Incidence and management of secondary deformities after megaendoprosthetic proximal femur replacement in skeletally immature bone sarcoma patients.

INTRODUCTION: Megaendoprosthetic reconstruction of bone defects in skeletally immature patients has led to the development of unique complications and secondary deformities not observed in adult patient cohorts. With an increasing number of megaendoprosthetic replacements performed, orthopedic oncologists still gain experience in the incidence and type of secondary deformities caused. In this study, we report the incidence, probable cause and management outcome of two secondary deformities after megaendoprosthetic reconstruction of the proximal femur: hip dysplasia and genu valgum. MATERIALS AND METHODS: Retrospective analysis of 14 patients who underwent primary and/or repeat reconstruction/surgery with a megaendoprosthetic proximal femur replacement between 2018 and 2022. RESULTS: Mean patient age was 9.1 years (range 4-17 years). Stress shielding was observed in 71.4%. Hip dislocation was the most frequent complication (50%). While four dislocations occurred without an underlying deformity, secondary hip dysplasia was identified in 58.3% (n = 7/12) of intraarticular resections and reconstructions, leading to dislocation in 71.4% (n = 5/7). A genu valgum deformity was observed in 41.6% (n = 5/12). The incidence of secondary hip dysplasia and concomitant genu valgum was 42.9% (n = 3/7). Triple pelvic osteotomy led to rebound hip dysplasia in two cases (patients aged < 10 years), whereas acetabular socket replacement led to stable hip joints over the course of follow-up. Temporary hemiepiphyseodesis was applied to address secondary genu valgum. CONCLUSIONS: Patients aged < 10 years were prone to develop secondary hip dysplasia and genu valgum following proximal femur replacement in this study. Management of secondary deformities should depend on remaining skeletal growth. Stress shielding was observed in almost all skeletally immature patients.

Slipped capital femoral epiphysis after tumor prosthesis implantation in a patient receiving chemotherapy.

While the usual etiology of slipped capital femoral epiphysis (SCFE) is idiopathic, there are many other factors that increase the predisposition to slippage. Chemotherapy can be one of them. In this article, we report a rare case of acute SCFE after tumor prosthesis implantation in a patient who received chemotherapy. A 10-year-old girl with osteosarcoma of the right distal femur underwent (neo-) adjuvant chemotherapy, wide tumor resection, and reconstruction using a growing tumor prosthesis and a short non-cemented femoral stem. Half a year after implantation, she developed aseptic loosening. Revision surgery was performed using a hydroxyapatite (HA)-coated cementless femoral stem. Postoperative plain radiographs revealed SCFE that was treated by closed reduction and screw fixation. The patient recovered without complications, and unaffected hip showed no radiographic signs of slippage on follow-up. The forces of implanting a tumor prosthesis, particularly with a non-cemented stem, can increase the risk of an acute SCFE. The controversy over prophylactic pinning of the uninvolved hip in chemotherapy-associated SCFE is unresolved. Pinning can be considered only in the presence of abnormal prodromal radiological findings.

Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum.

Background: Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods: We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan-Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results: The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P=0.02; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P=0.04; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P=0.02; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P=0.01; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion: Young age seems to positively influence patients` survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636.

The Megaendoprosthesis in Revision Arthroplasty - a Cost-revenue Analysis in the aG-DRG System. / Die Megaendoprothese im Revisionsfall ­ eine Kosten-Erlös-Analyse im aG-DRG-System.

Megaendoprosthesis offer a viable treatment in complex revision arthroplasty cases with good functional outcome. In the context of a neoplastic indication, the diagnosis-related group (DRG) I95A is usually assigned with a relative weight of 4.906 (2021). In contrast, in revision arthroplasty, the appropriate DRG is assigned, depending on the joint replacement. The additional costs compared to the invoiced DRG are to be compensated by agreeing on hospital-specific individual fees. These complex revision arthroplasties set high technical and operative demands and are mainly performed in specialised departments. We conducted a cost-benefit analysis of the use of the megaendoprosthesis in revision cases in a specialised orthopaedic clinic, as a single centre study. The question we sought to answer was: Is cost recovery possible in the modified German DRG system (aG-DRG)?A retrospective single centre analysis of treatment costs was performed. From 2018 to 2020, 113 patients treated with a megaendoprosthesis reconstruction in a referral centre due to extensive bone loss after aseptic or septic revision of a hip or knee prosthesis were included in the study. Relevant case-related cost drivers of the aG-DRG matrix (including staff and material costs of the operating theatre area and the ward) were taken into account. The actual costs were determined according to the specifications of the calculation manual published by the German institute for the remuneration system in hospitals (InEK). For each case, the contribution margin was calculated by relating the hospital's internal costs to the corresponding cost pool of the aG-DRG matrix.According to the DRG system 2021, 17 different DRGs were used for billing - in 70% based on a patient clinical complexity level (PCCL) ≥ 4. Compared with the InEK calculation, there is a deficit of -2,901 € per case in the examined parameters. The costs of physicians show a shortfall in both the operating theatre and on the ward. Implant costs, which were supposed to be compensated by hospital-specific additional charges, show a hospital-specific shortage of -2,181 €. When analysing the risk factors for cost recovery, only these showed a significant difference.Implantation of the megaendoprosthesis in revision arthroplasty is often the last option to preserve limb function. At present, despite a high degree of specialisation and process optimisation, this treatment cannot be provided cost-effectively even in tertiary care. The politically desired specialised department structure requires sufficient reimbursement for complex cases. The economic outcome of each treatment case is often unpredictable, however the surgeon is confronted with these cases and is expected to treat them. The high standard deviation indicates large differences in the cost/revenue situation of each individual case. Our results show for the first time a realistic cost analysis for megaprosthesis in revision arthroplasty and underline the importance of an adequate hospital-specific charge, individually agreed by the funding units. The calculation should include not only the implant costs, but also the increased staff costs (increased, complex planning effort, quality management, surgery time, etc.).

Association between local treatment modalities and event-free survival, overall survival, and local recurrence in patients with localised Ewing Sarcoma. Report from the Ewing 2008 trial.

BACKGROUND: Local treatment is a crucial element in the standard of care for Ewing sarcoma (EWS). While systemic treatment is improved in randomised clinical trials, local treatment modalities are discussed controversially. We analysed the association between local therapy and event-free survival (EFS), overall survival (OS), and local recurrence (LR) in prospectively collected data of patients with localised EWS. PATIENTS AND METHODS: We analysed data from the international Ewing 2008 study registered between 2009 and 2019 in 117 centres. After induction chemotherapy, patients received surgery, radiotherapy, or a combination thereof. We performed Cox regression, conducted propensity score-weighted sensitivity analysis, and performed subgroup analyses. Hazard ratios (HRs) and 95% confidence intervals are reported. RESULTS: We included 863 patients with localised EWS (surgery alone: 331, combination therapy: 358, definitive radiotherapy: 174). In patients treated with combination therapy compared to surgery alone, EFS HR was 0.84 (0.57-1.24; p = 0.38), OS HR was 0.84 (0.57-1.23; p = 0.41), and LR HR was 0.58 (0.26-1.31; p = 0.19). Hazards of any event were increased in patients treated with definitive radiotherapy compared to surgery only, HR 1.53 (1.02-2.31; p = 0.04). Patients with poor responses to chemotherapy benefitted from combination therapy over definitive surgery with an EFS HR 0.49 (0.27-0.89; p = 0.02). Patients with pelvic tumours benefitted from combination therapy over surgery only regarding LR, HR 0.12 (0.02-0.72; p = 0.02). CONCLUSION: Patients with poor responses to chemotherapy benefitted from radiotherapy added to surgery. In the whole group, radiotherapy alone as opposed to surgery alone increased the hazards of any event.

Custom-Made Metaphyseal Sleeves in "Beyond" AORI III Defects for Revision Knee Arthroplasty-Proof of Concept and Short-Term Results of a New Technique.

BACKGROUND: While off-the-shelf cones and sleeves yield good results in AORI type 2 and 3 defects in revision knee surgery, massive longitudinal defects may require a proximal tibia replacement. To achieve the best anatomical as well as biomechanical reconstruction and preserve the tibial tuberosity, we developed custom-made metaphyseal sleeves (CMSs) to reconstruct massive defects with a hinge knee replacement. METHODS: Between 2019 and 2022, 10 patients were treated in a single-center study. The indication for revision was aseptic loosening in five cases and periprosthetic joint infection in five cases. The mean number of previous revisions after the index operations was 7 (SD: 2; 4-12). A postoperative analysis was conducted to evaluate the functional outcome as well as the osteointegrative potential. RESULTS: Implantation of the CMS in rTKA was carried out in all cases, with a mean operation time of 155 ± 48 (108-256) min. During the follow-up of 23 ± 7 (7-31) months, no CMS was revised and revisions due to other causes were conducted in five cases. Early radiographic evidence of osseointegration was recorded using a validated method. The postoperative OKS showed a significant increase (p < 0.001), with a mean score of 24 (SD: 4; range: 14-31). CONCLUSION: Custom-made metaphyseal sleeves show acceptable results in extreme cases. As custom-made components become more and more common, this treatment algorithm presents a viable alternative in complex rTKA.

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma.

Purpose: Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS. Methods and Materials: The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S&RT group) and/or RT (RT group). EFS and OS were analyzed with uni- and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response. Results: S&RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose ≤ 53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose ≥ 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S&RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 (P = .42) and in the RT group 52.9%, 62.5%, and 70.3% (P = .63), respectively. Multivariable Cox regression revealed age ≥ 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S&RT group (sex, P = .96; histologic response, P = .07; tumor volume, P = .50; dose, P = .10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, P = .15; age, P = .08; sex, P = .40). Conclusions: In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.

Beyond type III Paprosky acetabular defects: are partial pelvic replacements with iliosacral fixation successful?

PURPOSE: Supra-acetabular bone loss close beyond the sciatic notch is one of the most challenging defect types for stable anatomical reconstruction in revision arthroplasty. Using reconstruction strategies from tumour orthopaedic surgery, we adapted tricortical trans-iliosacral fixation options for custom-made implants in revision arthroplasty. The aim of the present study was to present the clinical and radiological results of this extraordinary pelvic defect reconstruction. METHODS: Between 2016 and 2021, 10 patients with a custom-made pelvic construct using tricortical iliosacral fixation (see Fig. 1) were included in the study. Follow-up was 34 (SD 10; range 15-49) months. Postoperatively CT scans evaluating the implant position were performed. Functional outcome and the clinical results were recorded. RESULTS: Implantation was possible as planned in all cases in 236 (SD 64: range 170-378) min. Correct centre of rotation (COR) reconstruction was possible in nine cases. One sacrum screw crossed a neuroforamen in one case without clinical symptoms. During the follow-up period, four further operations were required in two patients. There were no individual implant revisions or aseptic loosening recorded. The Harris Hip Score increased significantly from 27 Pts. to 67 Pts. with a mean improvement of 37 (p < 0.005). EQ-5D developed from 0.562 to 0.725 (p = 0.038) as a clear improvement in quality of life. CONCLUSION: Custom-made partial pelvis replacement with iliosacral fixation offers a safe solution in "beyond Paprosky type III defects" for hip revision arthroplasty. Due to meticulous planning, precise implantation with good clinical outcome can be achieved. Furthermore, the functional outcome and patient satisfaction increased significantly showing promising early results with a relatively low complication rate.

Cortical Desmoid of the Distal Femur-Incidentaloma or Insertional Tendinopathy?

BACKGROUND: The cortical desmoid (DFCI) of the posteromedial femoral condyle is considered an asymptomatic incidental finding in adolescents without clinical relevance. The aim of this study was to evaluate the clinical relevance of DFCI from both a tumor orthopedic and sports medicine point of view. METHODS: n = 23 patients (13.74 ± 2.74 years; nineteen female, four male) with DFCI of the posteromedial femoral condyle were included. A localized posteromedial knee pain on exertion was differentiated from non-specific knee pain. Symptom duration, additional pathologies, number of MRIs, sports activity and training intensity, downtime, therapeutic modalities, and relief/remission of symptoms were documented. The Tegner activity scale (TAS) and Lysholm score (LS) were collected. The influence of specific posteromedial pain, MRI presence of paratendinous cysts, sports level as well as physiotherapy on downtime and LS/TAS was statistically analyzed. RESULTS: 100% reported knee symptoms at initial presentation. A localized posteromedial pain was documented in 52%. In 16/23 (70%) additional functional pathologies were diagnosed. Patients were physically highly active with high training intensities (6.52 ± 5.87 h/week) and performance level (65% competitive vs. 35% recreational). Patients underwent 1.91 ± 0.97 MRIs (max four). Symptom duration was 10.48 ± 11.02 weeks. A follow-up examination was performed after 12.62 ± 10.41 months (n = two lost to follow-up). 17/21 had physiotherapy, on average 17.06 ± 13.33 units. Overall downtime was 13.39 ± 12.50 weeks, the return-to-sports (RTS) rate 81%. 100%/38% reported a relief/remission of complaints. LS was 93.29 ± 7.95, median TAS before onset of knee complaints/at follow-up 7 (6-7)/7 (5-7). Specific posteromedial pain, presence of paratendinous cysts, sports level and physiotherapy had no significant influence on downtime and outcome parameters (n.s.). CONCLUSIONS: DFCI as a pathognomonic finding is recurrently encountered in the MRIs of children and adolescents. This knowledge is essential to spare patients from overtreatment. Contrary to the literature, the present results implicate a clinical relevance of DFCI particularly in those who are physically highly active with localized pain on exertion. Structured physiotherapy as basic treatment is recommended.

Evaluation of the Effect of Photodynamic Therapy on CAM-Grown Sarcomas.

Resection margin adequacy plays a critical role in the local control of sarcomas. Fluorescence-guided surgery has increased complete resection rates and local recurrence-free survival in several oncological disciplines. The purpose of this study was to determine whether sarcomas exhibit sufficient tumor fluorescence (photodynamic diagnosis (PDD)) after administration of 5-aminolevulinic acid (5-ALA) and whether photodynamic therapy (PDT) has an impact on tumor vitality in vivo. Sixteen primary cell cultures were derived from patient samples of 12 different sarcoma subtypes and transplanted onto the chorio-allantoic membrane (CAM) of chick embryos to generate 3-dimensional cell-derived xenografts (CDXs). After treatment with 5-ALA, the CDXs were incubated for another 4 h. Subsequently accumulated protoporphyrin IX (PPIX) was excited by blue light and the intensity of tumor fluorescence was analyzed. A subset of CDXs was exposed to red light and morphological changes of both CAMs and tumors were documented. Twenty-four hours after PDT, the tumors were excised and examined histologically. High rates of cell-derived engraftments on the CAM were achieved in all sarcoma subtypes and an intense PPIX fluorescence was observed. PDT of CDXs resulted in a disruption of tumor-feeding vessels and 52.4% of CDXs presented as regressive after PDT treatment, whereas control CDXs remained vital in all cases. Therefore, 5-ALA mediated PDD and PDT appear to be promising tools in defining sarcoma resection margins (PDD) and adjuvant treatment of the tumor bed (PDT).

Return to Sports and Activity in Tumor Orthopaedics. / Wiederkehr zu körperlicher Aktivität und Sport in der Tumororthopädie.

As survival rates associated with the multimodal treatment of malignant bone cancer (osteosarcoma and Ewing's sarcoma) are satisfactory, health-related quality of life and the return to activity and sports by the affected patients have attracted increasing attention in recent years. Nowadays, limbs can be salvaged for most patients using modular endoprostheses. Such patients are typically adolescents and young adults who have high activity levels and thereby high demands for multimodal cancer treatment. This study aimed to evaluate the activity levels and sporting proficiencies that can be attained after modular endoprosthetic treatment of bone sarcomas as well as the extent to which physiotherapeutic and sports interventions influence functional outcome and activity levels.This non-systematic review of the literature focused on the return to activity and sports after modular endoprosthetic treatment of lower extremities bone sarcomas in adolescents and young adults. The electronic database PubMed was screened for relevant publications on this issue. A treatment algorithm for return to activity and sports in tumor orthopaedics is proposed.The objective activity level (gait cycles per day and gait intensities) in patients treated for bone sarcomas is reduced in short- and long-term follow-ups compared with healthy controls and patients with other cancers (leukaemia). Although a negative impact is observed in terms of motor performance, it shows improvement over time. Functional assessment at 12 postoperative months is sensible as neoadjuvant chemotherapy is completed by then. In long-term follow-up, patients with bone sarcomas can achieve high sports activity levels, i.e., type of sport, frequency/week and UCLA score, after modular endoprosthetic reconstruction. The maximum level is attained at 5 years postoperatively. Nevertheless, there is a shift from high- and intermediate- to low-impact sports. Only 20% of the patients participate in school sports regularly without limitations. The localisation of bone sarcoma, but not the rate of postoperative complications, influences the postoperative activity level. Individualised sports-related interventions during and after multimodal treatment can improve the short-term activity levels; moreover, "serious games" can improve motor performance and postural control. There is no evidence that intense activity levels leads to early loosening of the endoprosthesis. There is insufficient valid data on activity and sports after modular endoprosthetic treatment of bone sarcomas of the upper extremities.High preoperative activity levels of young patients with bone sarcomas must be considered in tumour orthopaedics. Limitations on sports activities have a significant negative impact on the quality of life and mental health of such patients. Therefore, tumour orthopaedic treatment has to focus on preserving an improvement in these factors. The overall existing evidence concerning this issue is weak. Additional studies to evaluate the ability to return to specific sports activities are desirable, as well as prospective interventional studies.

Classic Type of Epithelioid Sarcoma of the Distal Upper Extremity: Clinical and Oncological Characteristics.

BACKGROUND: The classic type of epithelioid sarcoma (ES) is a rare, aggressive soft tissue neoplasm that most commonly affects the distal upper extremities of young patients. This study aimed to assess clinical features and provide a long-term report of the oncological outcome. METHODS: We retrospectively analyzed our clinical database for patients with ES of the distal upper extremities. RESULTS: Twenty-three patients with ES of the distal upper extremity were treated surgically between January 1990 and August 2018. ES affected most commonly the palmar side of young patients. The most common site affected by a sarcoma was the wrist in 47.8% of cases, followed by metacarpals and fingers with 34.8% and 17.4%, respectively. Most of the patients were treated according to the protocols of interdisciplinary tumor boards with multimodal therapy. A local recurrence was observed in 7 patients (30.4%). The 5 - and 10-year recurrence-free survival was 80.4% (95% confidence interval [CI]: 68.6-76.8) and 60.9% (95% CI: 53.5-68.3), respectively. The 5- and 10-years disease-specific survival was 89.9% (95% CI: 87-92.8) and 61.9% (95% CI: 56.5-67.3), respectively. Five patients (21.7%) had metastasis in regional lymph nodes. CONCLUSION: The classic type of ES represents a group of high-grade sarcomas, which affect the dominantly distal upper extremity. Specific clinical, diagnostic, and oncological characteristics make it difficult to diagnose and therapy. Wide tumor resection as a part of multimodal therapy remains a more viable and common treatment option for patients with ES on distal extremities. High rates of lymph node metastasis are typical for ES.

Interdisciplinarity in Diagnostics of Bone Lesions. / Interdisziplinarität in der Diagnosefindung häufiger Knochenläsionen im klinischen Alltag.

INTRODUCTION: Due to substantial advances in all medical disciplines, interdisciplinary cooperation is of major relevance in modern medicine. Given the rarity of benign and malignant bone tumours, diagnosis and therapy of these lesions is especially challenging. Focusing on typical cases, it is the aim of this article to illustrate the necessity of interdisciplinary cooperation. METHODS: The scope of this article is to highlight the particular significance of interdisciplinarity in the diagnosis of bone tumours. To this end, we illustrate the interdisciplinary approach in typical clinical cases. RESULTS AND DISCUSSION: The article demonstrates that a combined clinico-radiological approach is essential in the diagnosis of leave-me-alone lesions, and it underlines the essential role of an interdisciplinary correlation of clinical context, radiology and pathology in the interpretation of bone tumour biopsies. It documents the experience that all clinical aspects and diagnostic findings need to be synoptically integrated in a joint interdisciplinary tumour board to eventually find the correct diagnosis. CONCLUSION: It is generally accepted that the diagnosis of a bone tumour can often not be made by the pathologist alone but essentially requires interdisciplinary cooperation.

Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts.

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.

Transcriptome-Wide Gene Expression Profiles from FFPE Materials Based on a Nuclease Protection Assay Reveals Significantly Different Patterns between Synovial Sarcomas and Morphologic Mimickers.

BACKGROUND: Transcriptome profiling provides large data on tumor biology, which is particularly valuable in translational research and is becoming more and more important for clinical decision-making as well. RNA sequencing is considered to be the gold standard for this. However, FFPE material, as the most available material in routine pathology, has been an undefeatable obstacle for RNAseq. Extraction-free nuclease protection assays have the potential to be a reliable alternative method for large-scale expression profiling. The aim of this study was to validate and test the basic feasibility, technical applicability robustness, and reliability of the HTG transcriptome profiling (HTP) assay on clinical tumor samples. METHODS: FFPE samples from 44 synovial sarcomas (SyS) and 20 spindle cell sarcomas (SpcS) were used. The HTP assay was performed on 10 µm thin FFPE slides. After nuclease protection in the HTG Edge Seq System, libraries were generated for sequencing on an Illumina NextSeq 500 platform. Fastq data were parsed and then analyzed by using the HTG analysis platform EdgeSeq REVEAL. Immunohistochemistry was performed to validate the expression of TLE1. RESULTS: The technical application of the HTP Panel revealed robust and reliable results with 62 samples, and only 2 samples failed due to an incomplete digestion of gDNA. The analysis, performed at the analysis platform REVEAL, showed 5964 genes being significantly differentially expressed between SpcS and SyS. In particular, overexpression of the known marker TLE1 in synovial sarcoma could be recovered, which underlines the reliability of this system. DISCUSSION: Transcriptome profiling gets more and more important for tumor research and diagnostics. Among other established technologies, the HTP Panel has shown to be a feasible method to get robust and reliable results. Thereby, this method needs very few sample-input by getting a success-rate of 96.88%, which indicates the upper average range, compared to other technologies working with FFPE tissue. CONCLUSION: The nuclease protection assay-based HTP Panel is a feasible method for adequate transcriptome profiling with low sample input and therefore is suitable for further research of biomarkers.

Reconstruction of Paprosky III defects with custom-made implants: do we get them in the correct position? : short-term radiological results.

AIMS: The aim of this study was to examine the implant accuracy of custom-made partial pelvis replacements (PPRs) in revision total hip arthroplasty (rTHA). Custom-made implants offer an option to achieve a reconstruction in cases with severe acetabular bone loss. By analyzing implant deviation in CT and radiograph imaging and correlating early clinical complications, we aimed to optimize the usage of custom-made implants. METHODS: A consecutive series of 45 (2014 to 2019) PPRs for Paprosky III defects at rTHA were analyzed comparing the preoperative planning CT scans used to manufacture the implants with postoperative CT scans and radiographs. The anteversion (AV), inclination (IC), deviation from the preoperatively planned implant position, and deviation of the centre of rotation (COR) were explored. Early postoperative complications were recorded, and factors for malpositioning were sought. The mean follow-up was 30 months (SD 19; 6 to 74), with four patients lost to follow-up. RESULTS: Mean CT defined discrepancy (Δ) between planned and achieved AV and IC was 4.5° (SD 3°; 0° to 12°) and 4° (SD 3.5°; 1° to 12°), respectively. Malpositioning (Δ > 10°) occurred in five hips (10.6%). Native COR reconstruction was planned in 42 cases (93%), and the mean 3D deviation vector was 15.5 mm (SD 8.5; 4 to 35). There was no significant influence in malpositioning found for femoral stem retention, surgical approach, or fixation method. CONCLUSION: At short-term follow-up, we found that PPR offers a viable solution for rTHA in cases with massive acetabular bone loss, as highly accurate positioning can be accomplished with meticulous planning, achieving anatomical reconstruction. Accuracy of achieved placement contributed to reduced complications with no injury to vital structures by screw fixation.Cite this article: Bone Joint J 2022;104-B(10):1110-1117.

[Bone tumours-What's new in the 2020 WHO classification and beyond]. / Knochentumoren ­ Neues in und jenseits der WHO-Klassifikation 2020.

The recent WHO classification of Bone Tumours (2020) has introduced several changes. Conceptionally, small round cell sarcomas are now summarized in a distinct chapter, acknowledging their occurrence in both, bone and soft tissue. In the light of new molecular findings some diagnostic categories, such as fibrohistiocytic tumors, have been abandoned, and a few new entities have been added to the classification. Finally, systematic changes were made with regard to the terminology employed in the classification of chondrogenic tumours, and modifications have been made with respect to the biological potential of some lesions. This article summarizes the major changes made, underscoring the elementary role of an interdisciplinary approach in the diagnosis and management of bone lesions.

Pathological Fractures in Benign Bone Lesions - Diagnosis and Therapy. / Die pathologische Fraktur bei benignen Knochenläsionen - Diagnostik und Therapie.

INTRODUCTION: Most tumour-related pathological fractures occur in patients with bone metastases. However, in mostly younger patients, a pathological fracture can be due to both a benign or a malignant bone tumour. Making the correct diagnosis from among these two differential diagnoses is enormously important. If the tumour is malignant, treating the fracture inevitably leads to tumour cell contamination and can significantly worsen the oncological situation. The aim of this review article is firstly to provide the reader with diagnostic assistance in the case of suspected pathological fractures, and secondly to focus on the treatment of pathological fractures occurring with benign bone tumours. METHODS: This is a non-systematic review of the diagnosis and treatment of pathological fractures in benign bone tumours or tumour-like lesions, based on an electronic PubMed database search. We also present our own procedures, in particular for ruling out a malignant bone tumour. RESULTS AND DISCUSSION: Whenever a fracture occurs in the absence of sufficient traumatic force, the possibility of a pathological fracture should always be considered. As well as taking a general history for a possible primary tumour, it is particularly important to ask the patient whether they had any pain before the fracture occurred. If the findings from clinical examination or conventional radiological imaging give rise to suspicion of a pathological fracture, an MRI of the affected skeletal section with contrast medium should be carried out before commencing any fracture treatment. A CT scan is also helpful for accurately assessing bone destruction. If a malignant or locally aggressive benign bone tumour such as giant cell tumour (GCT) or aneurysmal bone cyst (ABC) cannot be definitively ruled out through imaging, a biopsy is essential. The bone biopsy must always be carried out on the assumption that the histological work-up will reveal a malignant bone tumour; it must therefore be performed according to strict oncological criteria. If the radiological diagnosis is unambiguous, e. g., a juvenile bone cyst (JBC) or a non-ossifying fibroma (NOF), conservative treatment of the fracture can be considered, depending on the location. In the presence of a locally aggressive benign bone tumour such as a GCT or ABC, curettage of the tumour must be carried out as well as treating the fracture. With GCT in particular, neoadjuvant therapy with denosumab prior to curettage and osteosynthesis or en bloc resection of the tumour should be considered, depending on the extent of the tumour. CONCLUSION: Pathological fractures, especially in younger patients, should not be overlooked. Only after a malignant or benign locally aggressive bone tumour has been definitively ruled out should fracture treatment be performed. In the presence of a locally aggressive bone tumour, as well as treating the fracture, it is usually necessary to perform curettage of the tumour - also en bloc resection, where applicable, in the case of a GCT. Depending on the location, benign, non-aggressive tumours can be treated conservatively if necessary.

Are Postoperative Infections in the First 12 Months after Wide Resection and Megaprosthetic Replacement Associated with the Survival of Osteosarcoma Patients? Results of a Multicenter Study.

Recent retrospective studies suggested that early postoperative infections might be associated with a survival benefit for extremity osteosarcoma patients, but the reported results have been conflicting. The files of 437 patients with a newly diagnosed, high-grade osteosarcoma of the extremities treated at 5 referral centers in Germany and Austria between 1989 and 2016 were retrospectively evaluated. All patients underwent multi-agent chemotherapy and limb-sparing tumor excision, followed by endoprothetic replacement. We used the Kaplan-Meier method to calculate survival curves, which we compared with the log-rank test. With a median follow-up of 100 months (interquartile range, 49-155 months), local recurrence (LR) probability, event-free survival (EFS), and disease-specific survival (DSS) after 5 years in this selected patient cohort amounted to 5%, 67%, and 79%, respectively, and 46 patients (10.5%) developed an early postoperative infection. We found no significant differences in LR, EFS, or DSS between patients with and without early infections, and there were no differences in known prognostic factors between the two groups. However, in subgroup analyses patients with a poor response to neoadjuvant chemotherapy and an early infection had a better DSS compared to patients without early infections (93% vs. 62% after 5 years, p = 0.044). Provided that our findings can be validated in separate patient cohorts, we believe that patient outcome after adjuvant immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for good and poor responders to neoadjuvant chemotherapy in future studies.

Prognostic Factors for Leiomyosarcoma with Isolated Metastases to the Lungs: Impact of Metastasectomy.

BACKGROUND: Leiomyosarcoma (LMS) most frequently metastasizes to the lung. Metastatic LMS is considered incurable. Selected patients may benefit from pulmonary metastasectomy (PM) within multimodal therapy. This study analyzed the prognostic relevance of clinicopathologic factors in these patients. METHODS: Patients with metastatic LMS to the lung treated in our center from 2004 to 2020 were included in this single-center retrospective study. Overall survival (OS), progression-free survival (PFS), and prognostic factors were analyzed. RESULTS: The study had 64 patients (33 males, 52%) with metastatic LMS to the lung. The 5-year OS was 55% after the diagnosis of pulmonary metastases. Age older than 60 years at the primary tumor diagnosis, primary tumor larger than 70 mm, and five or more lung metastases were associated with poorer OS. Of the 64 patients, 44 underwent PM. The postoperative mortality rate was 0%. The patients selected for PM were younger and had smaller primary tumors, fewer metastases, and metastases that more often were metachronous. Metastasis grade (G1 vs. G2/3) and size (20-mm cutoff) were significant prognostic factors for OS (p = 0.05) and PFS (p = 0.028) after PM, respectively. The 44 patients who underwent PM had a survival benefit compared with the patients who were selected but did not undergo PM (n = 6) and the patients who were not selected for PM (n = 14). Three patients (7%) were alive and free of disease at the last follow-up visit respectively 5.5, 9, and 12 years after PM. CONCLUSIONS: For patients with leiomyosarcoma, PM is safe. Despite aggressive multimodal treatment, most patients will experience recurrence and eventually die of their disease. However, a small subgroup of patients could potentially be cured after PM.