The microbial profile of infected endoprosthetic reconstructions after wide excision for patients with musculoskeletal tumors: A call for pathogen-based practices.

BACKGROUND AND OBJECTIVES: Periprosthetic infection is a devastating complication following endoprosthetic reconstruction. This study utilized a large database of endoprostheses to describe the incidence, risk factors, and microbial profile of such infections to better catalogue and understand these catastrophic events. METHODS: A retrospective review of endoprosthetic reconstructions for an oncologic indication from January 1, 1981 to December 31, 2020 was performed. Demographic, oncologic, procedural and outcome data was analyzed. Multivariable logistic regression was used to identify potential risk factors for infection with significance defined as p < 0.05. RESULTS: Forty four out of 712 (6.2%) reconstructions resulted in infection at a mean time of 39.9 ± 44.5 months. Revision surgery (odds ratio [OR] 6.14, p < 0.001) or having a postoperative wound complication (OR 7.67, p < 0.001) were significantly associated with infection. Staphylococcus aureus and Staphylococcus epidermidis were the most commonly cultured organisms at a rate of 34.1% (15/44) and 22.7% (10/44), respectively. Ten infections resulted in amputation; five due to antimicrobial-resistant infections and three due to polymicrobial infections. CONCLUSION: Understanding the microbial profile of patients undergoing endoprosthetic reconstruction is paramount. This study demonstrates a relatively high rate of polymicrobial and antibiotic-resistant infections that portend worse outcomes, thus suggesting that pathogen-specific infectious practices may be warranted. LEVEL OF EVIDENCE: Retrospective cohort study, level III.

Proximal Femur Replacements for an Oncologic Indication Offer a Durable Endoprosthetic Reconstruction Option: A 40-year Experience.

BACKGROUND: Proximal femur replacements (PFRs) are an effective surgical option to treat primary and metastatic tumors causing large bony defects in the proximal femur. Given the relative rarity of these indications, current studies on PFR for oncologic indications are generally limited by patient volume or relatively short-term follow-up. Because recent advances in systemic therapy have improved the prognosis of patients who undergo limb salvage surgery for musculoskeletal tumors, data on the long-term durability of endoprosthetic reconstructions have become increasingly important. QUESTIONS/PURPOSES: (1) How does the long-term survival of cemented bipolar PFRs compare with patient survival in patients who underwent PFR for benign, aggressive, and metastatic tumors? (2) What are common reasons for revisions of primary PFRs? (3) Which factors are associated with survival of primary PFRs? (4) What is the survivorship free from conversion of bipolar PFRs to THA? METHODS: Between January 1, 1980, and December 31, 2020, we treated 812 patients with an endoprosthetic reconstruction for an oncologic indication. All patients who underwent a primary PFR for an oncologic indication were included in this study. The study cohort consisted of 122 patients receiving a primary PFR. Eighteen patients did not reach a censored endpoint such as death, revision, or amputation within 2 years. Thirty-three patients died within 2 years of their surgery. Of the 122 patients with primary PFRs, 39 did not reach a censored endpoint and have not been seen within the past 5 years. However, the mean follow-up time for these patients was longer than 10 years. The Social Security Death Index was queried to identify any patients who may have died but might not have been captured by our database To allow for adequate follow-up, endoprosthetic reconstructions performed after December 31, 2020 were excluded. The mean age at the time of the index surgery was 48 ± 22 years. The mean follow-up time of surviving patients was 7 ± 8 years. All PFRs were performed using a bipolar hemiarthroplasty with a cemented stem, and all implants were considered comparable. Demographic, oncologic, procedural, and outcome data including prosthesis survival, patient survival, complication rates, and rates of conversion to THA were analyzed. Patient, prosthesis, and limb salvage survival rates were generated, with implant revision as the endpoint and death as a competing risk. Statistical significance was defined as p < 0.05. RESULTS: Generally, patients with benign or low-grade (Stage I) disease outlived their implants (100% patient survival through 30 years; p = 0.02), whereas the opposite was true in patients with high-grade, localized Stage II disease (64% patient survival at 5 years [95% CI 49% to 76%]; p = 0.001) or widespread Stage III metastatic disease (6.2% patient survival at 5 years [95% CI 0.5% to 24%]; p < 0.001). Primary PFR implant survival at 5, 10, 20, and 30 years was 97% (95% CI 90% to 99%), 81% (95% CI 67% to 90%), 69% (95% CI 46% to 84%), and 51% (95% CI 24% to 73%), respectively. Eight percent (10 of 122) of primary PFRs were revised for any reason. The most common causes of revision were aseptic loosening (3% [four of 122]), infection (3% [three of 122]), breakage of the implant (2% [two of 122]), and tumor progression (1% [one of 122]). Follow-up time was the only factor that was associated with revision of primary PFRs. Neither segment length nor stem length were associated with revision of primary. Six percent (seven of 122) of PFRs were converted to THA at a mean 15 ± 8 years from the index procedure. Survivorship free from conversion to THA (accounting for death as a competing risk) was 94% (95% CI 85% to 99%), 86% (95% CI 68% to 94%). and 77% (95% CI 51% to 91%) at 10, 20, and 30 years, respectively. CONCLUSION: Cemented bipolar PFRs for an oncologic indication are a relatively durable reconstruction technique. Given the relative longevity and efficacy of PFRs demonstrated in our study, especially in patients with high-grade or metastatic disease where implant survival until all-cause revision was longer than patient survival, surgeons should continue to seriously consider PFRs in appropriate patients. The relative rarity of these reconstructions limits the number of patients in this study as well as in current research; thus, further multi-institutional collaborations are needed to provide the most accurate prognostic data for our patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

What Is the Long-term Survivorship of Primary and Revision Cemented Distal Femoral Replacements for Limb Salvage of Patients With Sarcoma?

BACKGROUND: Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been in common use for decades. Although multiple studies have reported the survivorship of primary endoprostheses, implant survivorship after revision surgery is less well established. Given that earlier advances in systemic therapy improved survival of patients with sarcoma, the usage of revision endoprostheses can be expected to increase and, as such, understanding revision implant survivorship will help to inform patient and surgeon expectations. Additionally, as new implants are developed that allow alternative reconstruction options, a normative dataset establishing accurate expectations for revision cemented endoprostheses is a critical benchmark by which to measure progress. QUESTIONS/PURPOSES: (1) What is the implant survivorship free of all-cause revision for primary and revision cemented distal femoral replacements (DFRs) used in the treatment of malignant or benign tumors? (2) What are the most common indications for revision of primary and revision DFRs in an oncology population with mean follow-up of more than 10 years? (3) How does the indication for revision of a primary DFR affect the subsequent risk for and type of revision DFR complication? (4) What patient, tumor, or implant characteristics are associated with improved survivorship free of revision in cemented DFRs used in patients treated initially for primary malignant or benign tumors? METHODS: This was a retrospective, comparative study using our institution's longitudinally-maintained database of 806 cemented endoprostheses starting in 1980 and assessed through December 31, 2018. In all, 365 DFRs were inserted during this time, but 14% (51 of 365) were placed for nonprimary bone tumors and 1% (5 of 365) were cementless reconstructions, leaving 309 cemented DFRs. Seventy-one percent (218 of 309) were primary implants and 29 percent (91 of 309) were revision implants (used to revise a prior DFR in all patients). During this time period, our strong bias was to use cemented stems and, thus, nearly all of our patients had cemented stems. Six percent (13 of 218) of primary DFRs were implanted more than 2 years before the study end; however, they lacked 2 years of follow-up data and, thus, were considered lost to follow-up, leaving 205 implants in the primary DFR analysis group. Only the first revision after primary DFR revision surgery was included in the revision cohort analysis. Thirty-two percent (29 of 91) of revision DFRs were second or more revision patients and were excluded, leaving 62 implants in the revision analysis group. Most patients in both groups were men (57% [117 of 205] for primary and 71% [44 of 62] for revision) who had been diagnosed with osteosarcoma (75% [153 of 205] and 73% [45 of 62] for primary and revision, respectively). The primary cohort had mean age of 26 ± 16 years with a mean follow-up of 136 ± 122 months, and the revision cohort had mean age of 31 ± 13 years (p = 0.02) with 141 ± 101 months of follow-up. Study endpoints included all-cause implant revision and cause-specific revision for soft tissue complications, aseptic loosening, structural complications (defined as periprosthetic or implant fracture), infection, or tumor progression. Planned surgery for implant lengthening procedures was excluded. Implant survivorship free from all-cause revision was calculated using a competing risk (cumulative incidence) estimator with death as a competing risk. A log-rank test using chi-square analysis was used to evaluate the differences in implant survivorship between primary DFRs and first revisions. The cause-specific incidences of implant revision were tabulated for primary and revision DFRs. Cox regression analysis investigated the odds of subsequent all-cause revision surgery for revision cemented DFRs based on the primary implant complication. A binary logistic regression analysis using age, gender, indication for revision, tumor type, infection, perioperative chemotherapy, and radiation was performed to identify factors associated with a second DFR reoperation. Relative effect sizes are reported as ORs. RESULTS: The revision DFR cohort had a shorter mean survival to all-cause revision than the primary cohort (mean 10 years [95% CI 7 to 12] versus 18 years [95% CI 15 to 20]; p < 0.001). The most common complications necessitating revision for revision implants were periprosthetic or implant fracture in 37% (23 of 62) and aseptic loosening in 15% (9 of 62), and the type of primary implant complication was not associated with risk of subsequent all-cause revision surgery for revision implants. Stem diameter less than 15 mm was associated with repeat all-cause revision in cemented revision DFRs after controlling for resection length, stem length, implant fabrication (custom or modular), and presence of a porous collar (OR 4 [95% CI 1 to 17]; p = 0.03). No other parameters that we explored, including patient age, gender, chemoradiation history, or primary tumor diagnosis, were associated with repeat revision surgery. CONCLUSION: Understanding modifiable factors that can improve revision DFR survival is critical to achieving long-term limb salvage for patients with tumors around the knee. Our data suggest that utilizing implants with the largest possible stems-or at a minimum increasing the stem size over the primary implant-is important to revision cemented DFR survivorship and is an important part of our revision practice. Improving revision implants' resistance to aseptic loosening through designs that resist torsion (a common mode of cemented fixation failure)-such as with the use of custom cross-pin fabrication-may be one method to improve survivorship. Another will be improved implant metallurgy that is resistant to fatigue fracture. Next steps may include understanding the optimal ratio of femoral diaphyseal width to implant diameter in patients where anatomic constraints preclude the insertion of cemented stems 15 mm or more in diameter. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Is High-dose Radiation Therapy Associated With Early Revision Due to Aseptic Loosening in Patients With a Sarcoma of the Lower Extremities Reconstructed With a Cemented Endoprosthesis?

BACKGROUND: The durability of endoprostheses after limb salvage surgery is influenced by surgical factors (resection length, implant location, and residual bone quality), implant design (modular versus custom design, rotating versus fixed hinge, coating, collars, and the use of cross pins), and host factors (patient's immune status, activity levels, and age). In general, radiation therapy increases the risk of fractures, infection, delayed wound healing, and impaired osseointegration. Several studies have shown exposure to radiation to be associated with higher endoprosthesis revision rates and higher periprosthetic infection rates, but results are inconsistent. Although radiation therapy is not routinely used in the treatment of many bone sarcomas in current practice, it is still used in high doses after resection and prosthetic reconstruction in patients who have Ewing sarcoma with close or positive margins and in patients with soft tissue sarcoma. It is also used in varying doses after prosthetic reconstruction in patients with myeloma or bone metastasis after resection of periarticular destructive tumors. These patients may be at an increased risk of complications due to their radiation exposure, but this is a difficult question to study given the rarity of these diagnoses and poor overall survival of these patients. We therefore leveraged a large, longitudinally collected, 40-year endoprosthesis database that included patients who received radiation to the extremity for many bone and soft tissue sarcomas to investigate the association between preoperative or postoperative radiation therapy and endoprosthesis survival. QUESTIONS/PURPOSES: (1) Is receiving preoperative or postoperative radiation therapy in low or high doses for the treatment of bone or soft tissue malignancy of the lower extremities associated with decreased implant survivorship free from amputation or revision due to any cause? (2) Is receiving preoperative or postoperative radiation therapy in low or high doses for the treatment of bone or soft tissue malignancy of the lower extremities associated with decreased implant survivorship free from revision specifically due to aseptic loosening? (3) Is receiving preoperative or postoperative radiation therapy for the treatment of Ewing sarcoma of the femur specifically associated with decreased implant survivorship free from revision specifically due to aseptic loosening? METHODS: This was a retrospective, comparative study using our institution's database of 822 endoprostheses. Between 1980 and 2019, we treated 541 patients with primary cemented endoprostheses of the extremities. Of those patients, 8% (45 of 541) were excluded due to unknown radiation status, 3% (17 of 541) because of prior failed allograft, 15% (83 of 541) due to metastatic disease from a carcinoma, 1% (6 of 541) due to a nononcologic diagnosis, 4% (20 of 541) due to benign tumor diagnosis, 16% (87 of 541) due to upper extremity tumor location, 9% (49 of 541) due to not receiving chemotherapy, and 3% (14 of 541) due to expandable prostheses. Of the remaining 220 patients, 6% (13) were considered missing because they did not have 2 years of follow-up and did not reach a study endpoint. No patients had surgery within the last 2 years of the study end date. In all, 207 patients met inclusion criteria and were eligible for analysis. Patients who had received radiation to the lower extremities at any point in their treatment course were included in the radiation group and were compared with patients who did not receive radiation. For patients where radiation dose was available, the radiation group was subdivided into a low-dose (≤ 3000 cGy) and high-dose (> 3000 cGy) group. Revision surgery was defined as any surgery necessitating removal or replacement of the tibial or femoral stem. The complications necessitating revision or amputation were poor wound healing, aseptic loosening, implant breakage, deep infection, and tumor progression. The primary outcome of interest was implant survival free from revision or amputation due to any cause. The secondary outcome of interest was implant survival free from revision or amputation specifically due to aseptic loosening. The Kaplan-Meier survivorship curves were generated with implant survival free from revision or amputation as the endpoint and patient death as a competing risk. A log-rank test was used to identify differences in survivorship between the patients who received radiation and those who did not. Multivariate regression was used to identify factors associated with decreased implant survival. An odds ratio was used to determine relative effect size among the factors associated with decreased implant survival. RESULTS: The mean implant survival time for patients who did not receive radiation was 18.3 years (95% confidence interval [CI] 15.4 to 21.3) whereas the mean implant survival time for patients who received low- and high-dose radiation were 19.1 years (95% CI 14.5 to 23.7; p = 0.59) and 13.8 years (95% CI 8.2 to 19.5; p = 0.65), respectively. The mean implant survival free from revision for aseptic loosening for patients who did not receive radiation was 27.1 years (95% CI 24.1 to 30.1) whereas the mean implant survival for patients who received low- and high-dose radiation were 24.1 years (95% CI 19.1 to 29.1; p = 0.34) and 16.4 years (95% CI 10.6 to 22.2; p = 0.01), respectively. Patients who received high-dose radiation had decreased 5-year implant survivorship free from amputation or revision due to aseptic loosening (73% [95% CI 44% to 89%]) compared with patients who did not receive radiation (95% [95% CI 90% to 99%]; p = 0.01). For patients treated for Ewing sarcoma of the femur, the 5-year implant survival free from amputation or revision due to aseptic loosening for patients who did not receive radiation (100% [95% CI 100% to 100%]) was no different compared with patients who received radiation (71% [95% CI 35% to 90%]; p = 0.56). CONCLUSION: The results of this study may apply to scenarios where radiation is used, such as Ewing sarcoma with positive margins or local recurrence and after prosthetic reconstruction in patients with myeloma or bone metastasis after resection of periarticular destructive tumors. Surgeons may consider closer monitoring for early clinical and radiographic signs of aseptic loosening in patients who received high-dose radiation. These patients may also benefit from constructs that have increased resistance to aseptic loosening such as cross-pin or side plate fixation. The association between radiation and aseptic loosening should be further studied with larger studies with homogeneity in tumor diagnosis and prosthesis. The dose-dependent relationship between radiation and bone-related complications may also benefit from controlled, laboratory-based biomechanical studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Gait outcomes following proximal tibial tumor resection and endoprosthetic reconstruction.

BACKGROUND: Despite the proximal tibia being a common site of primary malignant bone tumors, there is limited information about gait function following proximal tibial tumor resection and endoprosthetic reconstruction (PTR). RESEARCH QUESTION: What is the impact of PTR on gait and quality of life? METHODS: This was a cross-sectional study of patients ≥18 years old who were ≥2 years post-PTR compared to a control group of similar age and sex distribution. Eighteen participants (9 PTR, 9 Control) were recruited. Gait spatial-temporal data, joint kinematics and kinetics were collected at preferred and fast walking speeds. Community walking cadence, health-related quality of life (SF-36) and knee joint torque were assessed. Comparisons were performed using one-way ANOVAs with Bonferroni corrections for multiple comparisons. Nonparametric tests were used for data not normally distributed. RESULTS: Mean age was 31 years for each group (PTR range = 18-42 yrs, Control range = 18-44 yrs). Compared to both control and nonsurgical limbs, the surgical limb exhibited significantly decreased % single limb support time, reduced heel rise during terminal stance and an absence of normally occurring knee flexion angles, extensor moments and power generation during initial double limb support. Additionally, a reduced peak plantar flexor moment was found for the surgical as compared to the control limb. The number of gait abnormalities increased during fast walking. Significantly reduced surgical knee extensor torque on isokinetic testing and weakness of the knee and ankle on clinical examination support gait findings. During community walking, the number of low frequency strides was an average of 5.3 % greater for the PTR group (p <  0.05). Norm-based PTR group SF-36 component scores were within normal values (53.4 physical, 56.5 mental). SIGNIFICANCE: Gait abnormalities were consistent with ankle muscle resection and transposition and knee extensor mechanism disruption. Despite these deficits, walking speed and quality of life were relatively normal.

Metaphyseal Stem Tip Location is a Risk Factor for Aseptic Loosening of Cemented Distal Femoral Replacements.

BACKGROUND: The objective of this study was to describe the incidence of aseptic loosening (AL) of cemented stem distal femoral replacements (DFR) and to identify modifiable risk factors for its development. METHODS: A retrospective review was performed of 245 consecutive primary, cemented stem DFRs implanted at a single institution over a 40-year period. The primary outcome was revision surgery for AL. A multivariate analysis was performed to identify risk factors for AL. Radiographs were reviewed to identify stem tip location, which was defined as diaphyseal or metaphyseal. Implant survival to AL was compared using Kaplan-Meier analysis. RESULTS: AL and structural failure were the most common causes of implant failure (incidence 11.8%, 29/245). Younger age (P = .002), male sex (P = .01), longer resection length (P = .04), and nonmodular implants (P = .002) were all significantly associated with AL. After 1:1 matching, stem tip location in metaphyseal bone was independently associated with AL (P = .04). 36% (9/25) of implants that loosened had a stem tip located in the metaphysis vs only 8% (2/25) of implants that did not fail. 30-year survival to AL was lower for implants with a metaphyseal stem tip than implants with a diaphyseal stem tip (22.7% vs 47.6%; P = .11). CONCLUSION: A stem tip location in metaphyseal bone is associated with diminished survival to AL. When templating before DFR, stem tip location can assist in identifying high-risk reconstructions that may benefit from alternative or supplemental fixation techniques to prevent the development of AL.

Long term outcomes of total humeral replacement for oncological reconstructions: A single institution experience.

BACKGROUND: There is a paucity of data on long-term survivorship and outcomes for total humerus replacements (THR) with only two series reporting 10-year survival. PATIENTS AND METHODS: A review of 769 consecutive, prospectively collected endoprosthetic reconstructions for oncological diagnoses at a single-center between 1980 and 2019 was performed. Patients with THRs were isolated and analyzed for outcomes, complications, and modes of failure. RESULTS: Eighteen patients with 20 THR implants were identified. The median follow-up for surviving patients was 148 months (interquartile range [IQR] = 74-194) and 60 months (IQR = 17-155 months) for all patients. Two prostheses required revision for failure, both for symptomatic shoulder dislocation. There were three local recurrences. Revision-free survival at 5, 10, and 15 years was 100%, 86% and 86%, respectively. There were no cases of ulnar component failure, radial nerve palsy, or periprosthetic infection. CONCLUSIONS: THR prosthesis survivorship is comparable to the previous series, with a longer follow-up than has previously been reported. Symptomatic shoulder instability was common (25%), and was the only cause of revision. Reverse total shoulder could be an important way to address this in the future. Local recurrence rates were high, as has been reported elsewhere for THR.

Long-term follow-up of all-polyethylene tibial components when used for oncological endoprosthetic reconstruction.

AIMS: We aimed to examine the long-term mechanical survivorship, describe the modes of all-cause failure, and identify risk factors for mechanical failure of all-polyethylene tibial components in endoprosthetic reconstruction. METHODS: This is a retrospective database review of consecutive endoprosthetic reconstructions performed for oncological indications between 1980 and 2019. Patients with all-polyethylene tibial components were isolated and analyzed for revision for mechanical failure. Outcomes included survival of the all-polyethylene tibial component, revision surgery categorized according to the Henderson Failure Mode Classification, and complications and functional outcome, as assessed by the Musculoskeletal Tumor Society (MSTS) score at the final follow-up. RESULTS: A total of 278 patients were identified with 289 all-polyethylene tibial components. Mechanical survival was 98.4%, 91.1%, and 85.2% at five, ten and 15 years, respectively. A total of 15 mechanical failures were identified at the final follow-up. Of the 13 all-polyethylene tibial components used for revision of a previous tibial component, five (38.5%) failed mechanically. Younger patients (< 18 years vs > 18 years; p = 0.005) and those used as revision components (p < 0.001) had significantly increased rates of failure. Multivariate logistic regression modelling showed revision status to be a positive risk factor for failure (odds ratio (OR) 19.498, 95% confidence interval (CI) 4.598 to 82.676) and increasing age was a negative risk factor for failure (OR 0.927, 95% CI 0.872 to 0.987). Age-stratified risk analysis showed that age > 24 years was no longer a statistically significant risk factor for failure. The final mean MSTS score for all patients was 89% (8.5% to 100.0%). CONCLUSION: The long-term mechanical survivorship of all-polyethylene tibial components when used for tumour endoprostheses was excellent. Tumour surgeons should consider using these components for their durability and the secondary benefits of reduced cost and ease of removal and revision. However, caution should be taken when using all-polyethylene tibial components in the revision setting as a significantly higher rate of mechanical failure was seen in this group of patients. Cite this article: Bone Joint J. 2020;102-B(2):170-176.

Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas.

OBJECTIVES: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/ß 10] 36.4 Gy [α/ß 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P<0.05. RESULTS: Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS. CONCLUSIONS: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.

Long-term outcomes of cement in cement technique for revision endoprosthesis surgery.

BACKGROUND AND OBJECTIVE: Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been a standard-of-care option for decades. With increased patient survival, the incidence of failed endoprostheses requiring revision surgery has increased. Revision of cemented endoprotheses by cementing into the existing cement mantle (CiC) is technically demanding. METHODS: This is a retrospective review of our endoprosthesis database of 512 consecutive cemented endoprosthetic reconstructions performed for oncologic diagnoses between 1980 and 2014. A total of 54 implants (mean patient age 32 years, range 13-81) were revised with a CiC technique. Outcomes evaluated were prosthesis survival, revision surgery categorized according to the Henderson Failure Mode Classification, complications, and functional scores. RESULTS: Fifteen-year Kaplan-Meier survival rate was 34% for initial revision and 39% for subsequent revision implants. Mean revised Musculoskeletal Tumor Society (MSTS) Score was 27 at latest follow-up. Infection rate was 2%, 9%, and 13% for primary endoprostheses, initial revisions, and subsequent revisions, respectively. Limb salvage rate was 87%. CONCLUSIONS: At long-term follow up, endoprostheses revised with the CiC technique showed consistent 15-year survival from initial (34%) to subsequent (39%) revision. Despite a relatively high failure rate, these results are encouraging and demonstrate that this is a conservative, repeatable technique.

What are the functional outcomes of endoprosthestic reconstructions after tumor resection?

BACKGROUND: The majority of published functional outcome data for tumor megaprostheses comes in the form of subjective functional outcome scores. Sparse objective data exist demonstrating functional results, activity levels, and efficiency of gait after endoprosthetic reconstruction in patients treated for orthopaedic tumors. Patients embarking on massive surgical operations, often in the setting of debilitating medical therapies, face mortality and a myriad of unknowns. Objective functional outcomes provide patients with reasonable expectations and a means to envision life after treatment. Objective outcomes also provide a means for surgeons to compare techniques, rehabilitation protocols, and implants. QUESTIONS/PURPOSES: We asked the following questions: (1) What is the efficiency of gait (ie, oxygen consumption) at final recovery from endoprosthetic reconstruction for oncologic resections? (2) What is the knee strength after lower extremity endoprosthetic reconstruction as compared with the contralateral limb? (3) How active are patients with tumor megaprostheses at home and in the community? METHODS: Sixty-nine patients with endoprosthetic reconstructions for primary lower extremity bone sarcoma met inclusion criteria and were invited by mailing to undergo oxygen cost study and strength testing. Twenty-four patients (seven proximal femoral replacements, nine distal femoral replacements, and eight proximal tibia replacements) underwent evaluation in the gait laboratory at a mean of 13.2 years after their reconstruction. All patients were then asked to wear step activity monitors at home and in the community for 7 consecutive days. RESULTS: Median O2 consumption (in mL/kg/m) among the endoprothesis groups was not different from the control patients with the numbers available (proximal femoral replacement 0.17, distal femoral replacement 0.16, proximal tibia replacement 0.18, control 0.15, p = 0.21). With the numbers available, there was no difference in walking speed as compared with the control group (proximal femoral replacement 1.20 m/s, distal femoral replacement 1.27 m/s, proximal tibia replacement 1.12 m/s, control 1.27 m/s, p = 0.08). Patients with proximal tibia replacements had reduced knee extension and flexion strength compared with patients in other reconstruction groups (84% reduction in extension versus those with proximal femoral replacements, 35%, and distal femoral replacement, 53%, p = 0.001, and 43% reduction in flexion versus proximal femoral replacement, 11%, distal femoral replacement, 2%, p = 0.006). With the numbers available, mean strides per day were not different among the reconstruction groups (proximal femoral replacement = 4709 strides/day [3094-6696], distal femoral replacement = 2854 [2461-6015], and proximal tibia replacement = 4411 [3093-6215], p = 0.53). CONCLUSIONS: Although knee strength was reduced in patients with proximal tibia replacements compared with femoral reconstructions, all groups had an efficient gait and were active at home and in the community at a mean of 13.2 years after surgery. Despite the magnitude of these surgeries, these patients are similarly active as patients after standard total hip arthroplasty. These findings provide objective data from which patients undergoing tumor megaprosthesis reconstructions of the lower extremity can reasonably base expectations of efficient gait and active lifestyles outside of the hospital setting. These data may provide hope and long-term goals for patients facing the uncertainty of chemotherapy and surgical treatment. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Endoprosthetic reconstruction after resection of musculoskeletal tumors.

In the literature, long-term survival of endoprosthetic reconstruction varies widely. Few long-term reports analyze both anatomical and disease-specific implant and patient survival. We retrospectively reviewed the results of 489 patients who underwent resection of musculoskeletal tumor and reconstruction using an endoprosthetic device between December 1980 and August 2009. Implants were considered to have failed if the cemented components were revised for any reason, or the major body segment was removed for any reason. Implant survival, limb survival, and patient survival were determined using the Kaplan-Meier method. Sixty-one (12.5%) of the 489 cases were revised at a mean follow-up of 6.6 years (range, 1 month to 27.3 years). Kaplan-Meier analysis revealed overall implant survival of 23.1% at 27 years (95% CI, 5.0% to 100.0%). At 15 years, modular implants outperformed older custom designs (90.8% and 59.6% survival, respectively; P < .05). Complications that led to failure of the limb-salvage effort included local recurrence (21 cases), infection (11), positive surgical margins (3), and intractable pain (1). Thirty-six amputations (7.4%) were performed. There were no cases of amputation performed as a direct outcome of mechanical failure. Endoprosthetic implants provide a reliable, durable method of reconstruction after resection of musculoskeletal tumors.

Image-guided percutaneous core needle biopsy of musculoskeletal tumors in children.

The use of image-guided percutaneous core needle biopsy (PCNB) to obtain tissue diagnosis of musculoskeletal lesions has become the standard of care in adult patients with a success rate of over 80%. Previous reports indicate a similar success rate in diagnosing pediatric solid tumors. In this large study, we analyzed >10 years of data in which PCNB was used for tissue diagnosis of musculoskeletal lesions in children; we evaluated the histopathologic accuracy, anesthetic requirements, and complications of these procedures. In 122 children, tissue diagnosis was successfully obtained in 82% of cases, and there were 0 complications associated with the procedure. There was a significantly higher PCNB diagnostic success rate in malignant lesions (93%). These data suggest that the use of PCNB is a safe and effective means of diagnosing musculoskeletal lesions in children.

Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma.

BACKGROUND: The authors present the long-term follow-up (>25 years) data from 1 of the original prospective, randomized trials that compared adjuvant chemotherapy with expectant management in patients with high-grade, localized osteosarcoma. In addition, the value of pathologic necrosis induced by a single cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease-free and overall survival. METHODS: Fifty-nine patients with high-grade, localized osteosarcoma were enrolled in a prospective trial that was performed between 1981 and 1984 at the University of California-Los Angeles (UCLA). Patients were randomized to receive either adjuvant chemotherapy or observation after surgical resection. Long-term outcomes, follow-up, and pathologic review of all available histologic sections were performed. RESULTS: The 25-year disease-free survival rate was 28% for patients who received adjuvant chemotherapy compared with 15% for the untreated patients (P = .02). The overall survival rate at 25 years was also significantly higher for treated patients versus untreated patients (38% vs 15%; P = .02). Tumor necrosis >90% after a single round of chemotherapy was a statistically significant predictor of overall survival and disease-free survival for patients who received adjuvant therapy (164 months vs 65 months [P = .04] and 141 months vs 14 months [P < .01], respectively). CONCLUSIONS: Patients with high-grade, localized osteosarcoma who received adjuvant chemotherapy after undergoing definitive surgical resection had a statistically significant benefit in disease-free and overall survival that was maintained through 25 years. Tumor necrosis after just 1 cycle of neoadjuvant chemotherapy and radiation was predictive of overall survival and disease-free survival in patients who received adjuvant chemotherapy.

Giant cell tumor of bone: are we stratifying results appropriately?

BACKGROUND: There is no consensus as to which surgical approach to the treatment of giant cell tumor of bone is most appropriate or which patients are at a higher risk for recurrence or metastasis. QUESTIONS/PURPOSES: Therefore, we asked: (1) Are there subsets of patients who are associated with a more recalcitrant disease course? And (2) are surgeons appropriately stratifying patients by identifying risk factors for increased local recurrence and pulmonary metastases? METHODS: We retrospectively reviewed the records of 230 patients with giant cell tumor of bone treated from 1980 to 2010, stratifying them by primary versus recurrent disease and by surgical treatment. From the records, we determined local recurrence, metastatic disease, and complications of treatment. The median follow up was 47 months (range, 0.1-312 months). RESULTS: Overall incidence of local recurrence was 10% and pulmonary metastasis was 2%. When stratified by surgical treatment, the incidence of local recurrence among patients undergoing intralesional curettage (12%) was greater than in those undergoing resection (2%). The incidence of local recurrence among primary tumors, independent of treatment, was 9%, whereas the incidence of local recurrence after treatment of recurrent lesions was 16%. The incidence of pulmonary metastases was similar, regardless of treatment or whether primary or recurrent. CONCLUSIONS: Our observations suggest there are subsets of patients with giant cell tumor of bone who are at higher risk of recurrence and should be clinically followed more closely. This should allow surgeons to provide patients with more informed expectations. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Chronic sclerosing osteomyelitis treated with wide resection and vascularized fibular autograft: a case report.

Treatment recommendations for chronic culture-negative sclerosing osteomyelitis in the pediatric population have largely focused on supportive care, given the typical improvement in symptoms that occurs over time. This case report describes a patient with chronic sclerosing osteomyelitis (CSO) of the humerus who failed a prolonged course of nonoperative management. Definitive treatment consisted of resection of the diseased bone and reconstruction using a vascularized fibular osteocutaneous flap. To our knowledge, this is the first reported case of this technique being utilized specifically for CSO refractory to nonoperative management. At the time of most recent follow-up (35 months), the patient was completely pain-free and off all medication. Physical examination revealed full unrestricted passive and active range of motion. Radiographs at the time of most recent follow-up revealed intact hardware, excellent proximal and distal graft incorporation, and cortical hypertrophy. Vascularized fibular osteocutaneous flap reconstruction following resection is a viable alternative to nonoperative, expectant management for patients with refractory chronic sclerosing osteomyelitis.

How long do endoprosthetic reconstructions for proximal femoral tumors last?

BACKGROUND: As the life expectancy of patients with musculoskeletal tumors improves, long-term studies of endoprosthetic reconstructions are necessary to establish realistic expectations for the implants and compare them to other reconstruction approaches. QUESTIONS/PURPOSES: (1) What is the long-term survival of cemented bipolar proximal femoral replacements? (2) How does prosthesis survival compare to patient survival among patients with Stage I, II, and III disease? (3) Do modular implants outperform custom-built prostheses? (4) Do some proximal femoral replacements require conversion to THA? PATIENTS AND METHODS: We retrospectively reviewed all 86 proximal femoral replacements used for tumor reconstruction from 1982 to 2008. Primary diagnoses were 43 high-grade tumors (IIA/IIB), 20 low-grade tumors (IA/IB or benign), and 23 with metastatic disease. We reviewed prosthesis survival, patient survival, complication rates, functional outcomes, and rates of conversion to THA. RESULTS: Five of 86 patients (5.8%) required revision of the femoral component. Five-, 10-and 20-year implant survivorships were 93%, 84%, and 56%, respectively. All patients with low-grade disease survived; the 5-year survival rate for patients with metastatic disease was 16%; the 5-, 10-, and 20-year survival for IIA/IIB patients was 54%, 50%, and 44%, respectively. Five of 86 patients (5.8%) underwent conversion to THA for groin pain. CONCLUSIONS: Cemented bipolar proximal femoral replacements after tumor resection proved a durable reconstruction technique. The implants outlived patients with metastatic disease and high-grade localized disease while patients with low-grade disease outlived their implants. The survival of modular prostheses was comparable to that of older, one-piece custom designs.

Cemented endoprosthetic reconstruction of the proximal tibia: how long do they last?

BACKGROUND: The few available studies documenting the long-term survival of cemented proximal tibial endoprostheses for musculoskeletal tumors do not differentiate between stem designs or patient diagnosis. There is wide variation in survival rates reported, possibly a result of this heterogeneity in patient population and implant design. QUESTIONS/PURPOSES: We therefore asked: (1) How long do proximal tibial endoprostheses last? (2) What is the typical long-term functional result after proximal tibial replacement? And (3) what are the short- and long-term complications associated with endoprosthetic reconstruction of the proximal tibia, particularly with respect to the soft tissue reconstruction? PATIENTS AND METHODS: We retrospectively reviewed 52 patients with 52 proximal tibial endoprosthetic reconstructions for a tumor-related diagnosis. Kaplan-Meier survivorship analysis was performed using revision of the stemmed components for any reason as an endpoint for implants, and death due to disease progression for patients. Function was assessed using the MSTS scoring system. The minimum followup was 1 month (mean, 96 months: range, 1-284 months; median, 69 months). RESULTS: Using revision of the stemmed components for any reason as an end point, overall prosthesis survival at 5, 10, 15, and 20 years was 94%, 86%, 66%, and 37%, respectively. The 29 modular implants demonstrated a trend toward improved survival compared to the 23 custom-designed components, with a 15-year survivorship of 88% versus 63%. The mean postoperative Musculoskeletal Tumor Society score at most recent followup was 82% of normal function (mean raw score, 24.6; range, 4-29). CONCLUSIONS: Cemented endoprosthetic reconstruction of the proximal tibia provides a reliable method of reconstruction following tumor resection.

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas.

Purpose. The aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods. Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results. Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders (64 +/- 19% versus 29 +/- 30 %, resp.; P = .03). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion. These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.