[Growing prostheses after sarcoma resection in children and adolescents]. / Wachstumsprothesen nach Sarkomresektionen im Kindes- und Jugendalter.

BACKGROUND: Growing prostheses are regarded as a valuable alternative to amputation and rotationplasty for the treatment of primary malignant bone and soft-tissue sarcomas in childhood. During the last three decades different devices have been introduced and technically improved from invasively to non-invasively extendable prostheses. THE CURRENT SITUATION OF STUDIES: Despite the long period, only 21 peer-reviewed publications could be detected containing relevant numbers and results. In these papers, 590 patients with mean follow-up times of 81.1 months were reported who had been fitted with growing prostheses at the age of 12.6 years. Besides satisfactory functional results (78.3 out of 100 MSTS points) there was a high complication rate of 27.3% infections and 22.4% mechanical failure. COMPLICATIONS: This increasing risk of infection over a long follow-up period, represents the biggest drawback of this method and, therefore, needs to be discussed extensively with the patients and parents when considering this procedure as an alternative to ablative surgery.

[General diagnostic work-up for benign tumors of the musculoskeletal system]. / Allgemeine diagnostische Grundlagen bei benignen Tumoren des Bewegungsapparats.

INTRODUCTION: Benign bone tumors are heterogeneous and have different biological behaviors. Treatment requires knowledge of the principle diagnosis and clinical behavior to avoid, on the one hand, overtreatment and, on the other hand, incorrect diagnosis of a potentially malignant tumor. METHODS: Bone tumors of stage I (according to Enneking) should be observed clinically and radiologically. For stage II and stage III lesions, a biopsy should be performed, based on the corresponding oncological guidelines. RESULTS AND CONCLUSION: Soft tissue tumors have a different radiological behavior (especially in magnetic resonance images): while a lack of sharp cortical margins in bone tumors indicates an aggressive behavior, sharp margins in soft tissue tumors should not be misinterpreted as benign tumors. Subfascial soft tissue tumors, tumors larger than 2 cm, growing tumors, and persisting tumors after trauma require biopsy.

Clinical signs of neurofibromatosis impact on the outcome of malignant peripheral nerve sheath tumors.

OBJECTIVE: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of sarcoma, with a poor outcome. MPNST are regarded as being sporadic or associated with neurofibromatosis type 1 (NF1). Few comparative overall-survival (OS) data in these 2 subsets of MPNST patients exist. The aim of this retrospective study was to assess OS in sporadic and NF1-associated MPNST patients. METHODS: Fourteen consecutive patients with initial localized as well as initial metastatic MPNST were diagnosed and treated in our department. Patients with sporadic MPNST were assigned to group A and those with NF1-associated MPNST to group B. RESULTS: Eight versus 6 patients were allocated to groups A and B. Primary tumors were located on the extremities in all but 1 patient. Two patients in group A and 4 patients in group B experienced a relapse. Four patients died in each of the 2 groups. Median follow-up was 66.2 and 57.2 months in group A and group B, respectively. Median OS in group A was 46.9 months versus 12.7 months in group B. CONCLUSIONS: In this small, single-center study, sporadic-MPNST patients had a longer median OS than those with NF1-associated MPNST.

High fibrinogen levels are associated with poor survival in patients with liposarcoma.

The aim of this study was to evaluate whether (preoperative) plasma levels of fibrinogen, an essential clotting and acute phase protein, are associated with the prognosis of patients with a liposarcoma, a subtype of sarcoma derived from adipose tissue. We performed a retrospective cohort study of 158 patients with liposarcoma treated at the Department of Orthopaedics of the Medical University of Vienna in Austria from May 1994 to October 2021. Kaplan-Meier curves as well as uni- and multivariable Cox proportional hazard models were performed to evaluate the association between fibrinogen levels and overall survival. Elevated fibrinogen was associated with adverse overall survival in cause specific hazards analysis of mortality (hazard ratio [HR] per 10 mg/dL increase: 1.04; 95% CI 1.02-1.06; p < 0.001). This association prevailed in multivariable analysis after adjustment for AJCC tumor stage (HR 1.03; 95% CI 1.01-1.05; p = 0.013). Increasing levels of fibrinogen, a routinely available and inexpensive parameter, predicts the risk of mortality in patients with liposarcoma.

Surgical Site Infection in Patients Managed with an Endoprosthesis for the Treatment of Cancer: Evaluation of Patient, Disease, and Index Surgical Factors.

BACKGROUND: Surgical site infection (SSI) after segmental endoprosthetic reconstruction in patients treated for oncologic conditions remains both a devastating and a common complication. The goal of the present study was to identify variables associated with the success or failure of treatment of early SSI following the treatment of a primary bone tumor with use of a segmental endoprosthesis. METHODS: The present study used the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) data set to identify patients who had been diagnosed with an SSI after undergoing endoprosthetic reconstruction of a lower extremity primary bone tumor. The primary outcome of interest in the present study was a dichotomous variable: the success or failure of infection treatment. We defined failure as the inability to eradicate the infection, which we considered as an outcome of amputation or limb retention with chronic antibiotic suppression (>90 days or ongoing therapy at the conclusion of the study). Multivariable models were created with covariates of interest for each of the following: surgery characteristics, cancer treatment-related characteristics, and tumor characteristics. Multivariable testing included variables selected on the basis of known associations with infection or results of the univariable tests. RESULTS: Of the 96 patients who were diagnosed with an SSI, 27 (28%) had successful eradication of the infection and 69 had treatment failure. Baseline and index procedure variables showing significant association with SSI treatment outcome were moderate/large amounts of fascial excision ≥1 cm2) (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.001), use of local muscle/skin graft (OR,11.88 [95% CI, 1.83 to 245.83]; p = 0.031), and use of a deep Hemovac (OR, 0.24 [95% CI, 0.05 to 0.85]; p = 0.041). In the final multivariable model, excision of fascia during primary tumor resection was the only variable with a significant association with treatment outcome (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.018). CONCLUSIONS: The results of this secondary analysis of the PARITY trial data provide further insight into the patient-, disease-, and treatment-specific associations with SSI treatment outcomes, which may help to inform decision-making and management of SSI in patients who have undergone segmental bone reconstruction of the femur or tibia for oncologic indications. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ultrasound guidance improves the accuracy of the acromioclavicular joint infiltration: a prospective randomized study.

Degeneration of the acromioclavicular joint (AC) often causes impaired shoulder function and pain. Its infiltration results in reportedly beneficial short-term effects. Misplacement of infiltrations is observed in high numbers. A previous study showed high accuracy of infiltrations of one surgeon comparing conventional palpation technique to ultrasound guidance. This study evaluates if ultrasound-guided AC joint infiltration is feasible for therapists of different levels of experience and if the accuracy can be increased. One hundred and twenty AC joints of 60 cadavers were enrolled into a prospective, randomized observer-blinded study. Six therapists of three different levels of experience infiltrated 20 AC joints each. Half of them were infiltrated after palpation of the joint space, half of them were ultrasound-guided infiltrated. Controls were performed pre- and post-infiltration by an independent radiologist. In total, accurate infiltration was observed in 70%. In 25%, misplacement of the infiltration was recorded in the palpation-, in 2% in the ultrasound- and in 3% in both groups. The difference between the two groups was significant (P = 0.009). Ultrasound-guided infiltration to the AC joint is significantly more accurate than conventional palpation technique. This method is simple, efficient and can be applied by therapists of all levels of experience.

[Modular tumor prostheses of the humerus]. / Modulare Tumorprothesen des Humerus.

The humerus is a common location of musculoskeletal tumors. Modular prostheses of the humerus, besides APC and biological reconstructions, allow restoration of resulting bone defects. The functional outcome is determined by the extent of bone and soft tissue loss. Anatomical shoulder prostheses have a limited abductor function, while shoulder function could be improved by an inverse prosthetic design and implants for ligament repair. Elbow prostheses provide satisfactory function. Our own results in 101 patients showed a 23% revision rate. The median overall survival was 171 months with an overall 5-year survival of 53%. With respect to good oncological outcomes modular reconstruction of the humerus is a feasible treatment option for cancer patients.

Surgical Outcome and Oncological Survival of Osteofibrous Dysplasia-Like and Classic Adamantinomas: An International Multicenter Study of 318 Cases.

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

[Upper-extremity amputation in tumours of the shoulder and upper arm--experiences of the Vienna Bone Tumour Registry]. / Die Amputation an der oberen Extremität bei Tumoren der Schulter und des Oberarmes--Erfahrungen aus dem Wiener Knochengeschwulstregister.

Malignant lesions of the bones and soft tissues require radical or wide resection to achieve adequate therapy. Due to the many developments in terms of adjuvant modalities, diagnostics and surgical expertise today there are several modes of therapy as alternatives to amputation in the treatment of malignant tumours of the shoulder and upper arm. After resection of smaller tumours excellent functional results can be obtained by the use of modular endoprostheses, whereas large neoplasms adjacent to the neurovascular bundle require resection-replantation to allow salvage of the hand. Within the Vienna Bone Tumour Registry, 100 patients out of a total of more than 6500 have been treated for such lesions: 62 received an endoprostheses, 18 resection-replantation and 20 amputation. In cases of primary malignant tumours the incidence of lung metastases was higher in the resection-replantation group (50 %) and amputation group (42 %) than in the prostheses group (11 %), which has been linked to larger tumour size in the former two groups. Radical or wide resections were obtained in 95 % of the prostheses group, as compared to 75 % and 78 % in the amputation group and the resection-replantation group, respectively, due to invasion into the neurovascular bundle. Over time the number of amputations decreased simultaneously with the increase of endoprostheses whereas the number of resection-replantations remained equal at our institution. Amputation today still plays a crucial role in the treatment of intralesionally resected tumours, as surgical contamination can make limb salvage impossible. Therefore, the importance of biopsy in the therapeutical algorithm of bone and soft tissue tumours has to be emphasised again.

The outcome of the surgical treatment of pelvic chondrosarcomas: a competing risk analysis of 58 tumours from a single centre.

AIMS: Few studies dealing with chondrosarcoma of the pelvis are currently available. Different data about the overall survival and prognostic factors have been published but without a detailed analysis of surgery-related complications. We aimed to analyse the outcome of a series of pelvic chondrosarcomas treated at a single institution, with particular attention to the prognostic factors. Based on a competing risk model, our objective was to identify risk factors for the development of complications. PATIENTS AND METHODS: In a retrospective single-centre study, 58 chondrosarcomas (26 patients alive, 32 patients dead) of the pelvis were reviewed. The mean follow-up was 13 years (one week to 23.1 years). RESULTS: A total of 26 patients (45%) were alive and 32 patients (55%) had died. Overall survival was 76%, 55% and 45% at one, five and ten years post-operatively, respectively. In a competing risk model the cumulative risk of the development of a surgery-related complication was 64% at six months and 69% at one year, post-operatively, respectively. Endoprosthetic reconstruction was a significant risk factor for the development of complications (p = 0.006). Complications were not significantly related to age or the location or grade of the tumour (p = 0.823, p = 0.976, p = 0.858). The development of complications did not have a negative effect on survival (p = 0.147). CONCLUSION: This is the first study with competing risk analysis of surgery-related complications in patients with a pelvic chondrosarcoma. The surgery in these patients remains prone to complications. Endoprosthetic reconstruction significantly increases the risk of the development of complications (p = 0.006). A competing risk model showed that the development of complications does not have a negative influence on overall survival (p = 0.147). An aggressive, surgical resection with the goal of achieving wide margins whenever possible remains the mainstay of treatment. Cite this article: Bone Joint J 2017;99-B:686-96.

Pelvic reconstruction following resection of malignant bone tumours using a stemmed acetabular pedestal cup.

AIMS: Pelvic reconstruction after the resection of a tumour around the acetabulum is a challenging procedure due to the complex anatomy and biomechanics. Several pelvic endoprostheses have been introduced, but the rates of complication remain high. Our aim was to review the use of a stemmed acetabular pedestal cup in the management of these patients. PATIENTS AND METHODS: The study involved 48 patients who underwent periacetabular reconstruction using a stemmed pedestal cup (Schoellner cup; Zimmer Biomet Inc., Warsaw, Indiana) between 2000 and 2013. The indications for treatment included a primary bone tumour in 27 patients and metastatic disease in 21 patients. The mean age of the patients at the time of surgery was 52 years (16 to 83). RESULTS: At a median follow-up of 6.6 years (95% confidence interval 4.6 to 8.2), local control was achieved in all patients; 19 patients had died (16 of disease). Complications occurred in 19 patients (40%), of which deep infection was the most common, affecting eight patients (17%). Seven patients (15%) had a dislocation of the hip. Aseptic loosening was found in three patients (6%). Two (4%) underwent hindquarter amputation for non-oncological reasons. The risk of revision, with death being treated as a competing event, was 28% at one year, 39% at five years and 48% at ten years post-operatively. The mean Musculoskeletal Tumour Society Score at final follow-up was 71% (27% to 93%). CONCLUSION: This type of reconstruction is a satisfactory option for the treatment of patients with a periacetabular tumour. There remains, however, a high rate of complication, which may be reduced by future modifications of the device such as silver coating and tripolar articulation. Cite this article: Bone Joint J 2017;99-B:841-8.

Survival, failure modes and function of combined distal femur and proximal tibia reconstruction following tumor resection.

BACKGROUND: Tumor spread to the knee joint or skip metastasis to the adjacent bones of the knee require reconstruction with combined distal femur and proximal tibia replacements. The literature on implant survival and failure modes with this type of reconstruction is sparse. The goals of this study were to determine the implant survival, the different failure modes and the functional outcome of this megaendoprosthetic reconstruction. PATIENTS AND METHODS: Thirty-nine patients with combined distal femur and proximal tibia reconstruction were retrospectively reviewed. Median follow-up was 8.8 years (quartiles 4.7-15.5 years). Twenty-one patients received combined distal femur and proximal tibia reconstruction as a primary mode of reconstruction, 18 patients as revision surgery after failed tumor prosthesis. For survival estimations, competing risk analyses were performed. RESULTS: The revision-free survival at five years was 42% (95% CI 22%-56%) and implant survival with exchange of the original implant was 54% (95% CI 35%-68%). Five-year revision-free survival for soft tissue failure was 72% (95% CI 52%-84%), for infection 67% (95% CI 48%-80%), for structural failure 82% (95% CI 63%-91%), for aseptic loosening and tumor progression 97% (95% CI 82%-99%), respectively. Patients with revision surgery had higher risk for infection (p < 0.001), structural failure (p = 0.037) and shorter revision-free- (p = 0.025) and implant-survival (p = 0.006). Limb survival at 20 years was 94%. Mean musculoskeletal Tumor Society score was 76%. CONCLUSION: Despite high failure rates with short revision-free survivals, combined distal femur and proximal tibia reconstruction achieved longtime limb survival in the majority of patients with satisfying function.

The stability of the hip after the use of a proximal femoral endoprosthesis for oncological indications: analysis of variables relating to the patient and the surgical technique.

AIMS: Instability of the hip is the most common mode of failure after reconstruction with a proximal femoral arthroplasty (PFA) using an endoprosthesis after excision of a tumour. Small studies report improved stability with capsular repair of the hip and other techniques, but these have not been investigated in a large series of patients. The aim of this study was to evaluate variables associated with the patient and the operation that affect post-operative stability. We hypothesised an association between capsular repair and stability. PATIENTS AND METHODS: In a retrospective cohort study, we identified 527 adult patients who were treated with a PFA for tumours. Our data included demographics, the pathological diagnosis, the amount of resection of the abductor muscles, the techniques of reconstruction and the characteristics of the implant. We used regression analysis to compare patients with and without post-operative instability. RESULTS: A total of 20 patients out of 527 (4%) had instability which presented at a mean of 35 days (3 to 131) post-operatively. Capsular repair was not associated with a reduced rate of instability. Bivariate analysis showed that a posterolateral surgical approach (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.02 to 0.86) and the type of implant (p = 0.046) had a significant association with reduced instability; age > 60 years predicted instability (OR 3.17, 95% CI 1.00 to 9.98). Multivariate analysis showed age > 60 years (OR 5.09, 95% CI 1.23 to 21.07), female gender (OR 1.73, 95% CI 1.04 to 2.89), a malignant primary bone tumour (OR 2.04, 95% CI 1.06 to 3.95), and benign condition (OR 5.56, 95% CI 1.35 to 22.90), but not metastatic disease or soft-tissue tumours, predicted instability, while a posterolateral approach (OR 0.09, 95% CI 0.01 to 0.53) was protective against instability. No instability occurred when a synthetic graft was used in 70 patients. CONCLUSION: Stability of the hip after PFA is influenced by variables associated with the patient, the pathology, the surgical technique and the implant. We did not find an association between capsular repair and improved stability. Extension of the tumour often dictates surgical technique; however, our results indicate that PFA using a posterolateral approach with a hemiarthroplasty and synthetic augment for soft-tissue repair confers the lowest risk of instability. Patients who are elderly, female, or with a primary benign or malignant bone tumour should be counselled about an increased risk of instability. Cite this article: Bone Joint J 2017;99-B:531-7.

Complete local tumor control after curettage of chondroblastoma-a retrospective analysis.

BACKGROUND: Chondroblastoma is an uncommon benign bone tumor with an incidence of 1 to 2% among all primary bone tumors. In the past, treatment for chondroblastoma has been highly variable leading to different rates of recurrences. Therefore we aimed to determine: (1) the rate of recurrence, (2) the complication rate, (3) and functional outcome after intralesional curettage of chondroblastoma. HYPOTHESES: Intralesional curettage with high speed burring and packing can avoid local recurrences. PATIENTS AND METHODS: Experiences of 22 patients with chondroblastoma of the bone were retrospectively reviewed. The patient group consisted of 16 men; 6 women; mean age 24years (range; 12-58years) affecting in 15 the lower- (68%) and in seven the upper extremity (32%). RESULTS: There was no local recurrence or malignant transformation. All patients underwent intralesional curettage, followed by defect filling presenting in 19 patients (87%) excellent clinical and oncological results (mean MSTS 98.9). Complications were seen in two patients. Pain was the main revealing symptom of the chondroblastoma (n=16, 73%). Mean follow-up of all patients was 114months (range, 25 to 480months). DISCUSSION: Aggressive curettage and packing provided excellent local tumor control and functional results in our patients with chondroblastoma. Malignant transformation is extremely rare, however, present in literature but was not seen in any of our patients. LEVEL OF EVIDENCE: Level IV, retrospective study.

Review of the outcomes of complex acetabular reconstructions using a stemmed acetabular pedestal component.

AIM: Until now, there has been no consensus as to whether stemmed acetabular components are appropriate for use in patients undergoing revision total hip arthroplasty (THA) who have major acetabular defects or pelvic discontinuity. We wished to address this deficiency in the literature. PATIENTS AND METHODS: We carried out a retrospective study of 35 patients (six men and 29 women) with a mean age of 68 years (37 to 87), with major acetabular defects who underwent revision THA between 2000 and 2012. RESULTS: At a mean follow-up of 63 months (24 to 141), a total of 15 patients (43%) had required at least one further operation. Six implants (17%) loosened aseptically, four (11%) were further revised for infection and two (6%) for technical failure. By taking revision for any reason as the endpoint, the rate of survival of the implant was 61% after five years; by taking revision for aseptic loosening as the end point, it was 78%. The cumulative five-year survival for aseptic loosening was 94% in patients without pelvic discontinuity, and 56% in those with pelvic discontinuity. CONCLUSION: These results indicate a significantly worse survival in patients with pelvic discontinuity (p = 0.020) and we advise caution in the use of the pedestal component in patients with major acetabular defects and pelvic discontinuity who require revision THA. As a result of these findings we have stopped using this implant and prefer to use particulate bone grafts protected with an anti-protrusion cage and posterior column plate fixation, if necessary. TAKE HOME MESSAGE: Based on these poor results, we advise caution if using the pedestal component in patients with major acetabular defects with the presence of a pelvic discontinuity. Cite this article: Bone Joint J 2016;98-B:772-9.

Long-term outcome following treatment of Adamantinoma and Osteofibrous dysplasia of long bones.

INTRODUCTION: Adamantinoma (AD) is an ultimately rare, low-grade malignant bone tumor. In most cases it occurs in the tibia of young adults. Osteofibrous dysplasia (OFD) is a rare, benign, lesion that is typically seen in children. Histopathology, ultrastructure, and cytogenetics indicate that these lesions are closely related. Yet, etiology remains a matter of debate. Local recurrence rates are high for both entities as published in literature and long-term outcomes are scarce, due to the rarity of the disease. HYPOTHESIS: AD should be treated by En-Bloc resection while ODF can be treated by curettage or by observation. Consequently, the aim of the present study was to answer following questions: Were local recurrence rates of both entities different based on a retrospective review within a tertiary referral center for orthopedic oncology? MATERIAL AND METHODS: In a retrospective cohort study, 10 patients with AD and 5 patients with OFD (including 1 patient with OFD-like-AD) were reviewed. Primary surgeries for patients with AD were: En-bloc resection in 7, curettage in 2 and amputation in 1. In the OFD group, only 2 patients underwent surgery by curettage. Mean follow-up was 16 years (range: 2-47 years). Nine patients had a minimum follow-up of 10 years (mean: 23 years; range: 10-47 years). RESULTS: Four patients with AD (40%) and 2 patients with OFD (40%) - all of them following surgical removal - suffered from local recurrence. In the "En bloc" resection group of AD, there were 2 LR (29%). All patients of both groups treated with curettage showed LR. One patient with AD had metastasis at time of diagnosis and died of disease. Another patient with AD was diagnosed with metastasis 67 months after surgery and was still alive with disease at latest follow-up (77 month). DISCUSSION: The overall prognosis of AD and OFD is good, yet local recurrence rates are high, irrespective of surgical strategy. While an internationally standardized treatment regime is still missing, a more radical surgical approach should be considered, especially when treating AD. LEVEL OF EVIDENCE: Retrospective study; Level IV.

Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF.

OBJECTIVE: Vascular endothelial growth factor (VEGF) induces the release of nitric oxide (NO) from endothelial cells. There is also limited data suggesting that NO may enhance VEGF generation. METHODS: To further investigate this interaction, we examined the effect of exogenous and endogenous NO on the synthesis of VEGF by rat and human vascular smooth muscle cells (VSMC) by exposing cells to exogenous NO donors, or to genetic augmentation of eNOS or iNOS. RESULTS: NO-donors potentiated by 2-fold the generation of VEGF protein by rat or human VSMC. Similarly, rat or human VSMC transiently transfected with plasmid DNA encoding eNOS or iNOS, synthesized up to 3-fold more VEGF than those transfected with control plasmid DNA, an effect which was reversed after treatment with the NOS antagonist L-NAME. Rat VSMC stably transfected with pKeNOS plasmid, constitutively produced NO and released high concentrations of VEGF. In these cells, L-NAME significantly reduced NO synthesis and decreased VEGF generation. The VEGF protein produced by NOS-transfected VSMC was biologically active, as conditioned media harvested from these cells increased endothelial cell proliferation. CONCLUSION: These studies reveal that NO derived from NO-donors or generated by NOS within the cells, upregulates the synthesis of VEGF in vascular smooth muscle cells. Administration of NO donors, or augmentation of endogenous NO synthesis, may be an alternative approach in therapeutic angiogenesis.

Extendible Prostheses for Children After Resection of Primary Malignant Bone Tumor: Twenty-seven Years of Experience.

BACKGROUND: Endoprosthetic replacement in children following resection of a malignant bone tumor still is controversial because of the high number of reoperations. The aim of this study was to evaluate the long-term outcome with respect to limb-lengthening potential, satisfaction rate, and complications after implantation of extendible devices. METHODS: Seventy-one patients with a sarcoma in an extremity who had been followed for more than twenty-four months (mean, 131.6 months; range, 27.2 to 281.8 months) after tumor resection and prosthetic reconstruction with an extendible device were analyzed. The mean age at the time of the operation was ten years (range, four to sixteen years). The complication-free survival rate was evaluated with competing-risk analysis. Clinical outcomes and complications were rated with use of the Musculoskeletal Tumor Society (MSTS) score and a failure mode classification for segmental tumor endoprostheses, respectively. RESULTS: Twelve of seventy-one patients died of their disease. The overall MSTS score averaged 87.8% (range, 23.3% to 100%). The most common mode of failure was soft-tissue failure (46%), followed by structural failure (28%), infection (17%), and aseptic loosening (8%); only 2% of the children had local recurrence. An average of 4.4 lengthening operations per patient were required for an average limb elongation of 70.8 mm (range, 0 to 224 mm). An average of 2.5 operations (range, zero to eleven) per patient were performed for complications. CONCLUSIONS: Although limb lengthening with an extendible endoprosthesis seems to be effective, many children have related complications. These data will be a source of preoperative information for children and parents, and will provide a benchmark for further clinical improvements.

Delivery of high dose VEGF plasmid using fibrin carrier does not influence its angiogenic potency.

Delivery of DNA mixed with a degradable matrix carrier was supposed to improve transgene expression. Using a rabbit hind-limb ischemia model, we tested the angiogenic potency of plasmid encoding human vascular endothelial growth factor (pSG5-VEGF165) entrapped in fibrin sealant. Animals were injected intramuscularly with 500 microg of pSG5-VEGF165 or control plasmid, dissolved in saline (PBS) or fibrin glue. After 14 days, presence of delivered constructs and expression of transgene was confirmed in injected muscles of all animals. There were no significant differences in the levels of human VEGF mRNA and protein between VEGF-PBS and VEGF-fibrin groups (Mann-Whitney test). Accordingly, pSG5-VEGF165 regardless of the way of delivery, induced similar increases in capillary density within treated muscles (ANOVA). Control plasmid did not show any effects. In conclusion, injection of pSG5-VEGF165 into ischemic adductor muscle leads to synthesis of human VEGF and increases the number of capillaries. Fibrin carrier does not influence its angiogenic potential.