Do Patients Treated With an Unplanned Resection for Small Superficial Soft Tissue Sarcomas Have Worse Long-term Survival Than Those Initially Treated With an Oncologic Resection?

BACKGROUND: Histologic grade, size, and depth are well-known prognostic factors in soft tissue sarcomas (STS). Small (< 5 cm) and superficial STS generally have an excellent prognosis when treated with appropriate surgery. However, they are often misdiagnosed and mistreated. We reported that in midterm follow-up (5 to 7 years), patients with unplanned resections of tumors with positive margins who immediately underwent a reoperation with margin-widening re-resection and postoperative radiotherapy had survival comparable to that of patients who were initially treated correctly. In that article, we included STS larger than 5 cm, deep STS, and individuals with local recurrence. However, we wanted to evaluate the impact of unplanned resection on the survival of patients who had STS with the best prognosis, small and superficial STS, with two groups that were as homogeneous as possible. QUESTION/PURPOSE: Do patients with small and superficial STS who underwent an unplanned resection have worse prognosis in the long term than those who were initially treated correctly? METHODS: We exclusively evaluated patients with small (< 5 cm) and superficial (to the deep fascia) STS. We systematically excluded deep STS. Among this subset, we identified 93 patients with superficial STS. We excluded patients with local relapse, metastatic disease, superficial STS of the head or neck, those with insufficient clinical or dosimetric information, and patients with follow-up of less than 2 years. Furthermore, our focus on investigating the most benign and homogeneous STS prompted us to exclude patients with superficial tumors greater than or equal to 5 cm. This selection was driven by the presumed better prognosis associated with smaller tumors, inevitably leading to a smaller pool of patients for direct comparison with patients who had unplanned resections. The initial expectation was to observe similar survival outcomes between cohorts. Between 1990 and 2019, a total of 17 patients underwent surgical treatment at our private, medium-size center. Of those, 29% (5 patients) were lost to follow-up before 2 years without meeting a study endpoint (relapse, metastasis or revision, reoperation, or death), leaving a total of 71% (12 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with surgery alone. During that same period, another 51 patients were referred to us after undergoing an unplanned resection of a lesion that subsequently was determined to be a soft tissue malignancy. Of those, 18% (9 patients) were lost to follow-up before 2 years without meeting a study endpoint, leaving 82% (42 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with re-excision and postoperative radiotherapy. Patients with unplanned resections had an older mean age (51± 5 versus 44 ± 7 years; p = 0.1) and a higher proportion of female patients (58% versus 38%; p = 0.07), but the groups did not differ in terms of largest diameter, histologic type, or tumor location. However, patients with planned resections had a higher proportion of high-grade STS (75% versus 55%; p = 0.07). No metastases were present in either group at diagnosis. We performed a univariate analysis of the groups. We could not perform a multivariate analysis because of the small sample. We compared the groups in terms of local recurrence and all-cause mortality using the Kaplan-Meier survivorship estimator. RESULTS: According to the Kaplan-Meier survivorship estimator, survivorship free from local recurrence at a mean of 20 years of follow-up was better in the planned resection group than in the unplanned resection group (92% [95% CI 63% to 100%] versus 69% [95% CI 54% to 81%]; p = 0.04). Furthermore, overall survivorship at 5 years was higher in the planned resection group than in the unplanned resection group (100% [95% CI 72% to 100%] versus 70% [95% CI 54% to 81%]; p = 0.04). Similarly, the planned resection group exhibited superior survivorship at 20 years of follow-up (100% [95% CI 72% to 100%] versus 62% [95% CI 47% to 75%]; p = 0.01). Metastatic disease was absent in the planned resection group, while it occurred in 12 patients in the unplanned resection group (28% [95% CI 17% to 44%]). CONCLUSION: Unplanned resection for patients with small and superficial STS was associated with a decrease in overall survival in the long term, despite the use of postoperative radiotherapy. An unplanned resection may be an important prognostic factor. Nevertheless, larger and prospective studies are needed to validate our findings. Although small and superficial lumps are usually benign, nonsarcoma surgeons should be aware that some masses may be malignant, and if in doubt, MR imaging, a biopsy before excision, or consultation with or referral to a sarcoma center should be considered before removing the mass. LEVEL OF EVIDENCE: Level III, therapeutic study.

Incidence and risk factors for stroke after hip fracture: a meta-analysis.

Hip fractures represent a high burden and are associated with mortality in up to 30% of the cases. Stroke complications can be devastating and increase mortality and disability in elderly patients. This study aimed to determine the overall incidence and risk factors for stroke in patients with hip fractures. A systematic search of the literature using PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases was carried out. Studies have reported the incidence of stroke in patients > 50 years of age with hip fractures. Data were extracted according to PRISMA guidelines (PROSPERO: CRD42023384742). Data were combined using Review Manager version 5.4. A random-effects model was adopted if a significant heterogeneity was observed. The primary outcome was the incidence of stroke in patients with hip fractures. The secondary outcomes of interest included the influence on the incidence of demographic factors, associated conditions, habits, and analytical parameters. Of the 635 initially retrieved studies, 18 were included, with 256,197 patients. The mean age of the patients ranged from 55 to 84 years old. The overall incidence of stroke in patients with hip fracture was 6.72% (95% CI 4.37-9.07%. The incidence of stroke by region was highest in the American continent (8.09%, 95% CI 3.60-12.58%; P > 0.001). Regarding associated conditions diabetes significantly increased the risk of stroke (OR 1.80, 95% CI 1.41-2.30). Respect to patient characteristics, BMI greater than 24.4 and female gender did not significantly increase the risk of stroke: (OR 1.07, 95% CI 0.74-1.56) and (OR 1.15, 95% CI 0.91-1.46). Lastly, lower albumin concentrations were a risk factor for stroke in patients with hip fracture (MD - 3.18, 95% CI - 4.06 to 2.31). In conclusion, the incidence of stroke after hip fracture was 6.72%. The incidence of stroke increases over time, and the closely associated risk factors are diabetes and low albumin level.

Efficacy and safety of arthroscopy in femoroacetabular impingement syndrome: a systematic review and meta-analysis of randomized clinical trials.

This study aimed to compare the efficacy and safety of arthroscopy with physiotherapy or joint lavage in patients with femoroacetabular impingement (FAI). A meta-analysis using PubMed, Embase, Scopus, and the Cochrane Collaboration Library databases was performed in September 2022. We included studies focusing on patients with FAI who underwent arthroscopic surgery versus those who underwent physiotherapy or arthroscopic lavage. The outcomes were functional scores (iHOT-33 and HOS ADL) and adverse events. Randomized clinical trials were included in the study. The risk of bias in each study was assessed according to Cochrane guidelines for clinical trials. The data were combined using Review Manager version 5.4. (PROSPERO CRD42022375273). Six RCTs were included, from a pool of 839 patients (407 females). The iHOT-33 and HOS ADL scales showed significant differences at 12 months in favor of the arthroscopy group (MD, 10.65; 95% CI 6.54-4.76) and (MD, 8.09; 95% CI 3.11-13.07). MCID was not achieved through arthroscopy in functional variables. The rates of osteoarthritis (OR, 6.18; 95% CI 1.06-36.00) and numbness (OR, 73.73; 95% CI 10.00-43.92) were significantly higher in the arthroscopy group. Arthroscopic surgery showed statistical superiority over the control group without exceeding the MCID in most studies; however, the results might have been influenced by secondary variables. Finally, arthroscopic surgery results in a high rate of conversion to osteoarthritis.

Femoroacetabular Impingement and the Effect of Osteochondroplasty on Hip Osteoarthritis Prevention: The Pandora's Box Opening Process.

OBJECTIVE: This study was conducted to assess the effect of osteochondroplasty on osteoarthritis (OA) prevention, comparing radiological evolution between identical hips from the same patient who had undergone unilateral surgery. DESIGN: We retrospectively reviewed radiological evolution between hips with similar shape from the same patient who had undergone unilateral surgery. In all, 56 FAI patients (112 hips) with a mean age of 42.18 ± 9.16 years and had undergone unilateral arthroscopy treatment have been included. Four independent researchers measured Wiberg, Acetabular and Alpha angles, Extrusion index, and Tönnis classification preoperatively to verify that operated and non-operated hips had the same shape. OA evolution was assessed by joint space width (JSW) in 3 different articular points and Tönnis classification. RESULTS: No preoperative anatomical differences were present between groups (P > 0.05). At the end of follow-up (31.9 months), a decrease of JSW in the 3 points measured was found in OP hips (OP vs. N-OP; P < 0.01). These results were correlated with changes in the proportion of patients who progressed to grade III in Tönnis classification (from 1.3% preoperative to 23.2% at the end of follow-up). CONCLUSIONS: Osteochondroplasty and labrum procedures were not associated with OA prevention. The OP hips showed a faster OA degeneration, which was not seen in the N-OP. These results will encourage hip surgeons to perform further investigations to avoid the "Pandora's Box Opening Process."

Epiphyseal distraction prior to resection in paediatric bone sarcomas : four decades of experience.

Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Cañadell's technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Cañadell's work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.Cite this article: Bone Joint J 2023;105-B(1):11-16.

Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single-cell resolution.

Early hematopoiesis is a continuous process in which hematopoietic stem and progenitor cells (HSPCs) gradually differentiate toward specific lineages. Aging and myeloid malignant transformation are characterized by changes in the composition and regulation of HSPCs. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize an enriched population of human HSPCs obtained from young and elderly healthy individuals.Based on their transcriptional profile, we identified changes in the proportions of progenitor compartments during aging, and differences in their functionality, as evidenced by gene set enrichment analysis. Trajectory inference revealed that altered gene expression dynamics accompanied cell differentiation, which could explain aging-associated changes in hematopoiesis. Next, we focused on key regulators of transcription by constructing gene regulatory networks (GRNs) and detected regulons that were specifically active in elderly individuals. Using previous findings in healthy cells as a reference, we analyzed scRNA-seq data obtained from patients with myelodysplastic syndrome (MDS) and detected specific alterations of the expression dynamics of genes involved in erythroid differentiation in all patients with MDS such as TRIB2. In addition, the comparison between transcriptional programs and GRNs regulating normal HSPCs and MDS HSPCs allowed identification of regulons that were specifically active in MDS cases such as SMAD1, HOXA6, POU2F2, and RUNX1 suggesting a role of these transcription factors (TFs) in the pathogenesis of the disease.In summary, we demonstrate that the combination of single-cell technologies with computational analysis tools enable the study of a variety of cellular mechanisms involved in complex biological systems such as early hematopoiesis and can be used to dissect perturbed differentiation trajectories associated with perturbations such as aging and malignant transformation. Furthermore, the identification of abnormal regulatory mechanisms associated with myeloid malignancies could be exploited for personalized therapeutic approaches in individual patients.

Our blood contains many different types of cells; red blood cells carry oxygen through the body, platelets help to stop bleeding and a variety of white blood cells fight infections. All of these critical components come from a pool of immature cells in bone marrow, which can develop and specialise into any of these. However, as we get older, these immature cells can accumulate damage, including mutations in specific genes. This increases the risk of diseases such as myelodysplastic syndromes (MDS), a type of cancer in which the cells cannot develop and the patient does not have enough healthy mature blood cells. The changes in gene activity in the immature cells have previously been studied using samples from young and elderly people, as well as individuals with MDS. These studies examined large numbers of cells together, revealing differences between young and elderly people, and individuals with MDS. However, this does not describe how the different types alter their behaviour. To address this, Ainciburu, Ezponda et al. used a technique called single-cell RNA sequencing to study the gene activity in individual immature blood cells. This revealed changes associated with maturation that may account for the different combinations of cell populations in younger and older people. The results confirmed findings from previous studies and suggested new genes involved in ageing or MDS. Ainciburu, Ezponda et al. used these results to create an analytical system that highlights gene activity differences in individual MDS patients that are independent of age-related changes. These results provide new insights that could help further research into the development of MDS and the ageing process. In addition, scientists could study other diseases using this approach of analysing individual patients' gene activity. In future, this could help to personalise clinical decisions on diagnosis and treatment.

The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in older individuals. Here we analyze the transcriptome of human HSCs purified from young and older healthy adults, as well as MDS patients, identifying transcriptional alterations following different patterns of expression. While aging-associated lesions seem to predispose HSCs to myeloid transformation, disease-specific alterations may trigger MDS development. Among MDS-specific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthy HSCs induces an MDS-like transcriptional state, and dyserythropoiesis, an effect associated with a failure in the activation of transcriptional programs required for normal erythroid differentiation. Moreover, DDIT3 knockdown in CD34+ cells from MDS patients with anemia is able to restore erythropoiesis. These results identify DDIT3 as a driver of dyserythropoiesis, and a potential therapeutic target to restore the inefficient erythroid differentiation characterizing MDS patients.

Hip Preservation Surgery in Osteoarthritis Prevention: Potential Benefits of the Radiographic Angular Correction.

Objective: The aim of the study is to describe the morphology associated with the development of osteoarthritis (OA) in three different age groups. These data will contribute to defining the morphology associated with early and late hip OA. Methods: We studied 400 hips in 377 patients who had undergone primary THA due to idiopathic OA. Three groups were compared: group 1 (n = 147), younger patients, aged up to 60 years; group 2 (n = 155), patients aged between 61 and 74 years; and group 3 (n = 98), aged 75 or over. Five independent researchers measured the hip angles and the mean values were used to build a database. Results: No differences between groups in sex distribution and BMI were detected. Less coverage of the head (extrusion index), higher Tönnis angle, lower Wiberg and alpha angles characterized early OA hips. These differences increased with age, being greater between group 2 and group 3 (p < 0.01). However, significant differences were still present in the comparison between group 1 and group 2 (p < 0.01)). No differences were detected between group 2 and group 3. Conclusion: Elevated acetabular angle, head extrusion and decreased Wiberg angle characterize hip osteoarthritis at younger ages and should be the focus of hip preservation surgery in terms of osteoarthritis prevention. Pincer-type FAI (higher Wiberg and lower Tönnis angle) and higher alpha angle (CAM) are correlated with the development of later OA. These results shed doubt on applying the hip preservation surgery concept in terms of osteoarthritis prevention in FAI, especially in Pincer-type FAI patients.

P144 a Transforming Growth Factor Beta Inhibitor Peptide, Generates Antifibrogenic Effects in a Radiotherapy Induced Fibrosis Model.

Radiation-induced fibrosis (RIF) is a severe side effect related with soft tissues sarcomas (STS) radiotherapy. RIF is a multicellular process initiated primarily by TGF-ß1 that is increased in irradiated tissue, whose signaling leads to intracellular Smad2/3 phosphorylation and further induction of profibrotic target genes. P144 (Disetertide©) is a peptide inhibitor of TGF-ß1 and is proposed as a candidate compound for reducing RIF associated wound healing problems and muscle fibrosis in STS. METHODS: A treatment and control group of WNZ rabbits were employed to implement a brachytherapy animal model, through catheter implantation at the lower limb. Two days after implantation, animals received 20 Gy isodosis, intended to induce a high RIF grade. The treatment group received intravenous P144 administration following a brachytherapy session, repeated at 24-72 h post-radiation, while the control group received placebo. Four weeks later, affected muscular tissues underwent histological processing for collagen quantification and P-Smad2/3 immunohistochemistry through image analysis. RESULTS: High isodosis Brachytherapy produced remarkable fibrosis in this experimental model. Results showed retained macro and microscopical morphology of muscle in the P144 treated group, with reduced extracellular matrix fibrosis, with a lower area of collagen deposition measured through Masson's trichrome staining. Intravenous P144 also induced a significant reduction in Smad2/3 phosphorylation levels compared with the placebo group. CONCLUSIONS: P144 administration clearly reduces RIF and opens a new potential co-treatment approach to reduce complications in soft tissue sarcoma (STS) radiotherapy. Further studies are required to establish whether the dosage and timing optimization of P144 administration, in different RIF phases, might entirely avoid fibrosis associated with STS brachytherapy.

What Do We Know about Survival in Skeletally Premature Children Aged 0 to 10 Years with Ewing Sarcoma? A Multicenter 10-Year Follow-Up Study in 60 Patients.

(1) Background: Younger age has been associated with better overall survival (OS) in Ewing sarcoma (ES), especially under the age of 10. The favorable survival in younger patients underlines the need for minimizing treatment burden and late sequelae. Our study aimed at describing clinical characteristics, treatment and outcome of a cohort of ES patients aged 0−10. (2) Methods: In this retrospective multicenter study, all consecutive ES patients aged 0−10, treated in four sarcoma centers in the Netherlands (n = 33) and one in Spain (n = 27) between 1982 and 2008, with a minimum follow-up of 10 years, were included. OS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were calculated. Potential factors of influence on OS (risk and protective factors) were analyzed. (3) Results: 60 patients with median follow-up 13.03 years were included. All patients were treated with chemotherapy in combination with local treatment, being surgery alone in 30 (50%) patients, radiotherapy (RT) alone in 12 (20%) patients or surgery plus RT in 18 (30%) patients (12 pre- and 6 postoperative). Limb salvage was achieved in 93% of patients. The 10-OS, -LRFS and -DMFS are 81% (95% CI: 71−91%), 89% (95% CI: 85−93%) and 81% (95% CI: 71−91%), respectively. Six patients developed LR, of which two developed subsequent DM; all had axial ES (pelvis, spine or chest wall), and these patients all died. Ten patients developed DM; eight died due to progressive disease, and two are currently in remission, both with pulmonary metastasis only. Negative or wide resection margin was significantly associated with better OS. Age < 6 years, tumor volume < 200 mL, absence of metastatic disease and treatment after 2000 showed trends towards better OS. Two patients developed secondary malignancy; both had chemotherapy combined with definitive RT for local treatment. (4) Conclusions: Overall survival of these youngest patients with ES was very good. Limb salvage surgery was achieved in >90% of patients. Wide resection margin was the only factor significantly associated with better survival.

Dose volume histogram constraints in patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative HDR brachytherapy.

BACKGROUND: Wound healing complications (WHC), osteoradionecrosis (ORN), and nerve damage (ND) are common adverse effects in adult patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative high dose rate brachytherapy (PHDRB) alone or combined with external beam radiotherapy (EBRT). RATIONALE: Analysis of the treatment factors contributing to these complications can potentially minimize their occurrence and severity. PATIENTS: A total of 169 patients enrolled in two parallel prospective studies were included in this analysis. Previously Unirradiated cases (Group 1; n = 139) were treated with surgical resection, 16-24 Gy of PHDRB and 45 Gy of EBRT. Adjuvant chemotherapy was given to selected patients with high-grade tumors. Previously irradiated cases (Group 2; n = 30) were treated with surgical resection and 32-40 Gy of PHDRB without further EBRT. METHODS: Patient factors, tumor factors, surgical factors, PHDRB factors and EBRT factors were analyzed using Cox univariate and multivariate analysis. RESULTS: In Previously Unirradiated cases, WHC, ORN and ND occurred in 38.8%, 5.0% and 19.4%. Multivariate analysis indicated that WHC increased with CTV size (p = 0.02) and CTV2cm3 Physical dose (p = 0.02). ORN increased with Bone2cm3 EQD2 ≥ 67 Gy(p = 0.01) and ND was more frequent in patients with TV100DVH-based dose (tissue volume encompassed by the 100% isodose) ≥ 84 Gy (p < 0.01). In Previously Irradiated cases, WHC, ORN and ND occurred in 63.3%, 3.3% and 23.3%. Multivariate analysis showed that WHC was more frequent in patients with Skin2cm3Lifetime EQD2 ≥ 84 Gy (p = 0.01) and ND was more frequent after CTVD90 Physical Doses ≥ 40 Gy (p < 0.01). CONCLUSIONS: WHC in Previously Unirradiated patients can be minimized by using a more conservative CTV definition together with a meticulous implant technique and planning aimed to minimize hyperdose CTV2cm3 areas. In Previously Irradiated patients WHC may be mimimized considering Lifetime EQD2 Skin2cm3 doses. ORN can be reduced by using the Bone2cm3 EQD2 constraint. ND occurs more frequently in patients with large tumors receiving high treated volume doses, but no specific constraints can be recommended due to the lack of peripheral nerve definition during brachytherapy planning.

A Reassessment of the Barrier Effect of the Physis against Metaphyseal Osteosarcoma: A Comprehensive Pathological Study with Its Radiological and Clinical Follow-Up Correlations.

Osteosarcoma is a primary malignant bone tumor usually arising at the metaphysis of long bones, particularly around the knee. The physis has been regarded as a barrier capable of blocking tumor extension, thus allowing it to preserve their epiphysis and therefore improve functional results. With the objective of clarifying how effective the physis is as a barrier to tumor spread, a large series of skeletally immature patients with osteosarcoma were reviewed. From 452 metaphyseal osteosarcomas a selection of 282 cases in which the tumor was close or crossing the physis were carried out. This sub-sample was split into two groups according to the surgical treatment (epiphyseal preservation or not). The specimens obtained by resection were studied, and the physeal and metaphyseal areas were studied by multiple sections. Immunostaining against VEGF of physis was obtained in selected cases. In about half of the patients affected by metaphyseal malignant bone tumors, the growth plate and epiphysis were not compromised by the tumor. Three sequential invasive growth patterns of an osteosarcoma in its relationship with the physis could be distinguished. An intense angiogenesis and osteoclastic reaction could be observed in the growth plate in the free zone between the tumor and the physis. The local recurrence incidence was lower in the epiphyseal preservation treated patients than it was in the conventional treatment (8% vs. 12%). Most local recurrences appeared in the first 2 years. The overall survival of patients treated with epiphyseal preservation was better than that of the patients treated without preserving the epiphysis (73% vs. 59%; p = 0.03) at a mean follow-up of 18 years. We have described an angiogenic and osteoclastic reaction in the base of the growth plate in the proximity of the advance front of the tumor, which could facilitate the osteosarcoma invasion. It is also shown that the preoperative imaging method for examination is a valid approach for the decision to carry out epiphyseal preservation. Finally, we concluded that epiphyseal preservation combined with protective chemotherapy is an excellent clinical approach for selected patients with metaphyseal osteosarcoma.

Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas.

Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing's sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.

Biology and technology in the surgical treatment of malignant bone tumours in children and adolescents, with a special note on the very young.

PURPOSE: The main challenge in reconstruction after malignant bone tumour resection in young children remains how and when growth-plates can be preserved and which options remain if impossible. METHODS: We describe different strategies to assure best possible long-term function for young children undergoing resection of malignant bone tumours. RESULTS: Different resources are available to treat children with malignant bones tumours: a) preoperative planning simulates scenarios for tumour resection and limb reconstruction, facilitating decision-making for surgical and reconstructive techniques in individual patients; b) allograft reconstruction offers bone-stock preservation for future needs. Most allografts are intact at long-term follow-up, but limb-length inequalities and corrective/revision surgery are common in young patients; c) free vascularized fibula can be used as stand-alone reconstruction, vascularized augmentation of structural allograft or devitalized autograft. Longitudinal growth and joint remodelling potential can be preserved, if transferred with vascularized proximal physis; d) epiphysiolysis before resection with continuous physeal distraction provides safe resection margins and maintains growth-plate and epiphysis; e) 3D printing may facilitate joint salvage by reconstruction with patient-specific instruments. Very short stems can be created for fixation in (epi-)metaphysis, preserving native joints; f) growing endoprosthesis can provide for remaining growth after resection of epi-metaphyseal tumours. At ten-year follow-up, limb survival was 89%, but multiple surgeries are often required; g) rotationplasty and amputation should be considered if limb salvage is impossible and/or would result in decreased function and quality of life. CONCLUSION: Several biological and technological reconstruction options must be merged and used to yield best outcomes when treating young children with malignant bone tumours. LEVEL OF EVIDENCE: Level V Expert opinion.

Cemented Dual Mobility Cup for Primary Total Hip Arthroplasty in Elder Patients with High-Risk Instability.

Several studies have shown that double mobility (DM) cups reduce postoperative dislocations. Does the cemented dual mobility cup reduce dislocations in a specific cohort of elder patients with a high dislocation risk? Our hypothesis is that this implant is optimal for elder patients because it reduces early dislocation. We have retrospectively reviewed elder patients who underwent total hip arthroplasty (THA) with cemented double mobility cup between March 2009 and January 2018. The inclusion criteria were patients (>75 years) who were operated on for primary THA (osteoarthritis or necrosis) with a cemented dual mobility cup and a high-risk instability (at least two patient-dependent risk factors for instability). The exclusion criteria were revision surgeries or hip fracture. In all the cases, the same surgical approach was performed with a Watson Jones modified approach in supine position. We have collected demographic data, instability risk factors. Patients were classified using the Devane's score, Merle d'Aubigné score and the patient's likelihood of falling with the Morse Fall Scale. Surgical and follow-up complications were collected from their medical history. Sixty-eight arthroplasties (68 patients) were included in the study. The median age was 81.7 years (SD 6.4), and the American Society of Anesthesiologists (ASA) score showed a distribution: II 27.94%, III 63.24% and IV 8.82%. Devane's score was less than five in all of the cases. At least two patient-dependent risk factors for instability (87% had three or more) were present in each case. The median follow-up time was 49.04 months (SD 22.6). Complications observed were two cases of infection and one case of aseptic loosening at 15 months which required revision surgery. We did not observe any prosthetic dislocation. The cemented dual mobility cup is an excellent surgical option on primary total hip arthroplasties for elder patients with high-risk instability.

Osteoid osteoma in the ankle and foot. An overview of 50 years of experience.

BACKGROUND: The literature published about osteoid osteoma (OO) in the ankle-foot consists mainly on case reports. METHODS: We performed a retrospective study in which we analyzed demographic parameters, pain characteristics, treatment options and functional outcomes measured using the AOFAS and the SEFAS scales. RESULTS: We treated 17 patients with OO around the ankle-foot. Eighty-eight percent of patients had night pain that was relieved with NSAIDs. The bones most often affected were the talus and calcaneus. OO was diagnosed 21 months after the onset of symptoms. Mean follow-up was 17.3 years. The surgical techniques most used were curettage and curettage and bone grafting. There was a significant increase in AOFAS and SEFAS scores after surgery. CONCLUSIONS: Suspicion is the base of a prompt and a correct diagnosis of OO. The OO should be especially suspected in patients who present night pain that can be relieved with NSAIDs.

Somatic and germline analysis of a familial Rothmund-Thomson syndrome in two siblings with osteosarcoma.

Rothmund-Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted.

Long-term results of Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiation in adult patients with soft tissue sarcomas of the extremities and the superficial trunk: Final results of a prospective controlled study.

BACKGROUND: To analyze toxicity, patterns of failure, and survival in 106 adult patients with soft tissue sarcomas of the extremity and the superficial trunk treated in a prospective controlled trial of combined Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiotherapy (EBRT). METHODS: Patients were treated with surgical resection and 16 Gy or 24 Gy of PHDRB for negative or close/positive margins, respectively. EBRT (45 Gy) was added postoperatively. Adjuvant chemotherapy was given to selected patients with high-grade tumors. RESULTS: The median follow-up was 7.1 years (range, 0.6-16.0). Grade ≥3 adverse events were observed in 22 patients (20.8%), and grade ≥4 events in 14 patients (13.2%). No grade 5 events were noted. Multivariate analysis (p = 0.003) found that Grade ≥3 toxic events increased with increasing implant volume (TV100). Local control, locoregional control, and distant control rates at 5 and 10 years were 89% and 87%, 82% and 80% and 75% and 69%, respectively. Multivariate analysis (p = 0.024) found that positive margins correlated with decreased local control. Disease-free survival and overall survival rates at 5 and 10 years were 64% and 59% and 73% and 62%, respectively. In multivariate analysis, disease-free survival rates decreased with increasing tumor size (p = 0.0001) and inadequate margins (p = 0.024), and overall survival decreased with increasing tumor size (p = 0.001) and male gender (p = 0.039). CONCLUSIONS: The combination of conservative surgery, high-dose PHDRB, and EBRT produces adequate function and local control in the majority of patients with soft tissue sarcomas of the extremities and the superficial trunk, including a substantial percentage of cases with positive margins. Patients with larger tumors are at a higher risk of complications, treatment failure, and cancer-related death and require an individualized treatment approach.