrated percutaneous implants and two implant revisions in 18 transhumeral amputees; of those, 16 patients were available for followup at a minimum of 2 years (median, 8 years; range, 2-19 years). These include all transhumeral amputees who have received osseointegrated prostheses and represented approximately 20% of the all transhumeral amputees we evaluated for potential osseointegration during that time; general indications for this approach included transhumeral amputation resulting from trauma or tumor, inability to wear or severe problems wearing a conventional socket prosthesis, eg, very short residual limb, and compliant patients. Medical charts and plain radiographs were retrospectively evaluated. RESULTS: The 2- and 5-year implant survival rates were 83% and 80%, respectively. Two primary and one revised implant failed and were removed because of early loosening. A fourth implant was partially removed because of ipsilateral shoulder osteoarthritis and subsequent arthrodesis. The most common adverse event was superficial infection of the skin penetration site (15 infections in five patients) followed by skin reactions of the skin penetration site (eight), incomplete fracture at the first surgery (eight), defective bony canal at the second surgery (three), avascular skin flap necrosis (three), and one deep implant infection. The most common radiologic finding was proximal trabecular buttressing (10 of 20 implants) followed by endosteal bone resorption and cancellization (seven of 20), cortical thinning (five of 20), and distal bone resorption (three of 20). CONCLUSIONS: The implant system presented a survivorship of 83% at 5 years and a 38% 5-year incidence of infectious complications related to the skin penetration site that were easily managed with nonoperative treatment, which make it a potentially attractive alternative to conventional socket arm prostheses. Osseointegrated arm prostheses have so far only been used in transhumeral amputations resulting from either trauma or tumor. Their use has not been tested and is therefore not recommended in transhumeral amputations resulting from vascular disease. This method could theoretically be superior to socket prostheses, especially in transhumeral amputees with very short residual humerus in which the suspension of a conventional prosthesis is difficult. Comparative studies are needed to support its potential superiority. Moreover, the radiological findings in this study need to be followed over time because some of them are of uncertain long-term clinical relevance.

Clinical course of nonvisceral soft tissue leiomyosarcoma in 225 patients from the Scandinavian Sarcoma Group.

BACKGROUND: Leiomyosarcoma of nonvisceral soft tissues is an uncommon malignant tumor; thus, only small numbers of cases have been reported. This study was based on a large series of patients from the Scandinavian Sarcoma Group Register acquired during a 15-year period (from 1986 to 2001). Follow-up information was available for all patients. METHODS: The authors analyzed the clinical features of 225 patients with cutaneous, subcutaneous, or deep-seated leiomyosarcoma of the extremities, trunk wall, and superficial parts of the head and neck region to determine the natural course of the disease. Only patients who received their treatment at a specialist sarcoma center were included. Re-evaluation of histopathology was performed. RESULTS: The age of the patients (121 women and 104 men) ranged from 20 years to 98 years (median, 70 years), and the tumors ranged in size from 0.6 cm to 35 cm (median, 4.0 cm). Eighty-two percent of the tumors were classified as high grade. The median follow-up for survivors was 5.5 years. The local treatment was adequate in 154 of 206 patients (75%) who were without metastasis at presentation. At 10 years, 84% of the 206 patients with localized disease at presentation were free from local recurrence, 66% remained metastasis free, and 49% were alive. Multivariate analysis showed that higher malignancy grade (P = .006), larger tumor size (P = .003), and deeper tumor location (P = .002) were correlated significantly with decreased metastasis-free survival, inadequate local treatment was correlated with local recurrence (P = .007), and high malignancy grade was correlated with decreased overall survival (P = .007). CONCLUSIONS: The long-term prognosis for patients with subcutaneous and deep-seated soft tissue leiomyosarcoma remains poor despite the ability to achieve adequate local control through nonmutilating surgery with or without radiotherapy.

Analysis of mural cell recruitment to tumor vessels.

BACKGROUND: Tumor blood vessels are both structurally and functionally abnormal compared with normal vessels. A limited support of mural cells may contribute to these abnormalities. Here, we characterized mural cell recruitment in 2 mouse tumor models and addressed the question of why tumor vessels fail to recruit a proper coat of mural cells. METHODS AND RESULTS: We studied mural cell recruitment to the vasculature of 2 transplantable mouse tumor models, T241 fibrosarcoma and KRIB osteosarcoma. We found that both tumors formed a vessel network with heterogeneous and highly abnormal organization of mural cells. Transplantation of tumors to mice expressing lacZ in mural cells demonstrated that these cells were host-derived. Although tumor vessel endothelium expressed PDGF-B, an embryonic mitogen for mural cells, only very few PDGFRbeta-positive cells were found to be associated with the developing tumor vasculature, suggesting a limited pool of recruitable mural cells. We tested whether exogenous mural cells could be recruited to tumor vessels by injecting mixtures of T241 tumor cells and embryonic mesenchymal cells isolated from mice expressing lacZ in mural cells. In the tumors that arose, lacZ-positive cells were efficiently recruited to the tumor vessels. CONCLUSIONS: T241 and KRIB tumors show a similar highly abnormal organization of vessel-associated mural cells. T241 tumor vessels seem highly capable of recruiting exogenously added mural cells. The sparse mural cell coat of tumor vessels may result from a limited pool of mural cells available for recruitment.