Paul C. Jutte

Biomaterial-Associated Infection: Locating the Finish Line in the Race for the Surface

This Review discusses approaches to developing infection-reducing biomaterials that strike a balance between host tissue integration and prevention of microbial attachment. NONE Biomaterial-associated infections occur on both permanent implants and temporary devices for restoration or support of human functions. Despite increasing use of biomaterials in an aging society, comparatively few biomaterials have been designed that effectively reduce the incidence of biomaterial-associated infections. This review provides design guidelines for infection-reducing strategies based on the concept that the fate of biomaterial implants or devices is a competition between host tissue cell integration and bacterial colonization at their surfaces.

Incidence, predictive factors, and prognosis of chondrosarcoma in patients with Ollier disease and Maffucci syndrome: an international multicenter study of 161 patients.

BACKGROUND Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. METHOD A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. RESULTS Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p = 0.00l). CONCLUSIONS Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with enchondromas located in long bones or axial skeleton, especially the pelvis, have a seriously increased risk of developing chondrosarcoma, and are identified as the population that needs regular screening on early detection of malignant transformation.

Critical factors in the translation of improved antimicrobial strategies for medical implants and devices

Biomaterials-associated infection incidence represents an increasing clinical challenge as more people gain access to medical device technologies worldwide and microbial resistance to current approaches mounts. Few reported antimicrobial approaches to implanted biomaterials ever get commercialized for physician use and patient benefit. This is not for lack of ideas since many thousands of claims to new approaches to antimicrobial efficacy are reported. Lack of translation of reported ideas into medical products approved for use, results from conflicting goals and purposes between the various participants involved in conception, validation, development, commercialization, safety and regulatory oversight, insurance reimbursement, and legal aspects of medical device innovation. The scientific causes, problems and impressive costs of the limiting clinical options for combating biomaterials-associated infection are well recognized. Demands for improved antimicrobial technologies constantly appear. Yet, the actual human, ethical and social costs and consequences of their occurrence are less articulated. Here, we describe several clinical cases of biomaterials-associated infections to illustrate the often-missing human elements of these infections. We identify the current societal forces at play in translating antimicrobial research concepts into clinical implant use and their often-orthogonal constituencies, missions and policies. We assert that in the current complex environment between researchers, funding agencies, physicians, patients, providers, producers, payers, regulatory agencies and litigators, opportunities for translatable successes are minimized under the various risks assumed in the translation process. This argues for an alternative approach to more effectively introduce new biomaterials and device technologies that can address the clinical issues by providing patients and medical practitioners new options for desperate clinical conditions ineffectively addressed by biomedical innovation.

Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study.

BACKGROUND Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations. PATIENTS AND METHODS Specialist centres collaborated to report prognostic factors and outcome for 113 patients. RESULTS Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P=0.046; hazard ratio (HR)=0.482 95% CI: 0.213-0.996) and death (P=0.004; HR=0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P=0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P<0.0001). Data on radiotherapy indications, dose and fractionation were insufficiently complete, to allow comment of its impact on outcomes. Median OS for patients with metastases at presentation was 3 years (95% CI: 0-4.25). CONCLUSIONS Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease.

Intercalary allograft reconstructions following resection of primary bone tumors: a nationwide multicenter study.

BACKGROUND Favorable reports on the use of massive allografts to reconstruct intercalary defects underline their place in limb-salvage surgery. However, little is known about optimal indications as reports on failure and complication rates in larger populations remain scarce. We evaluated the incidence of and risk factors for failure and complications, time to full weight-bearing, and optimal fixation methods for intercalary allografts after tumor resection. METHODS A retrospective study was performed in all four centers of orthopaedic oncology in the Netherlands. All consecutive patients reconstructed with intercalary (whole-circumference) allografts after tumor resection in the long bones during 1989 to 2009 were evaluated. The minimum follow-up was twenty-four months. Eighty-seven patients with a median age of seventeen years (range, 1.5 to 77.5 years) matched inclusion criteria. The most common diagnoses were osteosarcoma, Ewing sarcoma, adamantinoma, and chondrosarcoma. The median follow-up period was eighty-four months (range, twenty-five to 262 months). Ninety percent of tumors were localized in the femur or the tibia. RESULTS Fifteen percent of our patients experienced a graft-related failure. The major complications were nonunion (40%), fracture (29%), and infection (14%). Complications occurred in 76% of patients and reoperations were necessary in 70% of patients. The median time to the latest complication was thirty-two months (range, zero to 200 months). The median time to full weight-bearing was nine months (range, one to eighty months). Fifteen grafts failed, twelve of which failed in the first four years. None of the thirty-four tibial reconstructions failed. Reconstruction site, patient age, allograft length, nail-only fixation, and non-bridging osteosynthesis were the most important risk factors for complications. Adjuvant chemotherapy and irradiation had no effects on complication rates. CONCLUSIONS We report high complication rates and considerable failure rates for the use of intercalary allografts; complications primarily occurred in the first years after surgery, but some occurred much later after surgery. To reduce the number of failures, we recommend reconsidering the use of allografts for reconstructions of defects that are ≥15 cm, especially in older patients, and applying bridging osteosynthesis with use of plate fixation.

Successful treatment of Candida albicans-infected total hip prosthesis with staged procedure using an antifungal-loaded cement spacer.

We present a rare case of an immunocompetent host who developed a Candida albicans-infected total hip prosthesis. The infection could not be eradicated with debridement and extensive antifungal therapy. Our patient first underwent a resection of the proximal femur and local treatment with gentamicin-loaded cement beads. In a second procedure, a handmade cement spacer impregnated with voriconazole, amphotericin B, and vancomycin was placed. After 3 months of additional systemic antibiotic therapy, the patient remained afebrile, and a tumor prosthesis was placed. Six years postoperatively, she is doing well, walking with a small limp and no signs of recurrent infection. This is the first report on elution of voriconazole and amphotericin B from bone cement delivered at clinically significant concentrations for at least 72 hours.

Functional ability and physical activity in children and young adults after limb-salvage or ablative surgery for lower extremity bone tumors

Aim of our study was to compare functional ability and physical activity in children and young adults who underwent surgery for a malignant bone tumor that was located around the knee.

Hip fracture after radiofrequency ablation therapy for bone tumors: two case reports

Radiofrequency ablation (RFA) has become a valuable therapeutic modality in cancer treatment over the last decade. In orthopedic surgery, RFA is used for the treatment of benign bone tumors and bone metastases. Complications are rare and, to our knowledge, bone fracture as a complication due solely to RFA has not been reported to date. In this report we describe two patients with a fracture in the calcar region of the femur as a complication of RFA treatment for bone malignancies. Since RFA is applied increasingly often, it is important to report this risk of fracture as a complication of treatment of lesions in the femoral calcar.

The vascularised fibular graft for limb salvage after bone tumour surgery: a multicentre study

Vascularised fibular grafts (VFGs ) are a valuable surgical technique in limb salvage after resection of a tumour. The primary objective of this multicentre study was to assess the risk factors for failure and complications for using a VFG after resection of a tumour. The study involved 74 consecutive patients (45 men and 29 women with mean age of 23 years (1 to 64) from four tertiary centres for orthopaedic oncology who underwent reconstruction using a VFG after resection of a tumour between 1996 and 2011. There were 52 primary and 22 secondary reconstructions. The mean follow-up was 77 months (10 to 195). In all, 69 patients (93%) had successful limb salvage; all of these united and 65 (88%) showed hypertrophy of the graft. The mean time to union differed between those involving the upper (28 weeks; 12 to 96) and lower limbs (44 weeks; 12 to 250). Fracture occurred in 11 (15%), and nonunion in 14 (19%) patients. In 35 patients (47%) at least one complication arose, with a greater proportion in lower limb reconstructions, non-bridging osteosynthesis, and in children. These complications resulted in revision surgery in 26 patients (35%). VFG is a successful and durable technique for reconstruction of a defect in bone after resection of a tumour, but is accompanied by a significant risk of complications, that often require revision surgery. Union was not markedly influenced by the need for chemo- or radiotherapy, but should not be expected during chemotherapy. Therefore, restricted weight-bearing within this period is advocated.

Hemicortical Resection and Inlay Allograft Reconstruction for Primary Bone Tumors A Retrospective Evaluation in the Netherlands and Review of the Literature

BACKGROUND Selected primary tumors of the long bones can be adequately treated with hemicortical resection, allowing for optimal function without compromising the oncological outcome. Allografts can be used to reconstruct the defect. As there is a lack of studies of larger populations with sufficient follow-up, little is known about the outcomes of these procedures. METHODS In this nationwide retrospective study, all patients treated with hemicortical resection and allograft reconstruction for a primary bone tumor from 1989 to 2012 were evaluated for (1) mechanical complications and infection, (2) oncological outcome, and (3) failure or allograft survival. The minimum duration of follow-up was twenty-four months. RESULTS The study included 111 patients with a median age of twenty-eight years (range, seven to seventy-three years). The predominant diagnoses were adamantinoma (n = 37; 33%) and parosteal osteosarcoma (n = 18; 16%). At the time of review, 104 patients (94%) were alive (median duration of follow-up, 6.7 years). Seven patients (6%) died, after a median of twenty-six months. Thirty-seven patients (33%) had non-oncological complications, with host bone fracture being the most common (n = 20, 18%); all healed uneventfully. Other complications included nonunion (n = 8; 7%), infection (n = 8; 7%), and allograft fracture (n = 3; 3%). Of ninety-seven patients with a malignant tumor, fifteen (15%) had residual or recurrent tumor and six (6%) had metastasis. The risk of complications and fractures increased with the extent of cortical resection. CONCLUSIONS Survival of hemicortical allografts is excellent. Host bone fracture is the predominant complication; however, none of these fractures necessitated allograft removal in our series. The extent of resection is the most important risk factor for complications. Hemicortical resection is not recommended for high-grade lesions; however, it may be superior to segmental resection for treatment of carefully selected tumors, provided that it is possible to obtain adequate margins. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.