Search

Abstract The aim of this study was to evaluate whether (preoperative) plasma levels of fibrinogen, an essential clotting and acute phase protein, are associated with the prognosis of patients with a liposarcoma, a subtype of sarcoma derived from adipose tissue. We performed a retrospective cohort study of 158 patients with liposarcoma treated at the Department of Orthopaedics of the Medical University of Vienna in Austria from May 1994 to October 2021. Kaplan–Meier curves as well as uni- and multivariable Cox proportional hazard models were performed to evaluate the association between fibrinogen levels and overall survival. Elevated fibrinogen was associated with adverse overall survival in cause specific hazards analysis of mortality (hazard ratio [HR] per 10 mg/dL increase: 1.04; 95% CI 1.02–1.06; p

BackgroundThere is scant evidence to guide decision-making for patients considering total femoral replacement (TFR). We aimed to identify the indication, patient, disease, and surgical technique-related factors associated with failure. We hypothesized that failure occurs more frequently in the setting of revision surgical procedures, with infection as the predominant failure mode.MethodsWe performed a retrospective cohort study of patients receiving total femoral endoprostheses for oncological and revision arthroplasty indications; 166 patients met these criteria. Our primary independent variable of interest was TFR for a revision indication (arthroplasty or limb salvage); the primary outcome was failure. Analyses were performed for patient variables (age, sex, diagnosis group, indication), implant variables (model, decade, length, materials), and treatment variables. We analyzed TFR failures with respect to patient factors, operative technique, and time to failure. We conducted bivariate logistic regressions predicting failure and used a multivariate model containing variables showing bivariate associations with failure.ResultsForty-four patients (27%) had treatment failure. Failure occurred in 24 (23%) of 105 primary TFRs and in 20 (33%) of 61 revision TFRs; the difference was not significant (p = 0.134) in bivariate analysis but was significant (p = 0.044) in multivariate analysis. The mean age at the time of TFR was 37 years in the primary group and 51 years in the revision group (p = 0.0006). Of the patients who had mechanical failure, none had reoccurrence of their original failure mode, whereas all 8 patients from the nonmechanical cohort had reoccurrence of the original failure mode; this difference was significant (p = 0.0001).ConclusionsTFR has a high failure rate and a propensity for deep infection, especially in the setting of revision indications and prior infection. All failed TFRs performed for revision indications for infection or local recurrence failed by reoccurrence of the original failure mode and resulted in amputation.Level of evidenceTherapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Abstract KRAS is mutated in approximately 25% of cancer patients and first KRAS G12C-specific inhibitors showed promising responses. Pancreatic cancer has the highest frequency of KRAS mutations but the prevailing KRAS G12D mutation is difficult to target. Inhibition of the GTP exchange factor (GEF) SOS1—KRAS interaction impairs oncogenic signaling independently of the specific KRAS mutations. In general, cell lines exhibiting KRAS mutations show specific alterations in respect to glucose utilization, signal transduction and stress survival. The aim of this investigation was to check the putative synergy of the SOS1 inhibitor BAY-293 with modulators targeting specific vulnerabilities of KRAS-mutated cell lines in vitro. The cytotoxicity of BAY-293 combinations was tested against MIA PaCa-2 (G12C), AsPC1 (G12D) and BxPC3 (KRAS wildtype) cell lines using MTT tests and calculation of the combination indices (CI) according to the Chou-Talalay method. The results show that BAY-293 synergizes with modulators of glucose utilization, inhibitors of the downstream MAPK pathway and several chemotherapeutics in dependence of the specific KRAS status of the cell lines. In particular, divergent responses for BAY-293 combinations between pancreatic and NSCLC cell lines were observed for linsitinib, superior inhibitory effects of trametinib and PD98059 in NSCLC, and lack of activity with doxorubicin in case of the pancreatic cell lines. Phosphoproteome analysis revealed inhibition of distinct signaling pathways by BAY-293 for MIA PaCa-2 on the one hand and for Aspc1 and BH1362 on the other hand. In conclusion, BAY-293 exhibits synergy with drugs in dependence of the tumor type and specific KRAS mutation.

Abstract Objective To present a case series of spontaneous structural failure of bridging stentgrafts (BSGs) after branched endovascular aortic repair (bEVAR), as well as their failure types and their detection. While bEVAR is a safe and effective procedure, one main limitation is the reintervention rate associated with the BSGs. Structural failure of BSGs, defined as fabric disruption, stent fracture with leak or complete separation is a major cause for reinterventions and difficult to detect in computed tomography angiography (CTA). Methods From a multicenter bEVAR complication database, structural BSG failures were identified. Patient and BSG characteristics, detection mode, failure type, treatment and outcome were recorded and compared with bEVAR patients with intact BSGs. Results Twenty-three BSG failures were detected in 12 patients with only 43% directly identified in CTA, after a mean of 21.4 months after implantation. The BSGs were Advanta (n = 4), E-Ventus (n = 16) and BeGraft (n = 3) in 10 renal, 9 superior mesenteric, and 4 celiac branches. Religning with another BSG was successful in 20/22 cases, one BSG failure necessitated renal branch embolization (organ loss), and one mesenteric bypass surgery. Two reintervention-related mortalities occurred. Conclusion Structural failure of BSGs is a serious limitation for bEVAR, which can result in high reintervention rates and serious complications. BSG failure typically occurs in single-layer types and events are clustered in patients. The necessary reinterventions carry serious morbidity and mortality. Since the use as BSG in bEVAR is off-label with all current BSG manufacturers, caution is advised regarding patient-informed consent.

Bridging stentgrafts (BSGs) are one of the primary limiting factors regarding long-term results after fenestrated endovascular aortic repair (fEVAR). This study aims to report for the first time the outcome of a novel BSG called iCover from a national, multicentric retrospective database. A cohort of 58 patients received 212 BSGs for the renovisceral arteries in fEVAR. Patients were followed-up clinically and with computed-tomography angiography. Study end points were mortality, occurrence of complications, technical success of the BSG implantation, defined as successful deployment with vessel patency and absence of type 1c, 3b, and 3c endoleak, and stability over the follow-up. Three BSG unrelated mortalities (5.1 %), four BSG unrelated major complications (6.8 %) and five minor complications (8.6 %) occurred. The technical success of iCover was 207/212 (97.6 %), target vessel patency was 100 % over a follow-up of 4.0 months, and no late BSG related endoleak was detected. In two cases, the BSG was dislodged from the balloon and could be parked in a safe position without further sequelae (0.9 %). The iCover represents a feasible BSG for fEVAR with an excellent safety profile and technical success rate in the early phase. Prudent post-dilatation and monitoring of the proximal and distal stent ends can potentially further improve outcome. Longer follow-up series are necessary. [ABSTRACT FROM AUTHOR]

Abstract Core needle biopsy (CNB) is gaining in importance due to its advantages in the matter of patient morbidity, time and cost. Nevertheless, controversies still exist regarding the biopsy technique of choice for the accurate diagnosis of soft tissue sarcoma (STS). This retrospective cohort study compared the diagnostic performance between ultrasound-guided CNB and incisional biopsy (IB), both performed by orthopedic surgeons. The aims of the study were to answer the following questions: (1) Is ultrasound-guided CNB a highly reliable modality for diagnosing STSs? (2) Is CNB equally useful to IB for identifying histologic subtype? (3) Had patients who underwent CNB a reduced risk of complications? One-hundred and fifty-three patients who underwent resection of soft tissue sarcoma were classified into two groups according to biopsy technique prior to surgery; CNB group (n = 95) and IB group (n = 58). The final surgical specimens were in 40 patients liposarcoma (myxoid, pleomorphic and dedifferentiated), 39 undifferentiated pleomorphic sarcoma (UPS), 33 myxofibrosarcoma, 10 synovial sarcoma, 10 leiomyosarcoma and in the remaining 21 patients different soft tissue sarcoma entities. Sarcoma location of 71 patients was in the thigh, 19 in the lower leg, 22 in the upper arm and shoulder area; 10 in the knee and gluteal region, 9 in the thoracic region, the residual 12 in other body areas. Malignancy was correctly diagnosed in 87% (83 of 95) for the CNB group and 93% (54/58) for the IB group. Correct identification rate of histologic subtype was 80% (76 of 95) in the CNB group and 83% (48 of 58) in the IB group. There were no significant differences in the correct diagnosis rates of malignancy and subtype between the two techniques. No complications were seen in the CNB group, whereas 2 patients in whom IB was performed developed pulmonary embolism and 1 patient surgical site infection. Ultrasound-guided CNB is highly accurate and not inferior to IB in diagnosing the dignity of lesions and histologic subtype in patients with suspected STSs.

Abstract Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate. Questions/purpose This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. Methods This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF. Results Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3–85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group. Conclusion Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.

KRAS is mutated in approximately 25% of Non-small Cell Lung Cancer (NSCLC) patients and first specific inhibitors showed promising responses that may be improved by concurrent interference with downstream signaling pathways. Cell lines exhibiting KRAS mutations show specific sensitivities to modulators affecting glucose utilization, signal transduction and cell survival. Novel SOS1-directed inhibitors with a broader anticancer coverage such as BAY-293 and BI-3406 inhibit KRAS through the hindrance of SOS1-KRAS interactions. The aim of this study was to check the putative synergy of BAY-293 with modulators having revealed specific vulnerabilities of KRAS-mutated cell lines. The present investigation tested the cytotoxicity of BAY-293 combinations against a series of Osimertinib-resistant primary NSCLC cell lines using MTT tests and calculation of combination indices according to the Chou-Talalay method. The results show that BAY-293 synergizes with modulators of glucose metabolism, inhibitors of cellular proliferation, several chemotherapeutics and a range of diverse modulators, thus corroborating the chemosensitivities of cells expressing mutated KRAS. In conclusion, BAY-293 exerts cytotoxicity with a wide range of drugs against Osimertinib-resistant primary NSCLC cell lines. The administration of pan-KRAS inhibitors alone may be limited in vivo by toxicity to normal tissues but made feasible by its use as part of suitable drug combinations. This study shows that BAY-293 combinations are active against NSCLC cells not further amenable to mutated EGFR-directed targeted therapy and results likewise hold relevance for pancreatic and colon cancer.

Abstract Background Self-expanding nitinol stents must be oversized at least by a minimal amount to ensure contact with the vessel wall and prevent migration. Once the stent is deployed it exerts a continuous force upon the vascular wall, termed chronic outward force (COF). Animal studies have found an increased neointimal hyperplasia in stents with high oversizing and thus high COF. Data about correlation between COF and neointimal hyperplasia in humans are currently lacking. The objective of the BIOFLEX-COF trial is to prospectively investigate differences in formation of intimal hyperplasia at 1 and 2 years after implantation of nitinol stents with high versus low COF in de novo femoropopliteal occlusive arterial lesions. Methods The BIOFLEX-COF trial is a prospective, quantitative, randomized study. Eighty subjects with symptomatic peripheral arterial lesions eligible for endovascular stent implantation will be enrolled and randomly assigned to either a high COF group (LifeStent Flexstar, Bard Peripheral Vascular Inc., Tempe, AZ, USA) or low COF group (Pulsar, Biotronik AG, Bülach, Switzerland) using an online randomization program to generate a random 1:1 group allocation (block randomization). After implantation and dilatation, COF at every 2 mm along the stent axis will be calculated from the actual stent diameter versus its nominal diameter. There will be two follow-up evaluations at 12 and 24 months. Primary endpoint is the amount of in-stent neointima at 1 year, assessed by contrast-enhanced CT angiography (CTA). In the control examinations, stent diameter and true lumen diameter will be measured on DICOM images every 2 mm along the stent axis to quantify the relative amount of in-stent restenosis. Secondary objectives are the amount of in-stent neointima at 2 years, device- and procedure-related adverse events and target lesion revascularization (TLR) rate. The scheduled time for recruitment is 2 years. Recruitment is expected to be complete in October 2017. Discussion This trial is the first to prospectively investigate the influence of COF on stent patency. If successful, the results will aid in a more precise selection of stent type and size in a given target vessel. The present study is challenging in that it compares two different self-expanding nitinol stents head-to-head against each other. To optimize the power of this study, traditional binary outcome parameters such as TLR and restenosis at Doppler ultrasound were dropped as primary endpoints. Instead, the amount of neointima inside the stent accessed by CTA was selected as (continuous) outcome parameter. Trial registration ClinicalTrials.gov Identifier: NCT03097679 . Date of registration: 14 March 2017 (retrospectively registered).

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the 22nd week of gestation.

PURPOSE:The incidence of recurrent infections in patients following one or two stage revision for infected megaprostheses after resection of bone tumours was investigated. The difference between retaining at least one well fixed stem and a complete removal of the megaprosthesis during a two stage revision was also analysed. METHODS:627 patients who experienced a replacement of a musculoskeletal tumour by megaprostheses were recorded. An infection occurred in 83 of 621 patients available for follow-up. 61 patients underwent one stage revision, and 16 patients two stage revision for the first revision surgery. In the entire study period, two stage revision was performed 32 times (first, second, and third revision). RESULTS:The cumulative incidence analysis showed a reinfection probability after one stage revision of 18% at one year, 30% at two years, 39% at five years, 46% at ten years, and 56% at 15 years. After two stage revision, a reinfection probability of 28% at two years, and 48% at five years was calculated. Cumulative incidence curves did not differ significantly (Gray's test; p = 0.51) between one and two stage revision (with and without complete removal of the stems). In two stage revision (n = 32), a statistically significant difference in infection rates between patients treated with complete removal of the megaprosthesis (n = 18) including anchorage stems and patients with at least one retained stem (n = 14) was shown (Fisher's exact test, p = 0.029). CONCLUSION:Two stage revisions with complete removal of the megaprosthesis showed the best results among limb salvage procedures for the treatment of infected megaprosthesis.

BACKGROUND AND OBJECTIVES:Treatment of pelvic tumors remains challenging due to complex anatomy, poor oncological outcome and high complication rates. We sought to investigate the long-term oncological and surgical outcome of these patients. METHODS:Between 1980 and 2012, 147 patients underwent surgical treatment for pelvic sarcoma. Histological diagnosis was Chondrosarcoma in 54, Ewing's Sarcoma/PNET in 37, Osterosarcoma in 32 and others in 24 patients. Statistical analysis for the evaluation of oncological and surgical outcome was performed by applying Cox proportional hazards regression and Fine-Gray regression models for competing risk (CR) endpoints. RESULTS:The estimated overall survival (OS) to death was 80%, 45% and 37% at 1, 5 and 10 years, respectively. Univariate analyses revealed a statistically significant unadjusted influence of age age (p = 0.038; HR = 1.01), margin (p = 0.043; HR = 0.51) and grade (p = 0.001; HR = 2.27) on OS. Considering the multivariable model, grade (p = 0.005; HR = 3.04) and tumor volume (p = 0.014; HR = 1.18) presented themselves as independent prognostic factors on OS. CR analysis showed a cumulative incidence for major complication of 31% at 5 years. Endoprosthetic reconstruction had a higher risk for experiencing a major complication (p

The proximal tibia (pT) is a common site for bone tumors. Improvements in imaging, chemotherapy and surgical technique made limb salvage surgery the treatment of choice. Yet, reconstructions of the pT have been associated with less favorable outcome compared to other parts of the extremities. The aim of this study was to evaluate the outcome of patients with a modular endoprosthetic reconstruction of the pT.Eighty-one consecutive patients with an average age of 29 years underwent endoprosthetic reconstruction of the pT. Postoperative complications were categorized according to the ISOLS classification, and revision-free survival until first complication (any Type 1-5), soft tissue failure (Type 1), aseptic loosening (Type 2), structural failure (Type 3), infection (Type 4), and local tumor progression (Type 5) was estimated by using a Fine-Gray model for competing risk analyses for univariate and multivariable regression with Firth's bias correction.A total of 45 patients (56%) had at least one complication. Cumulative incidence for complication Types 1 to 5 at 5 years with death and amputation as competing events revealed a risk of 41% for the first complication, 14% for Type 1, 16% for Type 2, 11% for Type 3, 17% for Type 4, and 1% for Type 5.Despite inclusion of amputation and death as strong competing events, pT replacements are still associated with a high risk of postoperative failures. The results suggest that infection and soft tissue failures (Type 1 and 5) seem to depend from each other. Sufficient soft tissue reconstruction and closure allow better function and reduce the risk of infection as the most prominent complication. The use of a rotating hinge design has significantly reduced structural failures over time.