Clinical and functional outcome after partial or total claviculectomy without reconstruction for oncologic causes.

BACKGROUND: To achieve clear margins in rare malignant clavicular neoplasms, claviculectomy may become necessary. This study aimed to review clinical, functional, and oncologic outcomes following partial or total claviculectomy without reconstruction. METHODS: This study retrospectively included 15 patients from 2 tertiary sarcoma centers (mean age, 42.6 ± 20.3 years; 66.7% male patients). The median length of clinical and oncologic follow-up was 48.0 months (interquartile range [IQR], 24.0-83.5 months). Functional follow-up (Musculoskeletal Tumor Society score and QuickDASH score [short version of the Disabilities of the Arm, Shoulder and Hand questionnaire]) was available in 9 patients at a median of 36.0 months (IQR, 20.0-100.0 months). RESULTS: Of the 15 patients, 7 underwent total claviculectomy; 5, partial lateral claviculectomy; and 3, partial medial claviculectomy. No postoperative complications emerged. The median Musculoskeletal Tumor Society and QuickDASH scores at latest follow-up amounted to 26.0 points (IQR, 24.0-29.0 points) and 18.0 points (IQR, 11.0-22.0 points), respectively. Notably, scores tended to be lower in patients who underwent total claviculectomy (n = 2) in comparison to partial claviculectomy (n = 7). CONCLUSION: Satisfactory clinical and functional results can be achieved following partial or total claviculectomy without reconstruction, with a low complication rate and acceptable mid- to long-term function.

Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue.

In the last decade, new tumor entities have been described, including EWSR1/FUS::NFATC2-rearranged neoplasms of different biologic behavior. To gain further insights into the behavior of these tumors, we analyzed a spectrum of EWSR1/FUS::NFATC2-rearranged neoplasms and discuss their key diagnostic and molecular features in relation to their prognosis. We report five patients with EWSR1/FUS::NFATC2-rearranged neoplasms, including one simple bone cyst (SBC), two complex cystic bone lesions lacking morphological characteristics of SBC, and two sarcomas. In three cases, fluorescence in situ hybridization (FISH) and in all cases copy number variation (CNV) profiling and fusion analyses were performed. All patients were male, three cystic lesions occurred in children (aged 10, 14, and 17 years), and two sarcomas in adults (69 and 39 years). Fusion analysis revealed two FUS::NFATC2 rearrangements in two cystic lesions and three EWSR1::NFATC2 rearrangements in one complex cystic lesion and two sarcomas. EWSR1 FISH revealed tumor cells with break-apart signal without amplification in one complex cystic lesion and EWSR1 amplification in both sarcomas was documented. CNV analysis showed simple karyotypes in all cystic lesions, while more complex karyotypes were found in NFATC2-rearranged sarcomas. Our study supports and expands previously reported molecular findings of EWSR1/FUS::NFATC2-rearranged neoplasms. The study highlights the importance of combining radiology and morphologic features with molecular aberrations. The use of additional molecular methods, such as CNV and FISH in the routine diagnostic workup, can be crucial in providing a correct diagnosis and avoiding overtreatment.

T-regulatory cells predict clinical outcome in soft tissue sarcoma patients: a clinico-pathological study.

BACKGROUND: Soft tissue sarcomas (STS) are generally considered non-immunogenic, although specific subtypes respond to immunotherapy. Antitumour response within the tumour microenvironment relies on a balance between inhibitory and activating signals for tumour-infiltrating lymphocytes (TILs). This study analysed TILs and immune checkpoint molecules in STS, and assessed their prognostic impact regarding local recurrence (LR), distant metastasis (DM), and overall survival (OS). METHODS: One-hundred and ninety-two surgically treated STS patients (median age: 63.5 years; 103 males [53.6%]) were retrospectively included. Tissue microarrays were constructed, immunohistochemistry for PD-1, PD-L1, FOXP3, CD3, CD4, and CD8 performed, and staining assessed with multispectral imaging. TIL phenotype abundance and immune checkpoint markers were correlated with clinical and outcome parameters (LR, DM, and OS). RESULTS: Significant differences between histology and all immune checkpoint markers except for FOXP3+ and CD3-PD-L1+ cell subpopulations were found. Higher levels of PD-L1, PD-1, and any TIL phenotype were found in myxofibrosarcoma as compared to leiomyosarcoma (all p < 0.05). The presence of regulatory T cells (Tregs) was associated with increased LR risk (p = 0.006), irrespective of margins. Other TILs or immune checkpoint markers had no significant impact on outcome parameters. CONCLUSIONS: TIL and immune checkpoint marker levels are most abundant in myxofibrosarcoma. High Treg levels are independently associated with increased LR risk, irrespective of margins.

Broadening the spectrum of NTRK rearranged mesenchymal tumors and usefulness of pan-TRK immunohistochemistry for identification of NTRK fusions.

Fusions involving NTRK1, NTRK2, and NTRK3 are oncogenic drivers occurring in a spectrum of mesenchymal neoplasms ranging from benign to highly malignant tumors. To gain further insights into the staining profile with the pan-TRK assay, we analyzed a large number of soft tissue sarcomas and correlated our findings with molecular testing. Additionally, we expand the spectrum of NTRK-fusion tumors by reporting a mesenchymal lesion in the lung as well as a mesenchymal skin lesion in the spectrum of benign fibrous histiocytoma with NTRK-fusion. We retrospectively reviewed soft tissue sarcomas diagnosed at the Diagnostic and Research Institute of Pathology, Medical University of Graz, between 1999 and 2019, and cases from the consultation files of one of the authors (BLA). In total, 494 cases were analyzed immunohistochemically with pan-TRK antibody (clone EPR17341, RTU, Roche/Ventana) and positive cases (defined as any cytoplasmic/nuclear staining in more than 1% of tumor cells) underwent next-generation sequencing (NGS). Immunohistochemical staining was observed in 16 (3.2%) cases. Eleven cases with focal weak and moderate cytoplasmic/membranous or focal moderate to strong nuclear staining did not harbor an NTRK-fusion (three synovial sarcomas, three leiomyosarcomas, two extraskeletal myxoid chondrosarcomas, and one each: dedifferentiated liposarcoma, pleomorphic liposarcoma, and myxofibrosarcoma). Four cases showed strong diffuse nuclear and/or cytoplasmatic staining, and one case showed diffuse, but weak cytoplasmic staining. All these cases demonstrated an NTRK-fusion (LMNA-NTRK1, IRF2BP2-NTRK1, TMB3-NTRK1, ETV6-NTRK3, RBPMS-NTRK3). Pan-TRK assay (clone EPR17341, RTU, Roche, Ventana) immunohistochemistry serves as a reliable diagnostic marker that can also be expressed in non-NTRK-rearranged mesenchymal neoplasms. It can be used as a surrogate marker for identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement, if patients are undergoing targeted therapy. Additionally, we identified NTRK-fusion-positive, primary mesenchymal tumors of the lung and the skin.

Cat at home? Cat scratch disease with atypical presentations and aggressive radiological findings mimicking sarcoma, a potential diagnostic pitfall.

Background and purpose - Cat scratch disease (CSD) is a self-limiting disease caused by Bartonella (B.) henselae. It is characterized by granulomatous infection, most frequently involving lymph nodes. However, it can present with atypical symptoms including musculoskeletal manifestations, posing a diagnostic challenge. We describe the prevalence and demographics of CSD cases referred to a sarcoma center, and describe the radiological, histological, and molecular findings.Patients and methods - Our cohort comprised 10 patients, median age 27 years (12-74) with clinical and radiological findings suspicious of sarcoma.Results - 7 cases involved the upper extremities, and 1 case each involved the axilla, groin, and knee. B. henselae was found in 6 cases tested using polymerase chain reaction and serology in 5 cases. 9 cases were soft tissue lesions and 1 lesion involved the bone. 1 patient had concomitant CSD with melanoma metastasis in enlarged axillary lymph nodes. On MRI, 5 soft tissue lesions were categorized as probably inflammatory. In 3 cases, with still detectable lymph node structure and absent or initial liquefaction, the differential diagnosis included lymph node metastasis. A sarcoma diagnosis was suggested in 4 cases. The MRI imaging features of the bone lesion were suspicious of a bone tumor or osteomyelitis.Interpretation - Atypical imaging findings cause a diagnostic challenge and the differential diagnosis includes malignant neoplasms (such as sarcoma or carcinoma metastasis) and other infections. The distinction between these possibilities is crucial for treatment and prognosis.

Incidence, treatment and outcome of abdominal metastases in extremity soft tissue sarcoma: Results from a multi-centre study.

BACKGROUND AND OBJECTIVES: Abdominal metastases (AM) from soft tissue sarcoma (STS) are rare and prognosis is poor. The aims of the study were to (a) identify risk factors for the development of AM and to (b) investigate the outcome of AM-patients. METHODS: Seven-hundred-sixty-nine STS-patients with localised disease at diagnosis treated at three tumour centres (2000-2016) were retrospectively included (409 males; mean age, 55.6 years [range, 8-96 years]; median follow-up, 4.1 years [interquartile-range, 2.5-6.6 years]). RESULTS: Two-hundred-two patients (26.3%) developed secondary metastases, and 24 of them AM (3.1%). Ten patients developed first AM (FAM) after a mean of 2.4 years and 14 patients late AM (LAM, after being diagnosed with metastases to other sites) after a mean of 2.0 years. Patients with liposarcoma had a significantly higher risk of developing AM (P = .007), irrespective of grading. There was no difference in post-metastasis-survival (PMS) between patients with AM at any time point and those with metastases to other sites (P = .585). Patients with LAM or FAM showed no difference in post-abdominal-metastasis-survival (P = .884). CONCLUSIONS: Survival in patients with AM is poor, irrespective of whether they develop secondarily to other metastases or not. Patients at high-risk of AM (ie, liposarcoma) may be followed-up regularly by abdominal-ultrasound/CT.

Benefit of Adjuvant Radiotherapy for Local Control, Distant Metastasis, and Survival Outcomes in Patients with Localized Soft Tissue Sarcoma: Comparative Effectiveness Analysis of an Observational Cohort Study.

BACKGROUND: This study aimed to quantify the benefit of adjuvant radiotherapy (AXRT) for local control, distant metastasis, and long-term survival outcomes in patients with localized soft tissue sarcoma (STS). METHODS: This single-center retrospective observational study enrolled 433 STS patients who underwent surgery with curative intent. An inverse probability of treatment-weighted (IPTW) analysis was implemented to account rigorously for imbalances in prognostic variables between the adjuvant treatment groups. RESULTS: During a median follow-up period of 5.5 years, the study observed 38 local recurrences (9%), 73 occurrences of distant metastasis (17%), 63 STS-related deaths (15%), and 57 deaths from other causes (13%). As expected, patients receiving AXRT (n = 258, 60%) were more likely to have high-grade G3 tumors (p < 0.0001) than patients not receiving AXRT. A crude analysis showed that AXRT was not associated with improved recurrence-free survival [hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.72-1.38; p = 0.98]. However, after IPTW, AXRT was associated with a 38% relative reduction in the risk of recurrence or death (HR 0.62; 95% CI 0.39-1.00; p = 0.05). This benefit was driven by a strong reduction in the risk of local recurrence (HR 0.42; 95% CI 0.19-0.91; p = 0.03), whereas the relative risk of distant metastasis (HR 0.69; 95% CI 0.39-1.25; p = 0.22) and overall survival (HR 0.76; 95% CI 0.44-1.30; p = 0.32) were only nonsignificantly in favor of AXRT. An exploratory analysis showed an overall survival benefit of AXRT for patients with high-grade G3 tumors (HR 0.51; 95% CI 0.33-0.78; p = 0.002). However, this finding may have been attributable to residual confounding. CONCLUSION: In this observational cohort, AXRT was associated with a 58% reduction in the relative risk of local recurrence. No consistent association between AXRT and lower risks of distant metastasis or death was observed.

Epiphyseal hyperplasia caused by an ectopic ossification center of the distal tibia: presentation of a pediatric case with 13 years of radiological surveillance.

Herein, we report the case of a 4-year-old boy, who presented with a cortical lytic lesion of his distal tibia. It was located eccentrically, measured 2 cm in its craniocaudal diameter, and was associated with a lamella-like soft-tissue mineralization that resembled a periosteal reaction. Thus, the lesion's radiographic features were initially suggestive of an aggressive disease. However, further imaging revealed the lesion to be of cartilaginous origin and to extend into the metaphysis, thus creating the aspect of hyperplastic epiphyseal cartilage. This cartilaginous hyperplasia was likely caused by an ectopic ossification center, although no similar cases have yet been reported. As radiology and clinics no longer indicated the imminent threat of a high-grade malignancy, we decided against a biopsy to avoid interfering with epiphyseal growth. However, because of the unprecedented nature of the given constellation, we closely monitored the lesion radiologically to rule out an untypical manifestation of a benign but potentially expanding lesion, in addition to a growth disturbance resulting from the lesion itself. However, further imaging indicated that mineralization and ossifications, which were already present at the lesion's initial presentation, increased over time, until the lesion fully disappeared after 13 years of clinical and radiological surveillance. This case is outstanding because of its singular morphology and the long-term follow-up that illustrates its self-limiting natural course. This report provides support in differential diagnosis to help discriminate potentially self-limiting conditions from other diseases that may require invasive diagnosis and/or therapy.

Current knowledge in orthopaedic surgery on recommending sport activities after total hip and knee replacement.

The increasing number of younger patients with total hip arthroplasty and total knee arthroplasty sets higher demands on the postoperative quality of life. When it comes to athletic activity, recommendations and guidelines for sports remain unclear. We have reviewed published literature to determine the extent to which patients resume their athletic activities postoperatively, and what would be the best choice. Golf and double tennis remain the most recommended activities. No-impact, low power sports like swimming and bicycling are generally allowed. Jogging is not considered as a factor for short-term implant failure, but a long-term analysis is needed. Contact and high-impact sports like football or basketball are not recommended. There are no recommendations regarding alpinism and field hockey.

The Prognostic Impact of Unplanned Excisions in a Cohort of 728 Soft Tissue Sarcoma Patients: A Multicentre Study.

BACKGROUND: Unplanned excisions (UE) of soft tissue sarcomas (STS) carry a high risk for local recurrence (LR) due to marginal/intralesional resections. However, there are reports about improved prognosis for UE patients who have re-resection compared with patients who undergo planned surgery. The present multicentre study was designed to define characteristics of UE patients and to investigate the impact of UE on subsequent therapy and patient outcomes. METHODS: A total of 728 STS patients (376 males, 352 females; mean age: 58 years) who underwent definite surgery at one of three tumour centres were retrospectively included. Time-to-event analyses were calculated with log-rank and Gray's tests, excluding patients with primary metastasis (n = 59). A propensity-score (PS) of being in the UE group was estimated, based on differences at baseline between the UE group and non-UE group. An inverse-probability-of-UE weight (IPUEW) was generated and time-to-event analyses calculated after IPUEW weighting. RESULTS: Before referral, 38.6% of patients (n = 281) had undergone UE. Unplanned excision patients were younger (p = 0.036), rather male (p = 0.05), and had smaller (p < 0.005), superficially located tumours (p < 0.005). Plastic reconstructions (p < 0.005) and adjuvant radiotherapy (p = 0.041) more often were needed at re-resection. In univariable analysis, re-resected patients had improved overall survival (OS; p = 0.027) and lower risk of distant metastasis (DM; p = 0.002) than primarily resected patients, whereas risk of LR was similar (p = 0.359). After weighting for the IPUEW, however, differences in terms of OS (p = 0.459) and risk of DM (p = 0.405) disappeared. CONCLUSIONS: The present study does not support prior findings of improved outcome for UE patients. Unplanned excisions have a major impact on subsequent therapy, yet they do not seem to affect negatively the long-term oncology outcome.

Can Multistate Modeling of Local Recurrence, Distant Metastasis, and Death Improve the Prediction of Outcome in Patients With Soft Tissue Sarcomas?

BACKGROUND: Exploration of the complex relationship between prognostic indicators such as tumor grade and size and clinical outcomes such as local recurrence and distant metastasis in patients with cancer is crucial to guide treatment decisions. However, in patients with soft tissue sarcoma, there are many gaps in our understanding of this relationship. Multistate analysis may help us in gaining a comprehensive understanding of risk factor-outcome relationships in soft tissue sarcoma, because this methodology can integrate multiple risk factors and clinical endpoints into a single statistical model. To our knowledge, no study of this kind has been performed before in patients with soft tissue sarcoma. QUESTIONS/PURPOSES: We implemented a multistate model of localized soft tissue sarcoma to statistically evaluate the relationship among baseline risk factors, recurrence, and death in patients with localized soft tissue sarcoma undergoing curative surgery. METHODS: Between 1998 and 2015, our center treated 539 patients for localized soft tissue sarcoma with surgery as curative intent. Of those, 96 patients (18%) were not included in this single-center retrospective study owing to missing baseline histopathology data (n = 3), not yet observed followup (n = 80), or because a neoadjuvant treatment approach in the presence of synchronous distant metastasis was used (n = 13), leaving 443 patients (82%) for the current analysis, of which 40 were lost to followup during the first year after surgery. All patients had tumors of the stages I to III according to the American Joint Committee on Cancer Stages. The median age of the patients was 62 years (range, 16-96 years), and 217 patients (49%) were female. Three hundred-forty-six patients (78%) had tumors of high grade (Grades 2 and 3), and 310 (70%) tumors were greater than 5 cm in maximum diameter. Patients who had died during the first year of followup were included in this analysis. Median followup for the 443 study patients was 6 years, with 84%, 52%, and 23% of patients being followed for more than 1, 5, and 10 years, respectively. The 15-year cumulative incidences of local recurrence, distant metastasis, and death from any cause, using a competing risk analysis, were 16% (95% CI, 11%-22%), 21% (95% CI, 17%-26%), and 55% (95% CI, 44%-67%), respectively. Wide resection with a margin of 1 mm was the preferred treatment for all patients, except for those with Grade 1 liposarcoma where a marginal resection was considered adequate. Multistate models were implemented with the mstate library in R. RESULTS: In multistate analysis, patients who experienced a local recurrence were more likely to have distant metastasis develop (hazard ratio [HR] = 8.4; 95% CI, 4.3-16.5; p < 0.001), and to die (HR = 3.4; 95% CI, 2.1-5.6; p < 0.001). The occurrence of distant metastasis was associated with a strong increase in the risk of death (HR = 12.6; 95% CI, 8.7-18.3; p < 0.001). Distant metastasis occurring after a long tumor-free interval was not associated with a more-favorable prognosis with respect to mortality than distant metastasis occurring early after surgery (estimated relative decrease in the adverse effect of distant metastasis on mortality for 1-year delay in the occurrence of distant metastasis = 0.9; 95% CI, 0.7-1.1; p = 0.28). High-grade histology (Grades 2 and 3) was associated with a higher risk of overall recurrence (defined as a composite of local recurrence and distant metastasis, HR = 3.8; 95% CI, 1.8-7.8; p = 0.0003) and a higher risk of death after recurrence developed (HR = 4.4; 95% CI, 1.1-18.2; p = 0.04). Finally, the multistate model predicted distinct outcome patterns depending on baseline covariates and how long a patient has remained free from recurrence after surgery. CONCLUSIONS: In patients with localized soft tissue sarcoma undergoing resection, the occurrence of local recurrence and distant metastasis contributes to a dramatically impaired long-term survival outcome. Local recurrences are a substantial risk factor for distant metastasis. Multistate modeling is a very powerful approach for analysis of sarcoma cohorts, and may be used in the future to obtain highly personalized, dynamic predictions of outcomes in patients with localized soft tissue sarcoma. LEVEL OF EVIDENCE: Level III, therapeutic study.

[GIANT CELL TUMOR OF BONE: RESULTS AND TREATMENT COMPLICATIONS]. / GIGANTOCELULARNI TUMORI KOSTI: REZULTATI I KOMPLIKACIJE LIJECENJA.

Giant cell tumor of bone (GCT) is mostly benign, locally aggressive tumor with a high recurrence rate. GCT is treated primarily surgically, and the approach is determined according to localization and local tumor behavior. The aim of this study was to analyze results and complications of surgical treatment of GCT at atertiary orthopedic clinical center in Croatia. We analyzed all patients treated at University Department of Orthopedics, Zagreb University Hospital Center, during a 15-year period. From 1995 to 2009, 39 patients were surgically treated for GCT. Four patients were lost from follow up. In patients with low-grade GCT (n = 12, 34%), we performed marginal-intralesional resection, whereas in patients with locally aggressive GCT we performed en bloc resection and reconstruction with tumor endoprosthesis or bone allograft (n = 22, 63%). In one patient, the only treatment was tumor irradiation. Complications were evident in one-third of our patients. The most common complications were tumor recurrence (n = 6, 50% of all complications) and deep infection (n = 2, 17% of all complications). We performed amputation in two patients in whom osteosarcoma was revealed under GCT radiologic and histologic appearance. We performed 84 operations in 35 patients, not counting primary biopsy. In conclusion, treatment of GCT is complex, with a high incidence of tumor recurrence. Diagnosis and treatment are best provided through a multidisciplinary approach in highly specialized centers for orthopedic oncology.

Prevalence and characteristics of benign cartilaginous tumours of the knee joint as identified on MRI scans.

BACKGROUND: Enchondromas (EC) and atypical cartilaginous tumours (ACT) of the knee joint represent benign/intermediate chondromatous neoplasms of the bone that are most commonly discovered incidentally. Based on small to intermediate-sized cohorts, the prevalence of cartilaginous tumours of the knee as visible in MRI is estimated at 0.2-2.9%. This study aimed at verifying/challenging these numbers via retrospective examination of a larger, uniform patient cohort. METHODS: Between 01.01.2007 and 01.03.2020, 44,762 patients had received an MRI of the knee for any indication at a radiologic centre. Of these, 697 patients presented with MRI reports positive for cartilaginous lesions. In a three-step workflow, 46 patients were excluded by a trained co-author, a radiologist and an orthopaedic oncologist, as wrongly being diagnosed for a cartilage tumour. RESULTS: Of 44,762 patients, 651 presented with at least one EC/ACT indicating a prevalence of 1.45% for benign/intermediate cartilaginous tumours of the knee joint (EC: 1.4%; ACTs: 0.05%). As 21 patients showed 2 chondromatous lesions, altogether 672 tumours (650 ECs [96.7%] and 22 ACTs [3.3%]) could be analysed in terms of tumour characteristics: With a mean size of 1.6 ± 1.1 cm, most lesions were located in the distal femur (72.9%), in the metaphysis of the respective bone (58.9%) and centrally in the medullary canal (57.4%). CONCLUSIONS: This study revealed an overall prevalence of 1.45% for cartilage lesions around the knee joint. Whilst a constant increase in prevalence was found for ECs over 13.2 years, prevalence remained constant for ACTs.

Prognostic Impact of Pulmonary Metastasectomy in Bone Sarcoma Patients: A Retrospective, Single-Centre Study.

This retrospective study aimed at analyzing the impact of metastasectomy on post-metastasis survival (PMS) in bone sarcoma patients with lung metastases. Altogether, 47 bone sarcoma patients (24 males, median age at diagnosis of lung metastases: 21.8 (IQR: 15.6-47.3) years) with primary (n = 8) or secondary (n = 39) lung metastases treated at a single university hospital were retrospectively included. Based on a propensity score, inverse probability of treatment weight (IPTW) was calculated to account for selection bias whether patients had undergone metastasectomy or not. The most common underlying histology was osteosarcoma (n = 37; 78.7%). Metastasectomy was performed in 39 patients (83.0%). Younger patients (p = 0.025) with singular (p = 0.043) and unilateral lesions (p = 0.024), as well as those with an interval ≥ 9 months from primary diagnosis to development of lung metastases (p = 0.024) were more likely to undergo metastasectomy. Weighted 1- and 3-year PMS after metastasectomy was 80.8% and 58.3%, compared to 88.5% and 9.1% for patients who did not undergo metastasectomy. Naive Cox-regression analysis demonstrated a significantly prolonged PMS for patients with metastasectomy (HR: 0.142; 95%CI: 0.045-0.450; p = 0.001), which was confirmed after IPTW-weighting (HR: 0.279; 95%CI: 0.118-0.662; p = 0.004), irrespective of age, time to metastasis, and the number of lesions. In conclusion, metastasectomy should be considered in bone sarcoma patients with lung metastases, after carefully considering the individual risks, to possibly improve PMS.

High complication rate with titanium plates for chest wall reconstruction following tumour resection.

OBJECTIVES: The reconstruction of the chest wall defect after tumour resection presents a challenge. Titanium rib plates were presented as a reconstruction option due to its biocompatibility, flexibility and pliability. The aim of this study was to evaluate the outcome of single-centre cohort treated with chest wall reconstruction after tumour resections, with a focus on the titanium rib plates reconstruction. METHODS: We retrospectively reviewed the data of 26 patients who underwent wide resection for malignancies of the chest wall, where reconstruction was performed using polypropylene mesh, porcine dermal collagen mesh with or without titanium rib plates, operated on between 2012 and 2019. Events being associated with the surgery requiring revision were rated as complications. RESULTS: Most of the patients had primary tumours (n = 19; 73%). A mean of 3.7 ribs (range: 1-7) was resected. Reconstruction was performed with titanium rib plates (13 patients, 50%), of these 11 were performed with additional mesh grafts. The remaining 13 patients (50%) underwent reconstruction with mesh grafts only. Fourteen patients (54%) developed a complication requiring surgical revision, after a median of 5.5 months. The most common complication was wound healing deficit (n = 4), plate fracture (n = 2), mesh rupture (n = 2), infection (n = 2) and local recurrence (n = 2). The only factor being associated with the development of complications was the usage of a plate (P = 0.015), irrespective of defect size (P = 0.29). CONCLUSIONS: The high complication rate is found when using titanium plates for chest wall reconstruction after tumour resection. A high caution is recommended in choosing the chest wall reconstruction method.

Long-term changes in serum silver concentrations after extremity reconstruction with silver-coated megaprostheses.

Silver-coated megaprostheses are considered to reduce infection rate following reconstruction of bone defects in tumour surgery or revision arthroplasty. However, little is known about systemic silver exposure and possible side effects. The aim of this study was to analyse serum silver concentrations in patients with silver-coated megaprostheses over a prolonged time period. Between 2004 and 2016, 46 patients (52.2% female, mean age at surgery 47.1 ± 24.2 years) received silver-coated megaprostheses for septic (n = 26) or oncological (n = 17; main implant since 2013) indications, or aseptic loosening (n = 3). Blood was drawn from all patients within the first few days following surgery (without silver ion levels) and thereafter every 6 months at the outpatient department (with silver ion levels). Inductively coupled plasma mass spectrometry was used to determine silver ion levels. Median follow-up was 47.3 months (IQR: 16.1-78.9). Overall, 29 revision surgeries became necessary in 20 patients, equivalent to a cumulative complication rate of 63.0%. Revisions were most commonly for periprosthetic joint infections (PJIs, n = 12) and instability/soft tissue problems (n = 10). Revision-free implant survival was 81.4%, 42.3% and 35.2% at one, 5 and 10 years. Incidence of local argyria was 8.7% (n = 4). Silver ion levels at two or more consecutive time points during follow-up were available for 26 patients. An increment of silver levels within the first months ("run-in") was observed, followed by an unspecific undulating course. Median initial and latest follow-up (median, 49.5 months) serum silver ion levels were 16.0 ppb (IQR: 9.1-29.1) and 7.4 ppb (IQR: 2.7-14.1), respectively. According to the multivariate mixed linear random-effects model, development of PJI was associated with significantly higher silver ion levels over time (p = 0.002), irrespective of time from surgery (p = 0.274). In the current series, a cumulative complication rate of 63.0% was observed for patients receiving silver-coated megaprostheses for septic of oncological indications. An overall unspecific course of silver ion concentration was present. Development of PJI was significantly associated with increased silver ion levels over time. Yet, no systemic complication associated to high silver levels occurred. It can be concluded that silver-coated implants constitute a safe solution for megaprosthetic reconstruction, but monitoring of silver concentrations is recommended.

Survival Prediction in Patients Treated Surgically for Metastases of the Appendicular Skeleton-An External Validation of 2013-SPRING Model.

INTRODUCTION: The aim of this study was to externally validate the 2013-SPRING model, a survival prediction tool for patients treated surgically for bone metastases in a retrospective patient cohort from a single institution. Moreover, subgroup analyses on patients treated with (A) endoprostheses or (B) osteosynthesis, as well as (C) upper limb and (D) lower limb metastases, were performed. METHODS: Altogether, 303 cancer patients (mean age: 67.6 ± 11.1 years; 140 males (46.2%)) with bone metastases to the extremities, treated surgically between March 2000 and June 2018 at a single tertiary sarcoma centre, were retrospectively included. Median follow-up amounted to 6.3 (interquartile range (IQR): 2.3-21.8) months, with all patients followed-up for at least one year or until death. The 2013-SPRING model was applied to assess the prognostication accuracy at 3, 6 and 12 months. Models were validated with area under the curve receiver operator characteristic (AUC ROC; the higher the better), as well as Brier score. RESULTS: Of the 303 patients, 141 had been treated with osteosynthesis (46.5%), and the remaining 162 patients with endoprosthesis (53.5%). Sixty-five (21.5%) metastases were located in the upper limbs, and two hundred and thirty-eight (78.5%) in the lower limbs. Using the 2013-SPRING model for the entire cohort, the accuracy of risk of death prediction at 3, 6 and 12 months, determined by the AUC ROC, was 0.782 (95% CI: 0.729-0.843), 0.810 (95% CI: 0.763-0.858) and 0.802 (95% CI: 0.751-0.854), respectively. Corresponding Brier scores were 0.170, 0.178 and 0.169 at 3, 6 and 12 months. In the subgroup analyses, predictive accuracy of the 2013-SPRING model was likewise encouraging, albeit being slightly higher in the osteosynthesis subgroup as compared with the endoprosthesis subgroup, and also higher in the upper limb in comparison to the lower limb metastasis subgroup. CONCLUSIONS: The current validation study of the 2013-SPRING model shows that this model is clinically relevant to use in an external cohort, also after stratification for surgical procedure and metastasis location.

Osteoid osteoma of the foot : Presentation, treatment and outcome of a multicentre cohort.

BACKGROUND: Osteoid osteomas of the foot are rare, with a varying and atypical clinical as well as radiological presentation impeding early diagnosis and treatment. The aim of the present multicentre study was to 1) analyze epidemiological, clinical and radiological findings of patients with foot osteoid osteomas and to 2) deduce a diagnostic algorithm based on the findings. METHODS: A total of 37 patients (25 males, 67.6%, mean age 23.9 years, range 8-57 years) with osteoid osteomas of the foot were retrospectively included, treated between 2000 and 2014 at 6 participating tertiary tumor centres. Radiographic images were analyzed, as were patients' minor and major complaints, pain relief and recurrence. RESULTS: Most osteoid osteomas were located in the midfoot (n = 16) and hindfoot (n = 14). Painful lesions were present in all but one patient (97.3%). Symptom duration was similar for hindfoot and midfoot/forefoot (p = 0.331). Cortical lesions required fewer x­rays for diagnosis than lesions at other sites (p = 0.026). A typical nidus could be detected in only 23/37 of x­rays (62.2%), compared to 25/29 CT scans (86.2%) and 11/22 MRIs (50%). Aspirin test was positive in 18/20 patients (90%), 31 patients (83.8%) underwent open surgery. Pain relief was achieved in 34/36 patients (outcome unknown in one), whilst pain persisted in two patients with later confirmed recurrence. CONCLUSIONS: As previously reported, CT scans seem to be superior to MRIs towards detection of the typical nidus in foot osteoid osteomas. In patients with unclear pain of the foot and inconclusive x­rays, osteoid osteoma should be considered as differential diagnosis.

Complications, mobility, and quality of life in ankle sarcoma patients.

AIMS: The aims of the study were to analyze differences in surgical and oncological outcomes, as well as quality of life (QoL) and function in patients with ankle sarcomas undergoing three forms of surgical treatment, minor or major limb salvage surgery (LSS), or amputation. METHODS: A total of 69 patients with ankle sarcomas, treated between 1981 and 2017 at two tumour centres, were retrospectively reviewed (mean age at surgery: 46.3 years (SD 22.0); 31 females (45%)). Among these 69 patients 25 were analyzed prospectively (mean age at latest follow-up: 61.2 years (SD 20.7); 11 females (44%)), and assessed for mobility using the Prosthetic Limb Users Survey of Mobility (PLUS-M; for amputees only), the Toronto Extremity Salvage Score (TESS), and the University of California, Los Angeles (UCLA) Activity Score. Individual QoL was evaluated in these 25 patients using the five-level EuroQol five-dimension (EQ-5D-5L) and Fragebogen zur Lebenszufriedenheit/Questions on Life Satisfaction (FLZ). RESULTS: Of the total number of patients in the study, 22 (32%) underwent minor LSS and 22 (32%) underwent major LSS; 25 underwent primary amputation (36%). Complications developed in 26 (38%) patients, and were more common in those with major or minor LSS in comparison to amputation (59% vs 36% vs 20%; p = 0.022). A time-dependent trend towards higher complication risk following any LSS was present (relative risk: 0.204; 95% confidence interval (CI) 0.026 to 1.614; p = 0.095). In the prospective cohort, mean TESS was higher following minor LSS in comparison to amputation (91.0 vs 67.3; p = 0.006), while there was no statistically significant difference between major LSS and amputation (81.6 vs 67.3; p = 0.099). There was no difference in mean UCLA (p = 0.334) between the three groups (p = 0.334). None of the items in FLZ or EQ-5D-5L were different between the three groups (all p > 0.05), except for FLZ item "self-relation", being lower in amputees. CONCLUSION: Complications are common following LSS for ankle sarcomas. QoL is comparable between patients with LSS or amputation, despite better mobility scores for patients following minor LSS. We conclude that these results allow a decision for amputation to be made more easily in patients particularly where the principles of oncological surgery would otherwise be at risk. Cite this article: Bone Joint J 2021;103-B(3):553-561.

Molecular profiling of soft-tissue sarcomas with FoundationOne® Heme identifies potential targets for sarcoma therapy: a single-centre experience.

BACKGROUND: Molecular diagnosis has become an established tool in the characterisation of adult soft-tissue sarcomas (STS). FoundationOne® Heme analyses somatic gene alterations in sarcomas via DNA and RNA-hotspot sequencing of tumour-associated genes. METHODS: We evaluated FoundationOne® Heme testing in 81 localised STS including 35 translocation-associated and 46 complex-karyotyped cases from a single institution. RESULTS: Although FoundationOne® Heme achieved broad patient coverage and identified at least five genetic alterations in each sample, the sensitivity for fusion detection was rather low, at 42.4%. Nevertheless, potential targets for STS treatment were detected using the FoundationOne® Heme assay: complex-karyotyped sarcomas frequently displayed copy-number alterations of common tumour-suppressor genes, particularly deletions in TP53, NF1, ATRX, and CDKN2A. A subset of myxofibrosarcomas (MFS) was amplified for HGF (n = 3) and MET (n = 1). PIK3CA was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%). Epigenetic regulators (e.g. MLL2 and MLL3) were frequently mutated. CONCLUSIONS: In summary, FoundationOne® Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. HGF/MET in a subset of MFS, or PIK3CA in MLS). The assay's sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort.