Improved Metastatic-Free Survival after Systematic Re-Excision Following Complete Macroscopic Unplanned Excision of Limb or Trunk Soft Tissue Sarcoma.

BACKGROUND: Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) performed out of a NETSARC reference center or after second resection was further investigated. METHODS: This large nationwide series used data from patients having experienced UE outside of a reference center from 2010 to 2019, collected in a French nationwide exhaustive prospective cohort NETSARC. Patient characteristics and survival distributions in patients reexcised (RE) or not (No-RE) are reported. Multivariate Cox proportional hazard model was conducted to adjust for classical prognosis factors. Subgroup analysis were performed to identify which patients may benefit from RE. RESULTS: Out of 2371 patients with UE for STS performed outside NETSARC reference centers, 1692 patients were not reviewed by multidisciplinary board before treatment decision and had a second operation documented. Among them, 913 patients experienced re-excision, and 779 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, size, depth, grade and histotype in patients re-excised (RE) or not (No-RE). In univariate analysis, final R0 margins are associated with a better MFS, patients with R1 margins documented at first surgery had a better MFS as compared to patients with first R0 resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53-0.93; p = 0.013). All subgroups except older patients (>70 years) and patients with large tumors (>10 cm) had superior MFS with RE. CONCLUSIONS: RE might be considered in patients with STS of limb or trunk, with UE with macroscopic complete resection performed out of a reference center, and also in originally defined R0 margin resections, to improve LRFS and MFS. Systematic RE should not be advocated for patients older than 70 years, or with tumors greater than 10 cm.

Overall survival in patients with re-excision of positive microscopic margins of limb and trunk wall soft tissue sarcoma operated outside of a reference center: a nationwide cohort analysis.

BACKGROUND: This French nationwide NETSARC exhaustive prospective cohort aims to explore the impact of systematic re-excision (RE) as adjuvant care on overall survival (OS), local recurrence free survival (LRFS), and local and distant control (RFS) in patients with soft tissue sarcoma (STS) with positive microscopic margins (R1) after initial resection performed outside of a reference center. METHODS: Eligible patients had experienced STS surgery outside a reference center from 2010 to 2017, and had R1 margins after initial surgery. Characteristics and treatment comparisons used chi-square for categorical variables and Kruskall-Wallis test for continuous data. Survival distributions were compared in patients reexcised (RE) or not (No-RE) using a log-rank test. A Cox proportional hazard model was used for subgroup analysis. RESULTS: A total of 1,284 patients had experienced initial STS surgery outside NETSARC with R1 margins, including 1,029 patients with second operation documented. Among the latter, 698 patients experienced re-excision, and 331 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, tumor size, tumor depth, and histotype in the population of patients re-excised (RE) or not (No-RE). The study identified RE as an independent favorable factor for OS (HR 0.36, 95%CI 0.23-0.56, p<0.0001), for LRFS (HR 0.45, 95%CI 0.36-0.56, p<0.0001), and for RFS (HR 0.35, 95%CI 0.26-0.46, p<0.0001). CONCLUSION: This large nationwide series shows that RE improved overall survival in patients with STS of extremities and trunk wall, with prior R1 resection performed outside of a reference center. RE as part of adjuvant care should be systematically considered.

Osteoid Osteoma: Percutaneous CT-guided Cryoablation Is a Safe, Effective, and Durable Treatment Option in Adults.

Background Cryoablation is playing an increasing role in the percutaneous treatment of bone tumors. However, despite its potential advantages over heat-based ablation techniques, the clinical safety and efficacy of cryoablation have not been established for osteoid osteoma treatment. Purpose To evaluate percutaneous CT-guided cryoablation for the treatment of osteoid osteoma in young patients and adults. Materials and Methods This retrospective study reviewed data from 50 consecutive patients who underwent percutaneous CT-guided cryoablation for the treatment of osteoid osteoma between January 2013 and June 2019 in a single institution. In 30 of 50 patients (60%), the procedure was carried out with the patient under local anesthesia and conscious sedation, with the cryoprobe covering the lesion from an extraosseous position, avoiding direct penetration of the nidus. Clinical and radiologic features, procedure-related data, visual analog scale (VAS) pain scores, complications, and overall success rate were evaluated. Statistical analyses were performed by using the nonparametric Friedman test and Wilcoxon signed rank test for repeated measures. Results Fifty patients (median age, 24 years; interquartile range [IQR], 19-38 years; 31 men) underwent CT-guided cryoablation for the treatment of osteoid osteoma, with a 96% (48 of 50 patients) overall clinical success rate. Of the two patients without clinical success, one patient had incomplete pain relief and the other experienced a recurrence of osteoid osteoma at 11 months, which was successfully treated with a second cryoablation procedure. The median VAS pain score was 8 (IQR, 7-8) before the procedure and 0 (IQR, 0-1; P < .001) after the procedure at both primary (6 weeks) and secondary (18-90 months) follow-up. Three of the 50 patients had minor complications (6%); no major complications were reported. Conclusion Osteoid osteoma was safely, effectively, and durably treated with CT-guided percutaneous cryoablation. In the majority of patients, treatment could be performed without general anesthesia, with the cryosphere covering the nidus from an extraosseous position. © RSNA, 2021.

Does screwless scarf osteotomy for hallux valgus increase the risk of transfer metatarsalgia?

INTRODUCTION: The scarf osteotomy is a reliable surgical technique for treating hallux valgus. The aim of our study was to analyze the occurrence of transfer metatarsalgia after surgery on the first ray using a screwless Scarf osteotomy technique that we have been using in our department since 1995, which consists of stabilization by axial impaction without internal fixation. We hypothesized that the alleged shortening of the first metatarsal produced by this technique may be at the origin of postoperative metatarsalgia. PATIENTS AND METHODS: This was a case series of first ray metatarsal screwless Scarf osteotomies reviewed in the medium term. We did a clinical and radiological review of all patients operated using this technique between 2012 and 2017 who did not meet the following exclusion criteria: procedure on the other lateral metatarsals, concurrent hindfoot pathology, incomplete medical records. RESULTS: Of 114 feet, 96 were included in the study and 18 were excluded. The mean follow-up was 1 year and 8 months [1-4years]. The mean AOFAS score was 90.3 and 96% of patients were either satisfied or very satisfied with the outcome. All the parameters improved significantly: shoe wearing, pain, function, alignment. Fourteen feet had transfer metatarsalgia, which appeared during the first year postoperative (AOFAS 75/100). Ten other complications occurred: two Morton's neuromas, three cases of complex regional pain syndrome, one superficial infection, one paresthesia, two recurrences with surgical revision, one nonunion. No general complications were found. Based on radiographs, the mean M1 shortening was 3.3mm (6.3mm in metatarsalgia group versus 3.0 mm in the non-metatarsalgia group, P=0.2) and the mean angular correction was 16.2° (±6°). DISCUSSION: The overall results of screwless Scarf osteotomy are comparable and satisfactory, allowing large deformities to be corrected (28°±8° preoperatively in our cohort). M1 shortening and the transfer metatarsalgia rate appear to be higher than with other techniques. CONCLUSION: Screwless scarf osteotomy of M1 yields good functional and radiological outcomes in the medium term. However, it appears to cause more shortening and transfer metatarsalgia. LEVEL OF EVIDENCE: IV Retrospective, non-interventional in current practice (Recommendation grade C, low level of scientific proof).

Fixed-hinge cemented modular implants: An effective reconstruction technique following primary distal femoral bone tumor resection. A 136-case multicenter series.

BACKGROUND: Reconstruction by endoprosthesis is widespread after bone tumor resection. The design and type of fixation and of hinge remain a matter of debate. The aim of the present study was to assess survival, complications and functional results in a homogeneous series of adult patients undergoing bone defect reconstruction following distal femoral tumor resection, using a single model of fixed-hinge cemented endoprosthesis, at a minimum 5 years' follow-up. HYPOTHESIS: The study hypotheses were that loosening and infection are the main causes of failure, and that this type of reconstruction is reliable following distal femoral resection. PATIENTS AND METHODS: All patients aged over 17 years undergoing reconstruction using the Stanmore Mets® fixed-hinge cemented modular endoprosthesis following distal femoral resection for primary bone tumor in 4 French reference centers between 2004 and 2013 were included. Epidemiological data, MSTS functional score, clinical and radiological examination results, complications and survival with types of failure according to the Henderson classification were assessed. RESULTS: One hundred and thirty-six patients (68 male, 68 female; mean age, 41.2 years [range, 17-77 years]) were included. Mean follow-up was 81 months [range, 61-134 months]. Thirty-two patients (38%) experienced a total 67 complications requiring surgical revision: mainly infection (n=28) or mechanical failure (n=26). Overall implant survival was 78% at 5 years. There were 30 implant failures on the Henderson classification. Mean MSTS score was 82%. DISCUSSION: The present results are comparable to those of the literature and for other types of reconstruction. Recent meta-analyses suggest that type of hinge and of stem fixation have little effect on implant survival. International comparative studies are needed to determine the exact role of each type of reconstruction according to the patient profile. LEVEL OF EVIDENCE: IV, multicenter retrospective series.

Distal extremities soft tissue sarcomas: Are they so different from other limb localizations?

BACKGROUND AND OBJECTIVES: Soft tissue sarcoma localization in distal extremities (DESTS) of the limbs (hand/fingers, and foot/toes) is unusual. The literature is scarce about their behavior and this study was designed to assess their epidemiological characteristics, outcomes, and prognosis compared to other limb localizations (OLSTS). METHODS: From 1980 to 2010, adult DESTS and OLSTS in 22 centers were included. Demographics, tumor type, treatment modalities, and latest follow-up status were collected. Primary endpoints were overall survival and local/metastatic recurrence incidences. RESULTS: Two hundred five DESTS and 3001 OLSTS were included. The patients were younger, with more female and smaller tumors in DESTS. There were more clear cell/epithelioid sarcomas, synovial sarcomas, and myxoid liposarcomas vs more dedifferentiated liposarcomas in OLSTS. DESTS tumors were less irradiated and more often amputated (24.3% vs 3.4%). The five-year survival rate was 78.2% compared to 68.6% in OLSTS and after multivariate analysis, STS localization did not impact survival or local/metastatic recurrence. CONCLUSION: Though rare and smaller than other limb localizations, DESTS are to be considered as aggressive. Despite a higher amputation rate, the prognosis remains the same as in OLSTS. Limb sparing vs amputation should be carefully assessed in DESTS, especially if grade 3 or of a poor prognosis histological subtype.

Free antero-lateral thigh flap for total knee prosthesis coverage after infection complicating malignant tumour resection.

BACKGROUND: Infection is a common complication of major lower limb-sparing surgery with massive total knee prosthesis (MTKP) reconstruction after extensive tumour resection. When free tissue transfer is required to cover the prosthesis, musculo-cutaneous flaps are usually preferred based on proven efficacy when used in both one-stage and two-stage procedures. The use of a free fascio-cutaneous antero-lateral thigh (FC-ALT) flap in 3 patients with infected knee reconstructions is reported here. MATERIAL AND METHOD: A retrospective study was performed of 3 patients in whom a free FC-ALT flap was used during a two-stage procedure to treat MTKP infection after femoral sarcoma resection. RESULTS: Free FC-ALT flap transfer and exchange arthroplasty were successful in all 3 patients. Two years after the procedure, no patient had required amputation or experienced recurrent infection. CONCLUSION: A free FC-ALT flap can provide adequate coverage of infected MTKP and deserves to be viewed as a valid alternative to free muscle flaps.

Gastrocnemius Myocutaneous Flaps for Knee Joint Coverage.

INTRODUCTION: The gastrocnemius muscular flap has already proven its efficiency for soft tissue coverage in cases of knee joint exposure. However, it may be too small to cover large defects and has not the same aesthetic and mechanical properties as normal skin. Perforator fasciocutaneous flaps have recently been described in knee joint coverage with good results as they replace skin by skin, but they can be hard to harvest. Gastrocnemius flaps can be easily harvested with a planned skin paddle designed over the chosen muscle. This simple technique combines the advantages of muscular and fasciocutaneous flaps for knee joint area coverage. Perforator fasciocutaneous flap take a growing place in coverage of this localization in recent literature, but very few articles report the results of gastrocnemius myocutaneous flaps (MCFs). METHODS: All patients who underwent knee joint coverage with the use of a lateral or medial gastrocnemius MCFs between January 2012 and February 2017 in our university institution were included in this retrospective study. RESULTS: Sixteen gastrocnemius MCFs (10 medial and 6 lateral) were performed. The indication was posttraumatic in 5 cases, posttumoral in 5 cases, and after total knee prosthesis exposure in 6 cases. Skin paddles up to 15 cm in width and 18 cm in length were harvested. Complete healing was achieved in 15 days in all cases without suffering or nonunion. Three flaps were secondarily raised to allow total knee prosthesis reimplantation or arthrodesis, and 4 patients were treated with postoperative radiotherapy without complication. CONCLUSIONS: In addition to its reliability and very easy harvesting, the gastrocnemius MCF allows a robust joint coverage and good skin resurfacing that makes eventual revision easier and allows early radiotherapy. Furthermore, skin paddle also increases the effective area of the flap. This technique should always be considered with the other classic alternatives.

Growth Factors Levels Determine Efficacy of Platelets Rich Plasma Injection in Knee Osteoarthritis: A Randomized Double Blind Noninferiority Trial Compared With Viscosupplementation.

PURPOSE: To assess the noninferiority of a single platelet-rich plasma (PRP) injection compared with hyaluronic acid (HA), to alleviate pain and enhance functional capacity in knee osteoarthritis, and identify biological characteristics of PRP that may affect their efficacy. METHODS: Fifty-four patients with symptomatic knee osteoarthritis received a single injection of either PRP (26 patients) or HA (28 patients). They were assessed at baseline and at 1, 3, and 6 months. The primary endpoint was the change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) score at 3 months, and secondary endpoints were responders' rate (improvement of at least 5 points or 40% of WOMAC total score at 3 months) of pain evaluation and patient's subjective satisfaction. Cell counts and the contents of vascular endothelial growth factor (VEGF), platelet-derived growth factor-AB (PDGF-AB), transforming growth factor beta 1 (TGF-ß1) content of injected PRP were assessed to analyze their relationship with clinical outcome. RESULTS: Both treatments proved their improvement in knee functional status and symptom relief, with a significant decrease observed at 1 month on all scores except for pain VAS in PRP group and WOMAC function score in the HA group. No difference between groups regarding WOMAC and VAS scores was observed. A higher percentage of responders was observed in the PRP group (72.7%) than in the HA group (45.8%) without significance (P = .064). The quantity of injected PDGF-AB and TGF-ß1 correlated with the change in WOMAC scores at 3 months and was lower in responders than in nonresponders (P = .009 and P = .003, respectively). CONCLUSIONS: Current results indicated that a single injection of very pure PRP offers a significant clinical improvement in the management of knee osteoarthritis, equivalent to a single HA injection in this patient population. Moreover, a significant correlation between the doses of TGF-ß1 and PDGF-AB and the worsening of WOMAC score 3 months after the procedure was found. LEVEL OF EVIDENCE: Level II, randomized double blind controlled trial.

Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and ß1-integrin in conventional osteosarcoma.

INTRODUCTION: Currently, very few studies are available concerning the mammalian Hippo pathway in bone sarcomas. YAP/TAZ transcription co-activators are key downstream effectors of this pathway and may also have oncogenic properties. Additionally, recent in-vitro experiments showed that expression of ß1-integrin promoted metastasis in osteosarcomas. This study investigated the expression of YAP/TAZ and ß1-integrin in human osteosarcomas. MATERIALS AND METHODS: We performed automated immunohistochemistry on tissue-microarrays (TMA) in which 69 conventional osteosarcomas biopsies performed prior to chemotherapy were embedded. Cellular localization and semi-quantitative analysis of each immunostain was performed using Immunoreactive Score (IRS) and correlated to clinico-pathological data. RESULTS: Cytoplasmic expression of ß1-integrin was noted in 54/59 osteosarcomas (92%), with 33/59 cases (56%) displaying membranous staining. YAP/TAZ was expressed in 27/45 osteosarcomas (60%), with 14 cases (31%) showing cytoplasmic expression while 13 other cases (28%) displayed nuclear expression. No link was found between YAP/TAZ or ß1-integrin expression and response to chemotherapy. In univariate analysis, YAP/TAZ immunoreactive score was pejoratively correlated with overall survival (p = 0.01). Expression of ß1-integrin on cell membrane was also pejorative for OS (p = 0.045). In multivariate analysis, YAP/TAZ nuclear expression was an independent prognostic factor for PFS (p = 0.035). CONCLUSION: this study indicates that ß1-integrin and YAP/TAZ proteins are linked to prognosis and therefore could be therapeutic targets in conventional osteosarcomas.

Adjuvant treatment with zoledronic acid after extensive curettage for giant cell tumours of bone.

BACKGROUND: Giant cell tumours (GCT) of bone are benign neoplasms associated with a high rate of local recurrence after extensive intra-lesional curettage. Recently, understanding of the biological molecular availability of strong anti-osteoclastic drugs has suggested their potential value in reducing local recurrences after curettage. Through a phase II clinical trial, we investigated the effect of a short treatment with zoledronic acid (ZOL) after intra-lesional curettage of GCT, as well as local recurrence and tolerance of the treatment. METHODS AND PATIENTS: Twenty-four patients were enrolled in a multicentre, phase 2 study. The patients were treated with extensive intra-lesional curettage followed by five courses of ZOL (4 mg IV every 3 weeks). The clinical and biological tolerance of each patient was assessed. Patients were reviewed clinically and by X-ray every 6 months until the end of the study (36 months). RESULTS: Eighteen out of 20 patients reported side-effects with ZOL, mainly grade 1 and 2 effects. The local recurrence rate was 15%; three patients had a recurrence, one at 4 months (huge GCT of the sacrum), one at 24 months (patient who discontinued the treatment after the first course of ZOL), and one after the observational period, at 58 months. Finally, local relapse-free survival was 82 ± 9% at 60 months. CONCLUSION: Short adjuvant treatments with ZOL after extensive intra-lesional curettage of GCT were associated with a low rate of recurrence but did not prevent local recurrence in this study. No serious general adverse effects were observed. More studies are needed to evaluate the potential benefit of medical bisphosphonate injections combined with intra-lesional curettage in the treatment of GCTB.

[Surgery in «around the knee¼ bone tumors]. / Stratégie chirurgicale dans les tumeurs osseuses « du genou ¼

Distal femur and proximal tibia are the main localization of primary malignant bone tumor. Osteosarcoma and Ewing sarcoma are the most frequent. New techniques in imaging, recent development in chemotherapy protocols and surgery sharpening led to major improvement in their management, which allowed to minimize amputation ratio. The complexity of their treatment and their rarity imply the involvement of multidisciplinary approach, in terms of both surgical and medical points of view. After resection, total knee arthroplasty has become the gold standard of reconstruction in such localizations. It uses press fit against healthy bone, thanks to long centromedullar stems, because of major soft tissues resection due to carcinologic surgery rules. The incision is usually antero-medial and the main difficulty is mostly linked to the care of vascular and nervous systems and the extensor apparatus. The conservation (or not) of the latter modifies the surgical technique. Articular invasion will impose to perform a one-piece-articular resection, which will complicate the conservation of the extensor apparatus. There are lots of different techniques and prosthesis. Arthrodesis indications are seldom because prosthesis reconstructions have made proof of their efficacy and their longevity. Functional and oncologic results of this excision and reconstructive surgery are now clearly established. However, this represents complex and risky interventions which will often lead to secondary surgical revision because of the young age of patients and their functional demands. This can only stress the necessity of addressing patients to specialized, network-organized sarcoma teams.

Complete pathological response after sequential therapy with sunitinib and radiotherapy for metastatic clear cell renal carcinoma.

Despite great improvements in the management of metastatic clear cell renal carcinoma, complete responses with antiangiogenic therapies are infrequent and complete pathological responses remain anecdotal. We report the complete pathological response of a solitary bone metastasis from a clear cell renal carcinoma after sequential treatment with sunitinib and radiotherapy. In February 2009, a female patient was diagnosed with clear cell renal carcinoma of the left kidney, bearing only one metastatic site localized in the proximal extremity of the left tibia. Radical nephrectomy was performed at first. Thereafter, sunitinib was administered at standard dose level for four weeks followed by two weeks free at each cycle. The patient underwent palliative radiotherapy between the fifth and the sixth cycle. Due to stable status, a radical surgery of the left knee was then performed and pathological analysis concluded a complete response. This case highlights potential synergy between sunitinib and radiation therapy in clear cell renal carcinoma.