Survival and failure modes of the Compress® spindle and expandable distal femur endoprosthesis among pediatric patients: A multi-institutional study.

BACKGROUND: Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported. METHODS: We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis. RESULTS: Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years. CONCLUSIONS: There is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study.

OBJECTIVE: To examine the impact of major vascular resection on sarcoma resection outcomes. SUMMARY BACKGROUND DATA: En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described. METHODS: Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival. RESULTS: From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion. CONCLUSIONS: Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

Patterns of Local Recurrence and Risk of Skin Recurrence in Soft Tissue Sarcomas After Surgical Resection.

PURPOSE: Although there is a theoretical risk of skin seeding during surgical resection of soft tissue sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during radiation therapy (RT). However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT. METHODS AND MATERIALS: We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007 and 2021. For patients who developed LR, the depth was evaluated. Progression-free survival and overall survival were analyzed from time of first LR using the Kaplan-Meier method. Cumulative incidence of distant metastasis was calculated with competing risk analysis from date of LR. RESULTS: Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, 5 patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had preoperative RT, 53.3% had postoperative RT, and bolus was used in 46.7%. Surgical margins were close (<1 mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone, and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within the RT field in 13 patients (86.7%). At 1 year after LR, progression-free survival was 70.3%, overall survival was 81.7%, and cumulative incidence of distant metastasis was 5.9%. CONCLUSIONS: Skin recurrences were rare after surgical resection of STSs and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach.

PURPOSE: Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes. EXPERIMENTAL DESIGN: Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model. RESULTS: PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden. CONCLUSIONS: The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.

Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy.

Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets. We discovered three conserved cellular communities or ecotypes associated with underlying genomic alterations and distinct clinical outcomes. We show that one ecotype defined by tumor-associated macrophages and epithelial-like malignant cells predicts response to immune-checkpoint inhibition but not chemotherapy and validate our findings in an independent cohort. Our results may enable identification of patients with soft tissue sarcomas who could benefit from immunotherapy and help develop new therapeutic strategies.

Long-term Outcomes of Diffuse or Recurrent Tenosynovial Giant Cell Tumor Treated with Postoperative External Beam Radiation Therapy.

PURPOSE: Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis. Primary treatment involves surgical resection; however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence. We report and update our institutional experience treating diffuse and recurrent TGCT with postsurgical external beam radiation therapy. METHODS AND MATERIALS: We performed a retrospective chart review of 30 patients with TGCT from 2003 to 2019 treated with radiation therapy. Each patient was evaluated for demographics, radiation treatment parameters, surgical management, complications, and outcome. RESULTS: With mean follow-up of 82 months (range, 3-211), 24 patients (80%) who underwent surgery followed by radiation therapy did not experience any further relapse, and all 30 patients achieved local control (100%) with additional salvage therapy after radiation therapy. The most common site of disease was the knee (n = 22, 73%), followed by the ankle (n = 5, 16%) and the hand (n = 3, 10%). Seven patients (24%) presented at time of initial diagnosis and 23 (76%) presented with recurrent disease after surgical resection, with an average of 2.6 surgical procedures before radiation therapy. After resection, 18 of 30 patients (67%) demonstrated residual TGCT by imaging. The median radiation therapy dose delivered was 36 Gy (range, 34-36 Gy) in 1.8 to 2.5 Gy/fractions for 4 weeks. In the assessment of posttreatment joint function, 26 sites (86%) exhibited excellent or good function, 2 (7%) fair, and 2 poor (7%) as determined by our scoring system. There were no cases of radiation-associated malignancy. CONCLUSIONS: Among patients with diffuse or recurrent TGCT, postsurgical external beam radiation therapy provided excellent local control and good functional status, with minimal treatment-related complications. Postsurgical radiation therapy is a well-tolerated noninvasive treatment that should be considered after maximal cytoreductive resection to prevent disease progression and recurrence.

Development and characterization of new patient-derived xenograft (PDX) models of osteosarcoma with distinct metastatic capacities.

Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology, especially for highly aggressive cancers with a propensity for metastatic spread. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, a large panel of models is needed to fully elucidate key aspects of disease biology and to recapitulate clinically-relevant phenotypes. We describe the development and characterization of osteosarcoma patient-derived xenografts (PDXs) and a panel of PDX-derived cell lines. Matched patient samples, PDXs, and PDX-derived cell lines were comprehensively evaluated using whole genome sequencing and RNA sequencing. PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication (WGD) in a subset of cell lines. These cell line models were heterogeneous in their metastatic capacity and their tissue tropism as observed in both intravenous and orthotopic models. As proof-of-concept study, we used one of these models to test the preclinical effectiveness of a CDK inhibitor on the growth of metastatic tumors in an orthotopic amputation model. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden in this model.

Surgical technique: Methods for removing a Compress® compliant prestress implant.

BACKGROUND: The Compress® device uses a unique design using compressive forces to achieve bone ingrowth on the prosthesis. Because of its design, removal of this device may require special techniques to preserve host bone. DESCRIPTION OF TECHNIQUES: Techniques needed include removal of a small amount of bone to relieve compressive forces, use of a pin extractor and/or Kirschner wires for removal of transfixation pins, and creation of a cortical window in the diaphysis to gain access to bone preventing removal of the anchor plug. METHODS: We retrospectively reviewed the records of 63 patients receiving a Compress® device from 1996 to 2011 and identified 11 patients who underwent subsequent prosthesis removal. The minimum followup was 1 month (average, 20 months; range, 1-80 months). The most common reason for removal was infection (eight patients) and the most common underlying diagnosis was osteosarcoma (five patients). Three patients underwent above-knee amputation, whereas the others (eight patients) had further limb salvage procedures at the time of prosthesis removal. RESULTS: Five patients had additional unplanned surgeries after explantation. Irrigation and débridement of the surgical wound was the most common unplanned procedure followed by latissimus free flap and hip prosthesis dislocation. At the time of followup, all patients were ambulating on either salvaged extremities or prostheses. CONCLUSION: Although removal of the Compress® device presents unique challenges, we describe techniques to address those challenges.

Metastatic Pattern of Truncal and Extremity Leiomyosarcoma: Retrospective Analysis of Predictors, Outcomes, and Detection.

Leiomyosarcomas (LMS) are a heterogenous group of malignant mesenchymal neoplasms with smooth muscle origin and are classified as either non-uterine (NULMS) or uterine (ULMS). Metastatic pattern, prognostic factors, and ideal staging/surveillance studies for truncal and extremity LMS have not been defined. A retrospective analysis of patients diagnosed with histopathology-confirmed truncal or extremity LMS between 2009 and 2019 was conducted. Data collected included demographics, tumor characteristics, staging, surveillance, and survival endpoints. The primary site was defined as: (1) extremity, (2) flank/Pelvis, or (3) chest wall/Spine. We identified 73 patients, 23.3% of which had metastatic LMS at primary diagnosis, while 68.5% developed metastatic disease at any point. The mean metastatic-free survival from primary diagnosis of localized LMS was 3.0 ± 2.8 years. Analysis of prognostic factors revealed that greater age (≥50 years) at initial diagnosis (OR = 3.74, p = 0.0003), higher tumor differentiation scores (OR = 12.09, p = 0.002), and higher tumor necrosis scores (OR = 3.65, p = 0.026) were significantly associated with metastases. Older patients (≥50 years, OR = 4.76, p = 0.017), patients with larger tumors (≥5 cm or ≥10 cm, OR = 2.12, p = 0.02, OR = 1.92, p = 0.029, respectively), higher differentiation scores (OR = 15.92, p = 0.013), and higher necrosis scores (OR = 4.68, p = 0.044) show worse survival outcomes. Analysis of imaging modality during initial staging and during surveillance showed greater tumor detection frequency when PET imaging was employed, compared to CT imaging (p < 0.0001). In conclusion, truncal and peripheral extremity LMS is an aggressive tumor with high metastatic potential and mortality. While there is a significant risk of metastases to lungs, extra-pulmonary tumors are relatively frequent, and broad surveillance may be warranted.

Management of Patients with Newly Diagnosed Desmoid Tumors in a First-Line Setting.

The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0−87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease.

Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors.

PURPOSE: A major component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here, we use single-cell RNA sequencing (scRNA-seq) to investigate cellular interactions in TGCT. EXPERIMENTAL DESIGN: A total of 18,788 single cells from three TGCT and two giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The three TGCTs were additionally analyzed using long-read RNA sequencing. Immunofluorescence and IHC for a range of markers were used to validate and extend the scRNA-seq findings. RESULTS: Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to nonneoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping MAB features between the giant cells in TGCT and GCTB. CONCLUSIONS: The neoplastic cells in TGCT are highly similar to nonneoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the platelet-derived growth factor receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

Curettage and cryosurgery for low-grade cartilage tumors is associated with low recurrence and high function.

BACKGROUND: Chondrosarcomas of bone traditionally have been treated by wide or radical excision, procedures that may result in considerable lifelong disability. Grade 1 chondrosarcomas have little or no metastatic potential and are often difficult to distinguish from painful benign enchondromas. Curettage with adjuvant cryosurgery has been proposed as an alternative therapy for Grade 1 chondrosarcomas given the generally better function after the procedure. However, because it is an intralesional procedure, curettage and cryosurgery may be associated with higher rates of recurrence. QUESTIONS/PURPOSES: We asked whether Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery are associated with low recurrence rates and high functional scores. PATIENTS AND METHODS: We retrospectively reviewed the records of 46 patients with Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery. Forty-one patients had tumors of the long bones. Patients were followed a minimum of 18 months (average, 47.2. months; range, 18-134 months) for evidence of recurrence and for assessment of Musculoskeletal Tumor Society (MSTS) functional score. RESULTS: Two of the 46 patients had recurrences in the original tumor site (4.3% recurrence rate), which subsequently were removed by wide excision, and both patients were confirmed to be disease-free 36 and 30 months, respectively, after the second surgery. The mean MSTS score was 27.2 of 30 points (median, 29 points). CONCLUSIONS: Our observations show curettage with cryosurgery is associated with low recurrence of Grade 1 chondrosarcoma and high functional scores. Curettage with cryosurgery is a reasonable alternative to wide or radical excision as the treatment for Grade 1 chondrosarcomas, and allows for more radical surgery in the event of local recurrence. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University.

BACKGROUND: As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure. METHODS: We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins. RESULTS: 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009). CONCLUSIONS: Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

Genome-Informed Targeted Therapy for Osteosarcoma.

Osteosarcoma is a highly aggressive cancer for which treatment has remained essentially unchanged for more than 30 years. Osteosarcoma is characterized by widespread and recurrent somatic copy-number alterations (SCNA) and structural rearrangements. In contrast, few recurrent point mutations in protein-coding genes have been identified, suggesting that genes within SCNAs are key oncogenic drivers in this disease. SCNAs and structural rearrangements are highly heterogeneous across osteosarcoma cases, suggesting the need for a genome-informed approach to targeted therapy. To identify patient-specific candidate drivers, we used a simple heuristic based on degree and rank order of copy-number amplification (identified by whole-genome sequencing) and changes in gene expression as identified by RNA sequencing. Using patient-derived tumor xenografts, we demonstrate that targeting of patient-specific SCNAs leads to significant decrease in tumor burden, providing a road map for genome-informed treatment of osteosarcoma. SIGNIFICANCE: Osteosarcoma is treated with a chemotherapy regimen established 30 years ago. Although osteosarcoma is genomically complex, we hypothesized that tumor-specific dependencies could be identified within SCNAs. Using patient-derived tumor xenografts, we found a high degree of response for "genome-matched" therapies, demonstrating the utility of a targeted genome-informed approach.This article is highlighted in the In This Issue feature, p. 1.

Extraskeletal osteosarcoma of the hand: the role of marginal excision and adjuvant radiation therapy.

BACKGROUND: Extraskeletal osteosarcoma of the hand is rare, and its optimal modality of local control is not currently known. METHODS: A literature search was performed to identify studies that describe the treatment and outcomes of extraskeletal osteosarcoma. A second literature search was performed to identify studies that describe the treatment and outcomes of extraskeletal osteosarcoma of the hand specifically. RESULTS: The role of adjuvant radiation for extraskeletal osteosarcoma is not well defined. All cases in the literature describing treatment of extraskeletal osteosarcoma of the hand utilized amputation, and none of the patients described received radiation therapy. However, there are multiple reports showing excellent local control, minimal toxicity, and superior functional outcome with limb conservation and radiation rather than amputation of the hand in pediatric and adult soft tissue sarcoma. CONCLUSION: For extraskeletal osteosarcoma of the hand, we recommend a treatment approach with the goal of preservation of form and function using limb-sparing surgery and planned postoperative radiation.

Intercalary tibial allografts following tumor resection: the role of fibular centralization.

Options to reconstruct intercalary tibial defects include allografts, vascularized bone transfers, autogenous cortical grafts, endoprostheses, and Ilizarov bone transport. Five patients underwent intercalary bulk allograft reconstruction following en bloc resection of tibial sarcomas. Two patients underwent immediate fibular centralization and iliac crest bone grafting in addition to the allograft. Two patients who underwent fibular centralization during primary reconstruction united uneventfully. The remaining three patients developed nonunion, of which one was successfully salvaged by fibular centralization. A combined allograft transplant and fibular centralization with iliac crest bone grafting is an effective procedure to reconstruct the tibial diaphysis, as well as a salvage procedure for allograft nonunion.

Failure of medullary tubes. A materials analysis.

The objective of this study is to determine the effects of autoclaving on the stress, strain, ultimate tensile strength (UTS), fracture strain, modulus, and yield stress of nylon medullary tubes. There are three reports describing nylon medullary tube failure in the literature. All cases involved the use of nylon medullary tubes during open reduction internal fixation of fractured long bones. We demonstrated increased brittleness and decreased strength with increased exposure of medullary tubes to autoclaving, most dramatically after 100 autoclave cycles. Visual inspection of tubes is a clear indication of material degradation after repeated autoclaving. Furthermore, there is a significant difference in ultimate tensile strength (P < 0.0001) between tubes exposed to less than 100 sterilization cycles compared to tubes exposed to greater than 100 cycles. Likewise, there is a significant decrease in yield stress (P < 0.0004) between the same groups. We recommend disposal and replacement of nylon medullary tubes before they are exposed to 100 autoclaving cycles in order to avoid failure of the device.