Long-term clinical and radiological outcome of a cementless titanium-coated total knee arthroplasty system.

INTRODUCTION: To ensure a high-quality standard, it is important to frequently evaluate different prostheses models to avoid prostheses with high failure rates. Thus, the aim of the study was to evaluate the long-term outcome of the uncemented titanium-coated total knee arthroplasty (TKA) system (Advanced Coated System (ACS) III, Implantcast, GERMANY). We hypothesized that the ACS III would have a similar performance as other cemented TKA systems. MATERIALS AND METHODS: A total of 540 ACS III mobile-bearing knee joint prostheses were implanted in 495 patients. The visual analogue scale (VAS) score, Tegner activity score (TAS), knee society score (KSS), Western Ontario and McMaster (WOMAC) score, and the Short Form 12 (SF-12) score for the evaluation of quality of life (QoL) were taken after at least 9 years of follow-up. In addition, we measured range of motion (ROM) and assessed potential sex differences. In addition, the survival analysis was calculated at a median follow-up of 16.7 years. RESULTS: At the final follow-up, 142 patients had died, and 38 had been lost to follow-up. The rate of revision-free implant survival at 16.7 years was 90.0% (95% CI 87.1-92.2%) and the rate of infection-free survival was 97.0% (IQR 95.2-98.2%). The reasons for revision surgery were aseptic loosening (32.9%), followed by infection (27.1%), inlay exchange (15.9%), and periprosthetic fractures (5.7%). At the clinical follow-up visit, the mean VAS score was 1.9 ± 1.9, the median TAS was 3 (IQR 2-4), and the mean KSS for pain and function were 83.5 ± 15.3 and 67.5 ± 25.2, respectively. The mean WOMAC score was 81.1 ± 14.9, and the median SF-12 scores for physical and mental health were 36.9 (IQR 29.8-45.1) and 55.8 (IQR 46.2-61.0), respectively. The mean knee flexion was 102.0° ± 15.4°. Male patients had better clinical outcome scores than female patients [SF-12 mental health score, p = 0.037; SF-12 physical health score, p = 0.032; KSS pain score (p < 0.001), and KSS functional score (p < 0.001)]. CONCLUSION: The ACS III TKA system is a suitable option for the treatment of end-stage osteoarthritis of the knee joint because of its adequate long-term survival. Our findings are in line with published data on similar TKA systems that have shown favourable clinical scores in males. LEVEL OF EVIDENCE: Level III-Retrospective cohort study.

Spatial tumour gene signature discriminates neoplastic from non-neoplastic compartments in colon cancer: unravelling predictive biomarkers for relapse.

BACKGROUND: Opting for or against the administration of adjuvant chemotherapy in therapeutic management of stage II colon cancer remains challenging. Several studies report few survival benefits for patients treated with adjuvant therapy and additionally revealing potential side effects of overtreatment, including unnecessary exposure to chemotherapy-induced toxicities and reduced quality of life. Predictive biomarkers are urgently needed. We, therefore, hypothesise that the spatial tissue composition of relapsed and non-relapsed colon cancer stage II patients reveals relevant biomarkers. METHODS: The spatial tissue composition of stage II colon cancer patients was examined by a novel spatial transcriptomics technology with sub-cellular resolution, namely in situ sequencing. A panel of 176 genes investigating specific cancer-associated processes such as apoptosis, proliferation, angiogenesis, stemness, oxidative stress, hypoxia, invasion and components of the tumour microenvironment was designed to examine differentially expressed genes in tissue of relapsed versus non-relapsed patients. Therefore, FFPE slides of 10 colon cancer stage II patients either classified as relapsed (5 patients) or non-relapsed (5 patients) were in situ sequenced and computationally analysed. RESULTS: We identified a tumour gene signature that enables the subclassification of tissue into neoplastic and non-neoplastic compartments based on spatial expression patterns obtained through in situ sequencing. We developed a computational tool called Genes-To-Count (GTC), which automates the quantification of in situ signals, accurately mapping their position onto the spatial tissue map and automatically identifies neoplastic and non-neoplastic tissue compartments. The GTC tool was used to quantify gene expression of biological processes upregulated within the neoplastic tissue in comparison to non-neoplastic tissue and within relapsed versus non-relapsed stage II colon patients. Three differentially expressed genes (FGFR2, MMP11 and OTOP2) in the neoplastic tissue compartments of relapsed patients in comparison to non-relapsed patients were identified predicting recurrence in stage II colon cancer. CONCLUSIONS: In depth spatial in situ sequencing showed potential to provide a deeper understanding of the underlying mechanisms involved in the recurrence of disease and revealed novel potential predictive biomarkers for disease relapse in colon cancer stage II patients. Our open-access GTC-tool allowed us to accurately capture the tumour compartment and quantify spatial gene expression in colon cancer tissue.

What Is the Risk of Dislocation and Revision in Proximal Femoral Replacement with Dual-mobility Articulation After Two-stage Revision for Periprosthetic Hip Infection?

BACKGROUND: Dislocation is a major complication of revision THA after two-stage exchange for periprosthetic joint infection (PJI). The likelihood of dislocation can be particularly high if megaprosthetic proximal femoral replacement (PFR) has been performed during a second-stage reimplantation. Dual-mobility acetabular components are an established way of reducing the instability risk in revision THA; however, the likelihood of dislocation for dual-mobility reconstructions in the setting of a two-stage PFR has not been studied systematically, although patients with these reconstructions might be at an increased risk. QUESTIONS/PURPOSES: (1) What is the risk of dislocation and revision for dislocation in patients who underwent PFR with a dual-mobility acetabular component as part of two-stage exchange for hip PJI? (2) What is the risk of all-cause implant revision and what other procedures were performed (apart from revision for a dislocation) in these patients? (3) What potential patient-related and procedure-related factors are associated with dislocation? METHODS: This was a retrospective study from a single academic center including procedures performed between 2010 and 2017. During the study period, 220 patients underwent two-stage revision for chronic hip PJI. Two-stage revision was the approach of choice for chronic infections, and we did not perform single-stage revisions for this indication during the study period. Thirty-three percent (73 of 220) of patients underwent second-stage reconstruction with a single-design, modular, megaprosthetic PFR because of femoral bone loss, using a cemented stem. A cemented dual-mobility cup was the approach of choice for acetabular reconstruction in the presence of a PFR; however, 4% (three of 73) were reconstructed with a bipolar hemiarthroplasty to salvage an infected saddle prosthesis, leaving 70 patients with a dual-mobility acetabular component and a PFR (84% [59 of 70]) or total femoral replacement (16% [11 of 70]). We used two similar designs of an unconstrained cemented dual-mobility cup during the study period. The median (interquartile range) patient age was 73 years (63 to 79 years), and 60% (42 of 70) of patients were women. The mean follow-up period was 50 ± 25 months with a minimum follow-up of 24 months for patients who did not undergo revision surgery or died (during the study period, 10% [seven of 70] died before 2 years). We recorded patient-related and surgery-related details from the electronic patient records and investigated all revision procedures performed until December 2021. Patients who underwent closed reduction for dislocation were included. Radiographic measurements of cup positioning were performed using supine AP radiographs obtained within the first 2 weeks after surgery using an established digital method. We calculated the risk for revision and dislocation using a competing-risk analysis with death as a competing event, providing 95% confidence intervals. Differences in dislocation and revision risks were assessed with Fine and Gray models providing subhazard ratios. All p values were two sided and the p value for significance was set at 0.05. RESULTS: The risk of dislocation (using a competing-risks survivorship estimator) was 17% (95% CI 9% to 32%) at 5 years, and the risk of revision for dislocation was 12% (95% CI 5% to 24%) at 5 years among patients treated with dual-mobility acetabular components as part of a two-stage revision for PJI of the hip. The risk of all-cause implant revision (using a competing-risk estimator, except for dislocation) was 20% (95% CI 12% to 33%) after 5 years. Twenty-three percent (16 of 70) of patients underwent revision surgery for reinfection and 3% (two of 70) of patients underwent stem exchange for a traumatic periprosthetic fracture. No patients underwent revision for aseptic loosening. We found no differences in patient-related and procedure-related factors or acetabular component positioning for patients with dislocation with the numbers available; however, patients with total femoral replacements had a higher likelihood of dislocation (subhazard ratio 3.9 [95% CI 1.1 to 13.3]; p = 0.03) and revision for a dislocation (subhazard ratio 4.4 [95% CI 1 to 18.5]; p = 0.04) than those who received PFR. CONCLUSION: Although dual-mobility bearings might be an intuitive potential choice to reduce the dislocation risk in revision THA, there is a considerable dislocation risk for PFR after two-stage surgery for PJI, particularly in patients with total femoral replacements. Although the use of an additional constraint might appear tempting, published results vary tremendously, and future studies should compare the performance of tripolar constrained implants to that of unconstrained dual-mobility cups in patients with PFR to reduce the risk of instability. LEVEL OF EVIDENCE: Level III, therapeutic study.

Mechanically aligned total knee arthroplasty with the extension-first technique does not equally restore neutral knee alignment in all preoperative knee phenotypes.

PURPOSE: The aim of this study was to determine the change in the long leg axis according to the preoperative knee phenotype using the mechanically aligned extension-first technique in total knee arthroplasty. The hypothesis of this study was that the knee phenotype would have an impact on the postoperative leg axis. METHODS: This was a retrospective comparative study comprising 224 whole-leg radiographs of 112 patients. The leg axes of the pre- and postoperative radiographs were measured and categorized into three preoperative limb phenotypes (based on the hip-knee-ankle angle [HKA]) according to Hirschmann et al. (varus-HKA < 178.5°, neutral-HKA 178.5°-181.5°, and valgus-HKA > 181.5°). Additionally, femoral phenotypes (based on the femoral mechanical angle [FMA], i.e., the mechanical medial distal femoral angle [mMDFA], as well as the tibial phenotypes [based on the tibial mechanical angle, i.e., the medial proximal tibial angle (MPTA)] was calculated. The change in the long leg axis was analyzed and compared with the preoperative limb phenotype. RESULTS: Significantly more patients with preoperative varus alignment shifted to neutral alignment (46.3%, n = 31) than did patients with preoperative valgus alignment (38.9%; n = 14). Moreover, 43.3% of patients (n = 29) with the varus phenotype remained in a varus alignment, compared with the 58.3% of patients with preoperative valgus phenotype (n = 21) remaining in valgus alignment. These findings were similar for both females (p < 0.001) and males (p = 0.015). CONCLUSION: Using an extension-first mechanically aligned surgical technique, varus phenotypes predominantly result in neutral leg axes or remain varus, neutral phenotypes remain neutral, and valgus phenotypes remain valgus or change to neutral phenotypes. This study showed that preoperative knee phenotypes in valgus knees influence this technique more strongly than estimated in previous investigations, which is in line with modern alignment philosophies for TKA. LEVEL OF EVIDENCE: Level IV, retrospective comparative study.

Artificial intelligence-based computer-aided system for knee osteoarthritis assessment increases experienced orthopaedic surgeons' agreement rate and accuracy.

PURPOSE: The aims of this study were to (1) analyze the impact of an artificial intelligence (AI)-based computer system on the accuracy and agreement rate of board-certified orthopaedic surgeons (= senior readers) to detect X-ray features indicative of knee OA in comparison to unaided assessment and (2) compare the results to those of senior residents (= junior readers). METHODS: One hundred and twenty-four unilateral knee X-rays from the OAI study were analyzed regarding Kellgren-Lawrence grade, joint space narrowing (JSN), sclerosis and osteophyte OARSI grade by computerized methods. Images were rated for these parameters by three senior readers using two modalities: plain X-ray (unaided) and X-ray presented alongside reports from a computer-assisted detection system (aided). After exclusion of nine images with incomplete annotation, intraclass correlations between readers were calculated for both modalities among 115 images, and reader performance was compared to ground truth (OAI consensus). Accuracy, sensitivity and specificity were also calculated and the results were compared to those from a previous study on junior readers. RESULTS: With the aided modality, senior reader agreement rates for KL grade (2.0-fold), sclerosis (1.42-fold), JSN (1.37-fold) and osteophyte OARSI grades (3.33-fold) improved significantly. Reader specificity and accuracy increased significantly for all features when using the aided modality compared to the gold standard. On the other hand, sensitivity only increased for OA diagnosis, whereas it decreased (without statistical significance) for all other features. With aided analysis, senior readers reached similar agreement and accuracy rates as junior readers, with both surpassing AI performance. CONCLUSION: The introduction of AI-based computer-aided assessment systems can increase the agreement rate and overall accuracy for knee OA diagnosis among board-certified orthopaedic surgeons. Thus, use of this software may improve the standard of care for knee OA detection and diagnosis in the future. LEVEL OF EVIDENCE: Level II.

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.

Restoring tibial obliquity for kinematic alignment in total knee arthroplasty: conventional versus patient-specific instrumentation.

INTRODUCTION: In total knee arthroplasty (TKA), tibial obliquity-restoration using kinematic alignment (KA) poses a major difference to conventional mechanical alignment. This study aimed at analysing the accuracy of conventional instrumentation (CI) versus patient-specific instrumentation (PSI) to restore anatomic tibial obliquity measured by the medial proximal tibial angle (MPTA) on conventional X-rays. MATERIALS AND METHODS: One-hundred patients were randomized to receive CI (n = 50) or PSI (n = 50) for TKA. Further 100 patients received CI without randomisation, resulting in 200 patients in total (127 women, mean age: 70.7 (range: 48-90 years). Pre- and postoperative X-rays were measured twice by two observers with a 2-week break in-between. Inter- and intraclass correlations were calculated and postoperative tibial obliquity compared to preoperative anatomy. RESULTS: In 150 patients with CI, no case with tibial obliquity-deviation greater than 2° was found, whilst 21.3% (n = 32) and 0.7% (n = 1) of cases and had a deviation of 0°-1°, and 1°-2°, respectively. In the remaining 78.0% (n = 117), tibial obliquity was restored. In 50 patients with PSI, no single case with a deviation greater than 1° was found. Sixty percent (n = 30) had a deviation of 0°-1°. In the remaining 40.0% (n = 20), no deviation from preoperative measurements was found. Consequently, CI resulted in a significantly smaller change in tibial obliquity from preoperative to postoperative than PSI (p < 0.001). Inter- and intra-class correlations showed a substantial agreement (any ICC > 0.90). CONCLUSION: Both conventional and patient-specific instrumentation revealed adequate results with respect to restoring tibial obliquity in kinematically aligned TKA, with conventional instrumentation achieving superior results.

Patients successfully lose body weight after primary total knee arthroplasty but not more than a matched general population.

INTRODUCTION: High BMI is associated with increased risk for knee osteoarthritis, ultimately necessitating total knee arthroplasty (TKA). The aim of this retrospective study was to (1) analyse the amount of postoperative long-term weight loss as reflected by BMI change in TKA patients, (2) identify factors associated with increased change in BMI, and to (3) compare changes with BMI trends of a general population. MATERIALS AND METHODS: Overall, 298 TKA patients [198 females; mean age: 65.1 ± 7.9 years, median follow-up 8.8 (interquartile range: 5.9-10.8 years)] were included in the final evaluation and compared with an age group-matched control group from the general population regarding weight trends between 2006 and 2014. Main variable of interest in both cohorts was body mass index (BMI). Linear regression analyses were performed to assess changes in weight and BMI over time between TKA patients and the general population. Furthermore, mixed linear-effects models were constructed to analyse the potential change in BMI independent from age and gender. RESULTS: In TKA patients, a significant drop in BMI by 0.8 ± 3.2 points from postoperative to final follow-up was observed (p < 0.001), with reduction being significant independently from age (p = 0.382), gender (p = 0.310), or revision surgery (p = 0.195). In the general population, likewise a significant BMI-decrease by 0.7 ± 6.1 points was observed between 2006 and 2014, with younger people (p = 0.004) and females (p < 0.001) being more likely to reduce BMI. Yet, BMI-decrease between TKA patients and the general population over time was comparable (p = 0.734). Notably, patients with initially higher BMI were significantly more likely to lose weight postoperatively than normal-weight patients (p < 0.001). CONCLUSIONS: Our results point against the notion that TKA patients lose a considerable amount of weight in comparison to the general population as soon as improved joint function and pain relief have been achieved. Thus, individualized patient education programmes should be reinforced, promoting a healthy lifestyle.

Smokers have increased risk of soft-tissue complications following primary elective TKA.

INTRODUCTION: Smoking has been associated with numerous adverse outcomes following surgical procedures. The purpose of this study was to investigate, whether smoking status at time of surgery influences the outcome of primary TKA. MATERIALS AND METHODS: Six hundred and eighty-one patients who underwent primary TKA between 2003 and 2006 were included in the study. Smoking status was defined as current, former, and never smoker. Complications leading to revisions were assessed until 17 years of follow-up. Functional outcome was evaluated using clinical scores: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, Short Form-12 Physical and Mental Component Summaries (SF-12PCS/MCS), and Knee Society Function and Knee Score (KSFS and KSKS). RESULTS: At a mean follow-up of 95 months (± 47 months), 124 complications led to revision surgery. Soft-tissue complications (OR, 2.35 [95% CI 1.08-5.11]; p = 0.032), hematoma formation (OR, 5.37 [95% CI 1.01-28.49]; p = 0.048), and restricted movement (OR, 3.51 [95% CI 1.25-9.84]; p = 0.017) were more likely to occur in current smokers than never smokers. Current smokers were more likely to score higher at KSFS (p < 0.001) and SF-12PCS (p = 0.0197) compared to never smokers. For overall revision, differences were noted. CONCLUSION: Current smoking increases risk of soft-tissue complications and revision after primary TKA, especially due to hematoma and restricted movement. Smoking cessation programs could reduce the risk of revision surgery.

The Immune Deficiency and Dysregulation Activity (IDDA2.1 'Kaleidoscope') Score and Other Clinical Measures in Inborn Errors of Immunity.

Quantifying the phenotypic features of rare diseases such as inborn errors of immunity (IEI) helps clinicians make diagnoses, classify disorders, and objectify the disease severity at its first presentation as well as during therapy and follow-up. Furthermore, it may allow cross-sectional and cohort comparisons and support treatment decisions such as an evaluation for transplantation. On the basis of a literature review, we provide a descriptive comparison of ten selected scores and measures frequently used in IEI and divide these into three categories: (1) diagnostic tools (for Hyper-IgE syndrome, hemophagocytic lymphohistiocytosis, and Wiskott-Aldrich syndrome), (2) morbidity and disease activity measures (for common variable immune deficiency [CVID], profound combined immune deficiency, CTLA-4 haploinsufficiency, immune deficiency and dysregulation activity [IDDA], IPEX organ impairment, and the autoinflammatory disease activity index), and (3) treatment stratification scores (shown for hypogammaglobulinemia). The depth of preclinical and statistical validations varies among the presented tools, and disease-inherent and user-dependent factors complicate their broader application. To support a comparable, standardized evaluation for prospective monitoring of diseases with immune dysregulation, we propose the IDDA2.1 score (comprising 22 parameters on a 2-5-step scale) as a simple yet comprehensive and powerful tool. Originally developed for use in a retrospective study in LRBA deficiency, this new version may be applied to all IEI with immune dysregulation. Reviewing published aggregate cohort data from hundreds of patients, the IDDA kaleidoscope function is presented for 18 exemplary IEI as an instructive phenotype-pattern visualization tool, and an unsupervised, hierarchically clustered heatmap mathematically confirms similarities and differences in their phenotype expression profiles.

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.

Long-term clinical and radiological outcomes following surgical treatment for symptomatic pediatric flexible flat feet: a systematic review.

BACKGROUND AND PURPOSE: Albeit pediatric flexible flat foot (FFF) is a common condition, only a minority of patients become symptomatic. Long-term outcomes of surgically treated pediatric patients with symptomatic FFF are largely unknown. In this systematic review, studies providing outcomes at a mean follow-up of at least 4 years after the procedure in these patients were analyzed. MATERIAL AND METHODS: A PubMed search was undertaken involving original articles published up to July 2021 on outcome in children aged 6 to 14 with surgically treated FFF and mean (or minimum) follow-up of at least 4 years. Radiographic and clinical outcomes were analyzed. RESULTS: Of initially 541 entries, 10 could be included in the systematic review (all level IV), involving 846 pediatric patients with 1,536 symptomatic FFF. Pooled mean radiological (n = 8) and clinical follow-up (n = 10) was 5.3 (range 0.5-15) and 7.0 (range 4.1-15) years, respectively. Surgical procedures included arthroereisis (n = 8), lateral column lengthening (n = 1), and Horseman procedure (n = 1). Overall relative frequency of implant-associated complications and wound-healing problems was 3.2% and 1.3%, as well as 2.8% and 1.6% following subtalar arthroereisis only. From preoperative to latest radiological assessment following subtalar arthroereisis (including 3 studies with radiological follow-up < 48 months), pooled median decrease in talonavicular coverage angle (TNCA; -9.2°), anteroposterior talocalcaneal angle (A-TCA; -6.5°), lateral talocalcaneal angle (L-TCA; -3.5°), talar declination angle (TDA; -14°), Moreau Costa Bertani angle (MCB; -13°), and talo-firstmetatarsal angle (L-T1MA; -10°) was observed, as was an increase in calcaneal pitch (4.5°). INTERPRETATION: In symptomatic pediatric FFF patients, surgery is associated with a manageable complication profile, and results in satisfactory long-term clinical as well as radiological outcome. Yet scientific evidence is low, warranting larger scaled studies in the future.

Pre-operative templating in THA using a short stem system: precision and accuracy of 2D versus 3D planning method.

BACKGROUND: Total hip arthroplasty (THA) is the most successful orthopaedic surgery of the past century. The current study aimed to compare the accuracy of digital planning using 2D versus 3D templating. MATERIALS AND METHODS: Ninety-five THAs in 90 patients were included in the current study. Pre- and post-operative X-rays (in two planes) and low-dose rotation computed tomography scans from hip to foot were performed. Paired t-test and regression analyses were conducted to compare 2D and 3D templating accuracy of the definitive implant. RESULTS: Cup size planned both with 2D (p < 0.0001) and 3D (p = 0.012) templating was significantly different from the definitively used cup size. The difference between the 2D-planned and implanted stem size (p < 0.0001) was statistically significant. In contrast, there were no significant differences in the 3D-planned and implanted stem size (p = 0.181). Three-dimensional templating showed significantly higher accuracy than 2D templating in terms of cup size (1.1 ± 1.4 versus 1.7 ± 1.8; p = 0.007) and stem size (0.3 ± 0.6 versus 0.7 ± 0.7; p < 0.0001). With increasing body mass index (BMI), 2D templating of the stem became more inaccurate (p = 0.041). Remarkably, 3D templating remained accurate for all components (stem, p = 0.533; cup, p = 0.479) despite increasing BMI. CONCLUSION: Despite extended planning time and increased exposure to radiation, 3D-based planning showed higher accuracy than 2D templating, especially in obese patients. On the basis of our results, we believe that 3D-based pre-operative planning in THA is justifiable and beneficial in patients with increased BMI. LEVEL OF EVIDENCE: III.

Extra-abdominal desmoid tumor fibromatosis: a multicenter EMSOS study.

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.

What Is the Implant Survivorship and Functional Outcome After Total Humeral Replacement in Patients with Primary Bone Tumors?

BACKGROUND: Total humeral replacement is an option to reconstruct massive bone defects after resection of locally advanced bone tumors of the humerus. However, implant survivorship, potential risk factors for implant revision surgery, and functional results of total humeral replacement are poorly elucidated because of the rarity of the procedure. QUESTIONS/PURPOSES: We asked: (1) What is the revision-free implant and overall limb survivorship after total humerus replacement? (2) What factors are associated with implant revision surgery? (3) What is the functional outcome of the procedure as determined by the Musculoskeletal Tumor Society (MSTS) score and the American Shoulder and Elbow Surgeons (ASES) score? METHODS: Between August 1999 and December 2018, 666 patients underwent megaprosthetic reconstruction after resection of a primary malignant or locally aggressive/rarely metastasizing tumor of the long bones at our department. In all, 23% (154) of these patients had a primary tumor located in the humerus. During the study, we performed total humeral replacement in all patients with a locally advanced sarcoma, in patients with pathological fractures, in patients with skip metastases, or in patients with previous intralesional contaminating surgery, who would have no sufficient bone stock for a stable implant fixation for a single joint megaprosthetic replacement of the proximal or distal humerus. We performed no biological reconstructions or reconstructions with allograft-prosthetic composites. As a result, 5% (33 of 666) of patients underwent total humerus replacement. Six percent (2 of 33) of patients were excluded because they received a custom-made, three-dimensionally (3-D) printed hemiprosthesis, leaving 5% (31) of the initial 666 patients for inclusion in our retrospective analysis. Of these, 6% (2 of 31) had surgery more than 5 years ago, but they had not been seen in the last 5 years. Median (interquartile range) age at the time of surgery was 15 years (14 to 25 years), and indications for total humeral replacement were primary malignant bone tumors (n = 30) and a recurring, rarely metastasizing bone tumor (n = 1). All megaprosthetic reconstructions were performed with a single modular system. The implanted prostheses were silver-coated beginning in 2006, and beginning in 2010, a reverse proximal humerus component was used when appropriate. We analyzed endoprosthetic complications descriptively and assessed the functional outcome of all surviving patients who did not undergo secondary amputation using the 1993 MSTS score and the ASES score. The median (IQR) follow-up in all survivors was 75 months (50 to 122 months), with a minimum follow-up period of 25 months. We evaluated the following factors for possible association with implant revision surgery: age, BMI, reconstruction length, duration of surgery, extraarticular resection, pathological fracture, previous intralesional surgery, (neo-)adjuvant radio- and chemotherapy, and metastatic disease. RESULTS: The revision-free implant survivorship at 1 year was 77% (95% confidence interval 58% to 89%) and 74% (95% CI 55% to 86%) at 5 years. The overall limb survivorship was 93% (95% CI 75% to 98%) after 1 and after 5 years. We found revision-free survivorship to be lower in patients with extraarticular shoulder resection compared with intraarticular resections (50% [95% CI 21% to 74%] versus 89% [95% CI 64% to 97%]) after 5 years (subhazard ratios for extraarticular resections 4.4 [95% CI 1.2 to 16.5]; p = 0.03). With the number of patients available for our analysis, we could not detect a difference in revision-free survivorship at 5 years between patients who underwent postoperative radiotherapy (40% [95% CI 5% to 75%]) and patients who did not (81% [95% CI 60% to 92%]; p = 0.09). The median (IQR) MSTS score in 9 of 13 surviving patients after a median follow-up of 75 months (51 to 148 months) was 87% (67% to 92%), and the median ASES score was 83 (63 to 89) of 100 points, with higher scores representing better function. CONCLUSION: Total humeral replacement after resection of locally advanced bone tumors appears to be associated with a good functional outcome in patients who do not die of their tumors, which in our study was approximately one- third of those who were treated with a resection and total humerus prosthesis. However, the probability of early prosthetic revision surgery is high, especially in patients undergoing extraarticular resections, who should be counseled accordingly. Still, our results suggest that if the prosthesis survives the first year, further risk for revision appears to be low. Future studies should reexamine the effect of postoperative radiotherapy on implant survival in a larger cohort and evaluate whether the use of soft tissue coverage with plastic reconstructive surgery might decrease the risk of early revisions, especially in patients undergoing extraarticular resections. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Prognostic Significance of Eukaryotic Translation Initiation Factors (eIFs) in Endometrial Cancer.

Whilst the role of eukaryotic translation initiation factors (eIFs) has already been investigated in several human cancers, their role in endometrial cancer (EC) is relatively unknown. In the present retrospective study, 279 patients with EC (1180 samples) were included (mean age: 63.0 years, mean follow-up: 6.1 years). Samples were analysed for expression of 7 eIFs subunits (eIF2α, eIF3c, eIF3h, eIF4e, eIF4g, eIF5, eIF6) through immunohistochemistry and western blotting. Fifteen samples of healthy endometrium served as controls. Density and intensity were assessed and mean combined scores (CS) calculated for each patient. Upon immunohistochemistry, median eIF5 CS were significantly higher in EC as compared with non-neoplastic tissue (NNT, p < 0.001), whilst median eIF6 CS were significantly lower in EC (p < 0.001). Moreover, eIF5 (p = 0.002), eIF6 (p = 0.032) and eIF4g CS (p = 0.014) were significantly different when comparing NNT with EC grading types. Median eIF4g CS was higher in type II EC (p = 0.034). Upon western blot analysis, eIF4g (p < 0.001), peIF2α (p < 0.001) and eIF3h (p < 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT (p < 0.001). The remaining eIFs were non-significant. Besides tumour stage (p < 0.001) and patient's age (p < 0.001), high eIF4g CS-levels were independently associated with poor prognosis (HR: 1.604, 95%CI: 1.037-2.483, p = 0.034). The other eIFs had no prognostic significance. Notably, the independent prognostic significance of eIF4g was lost when adding tumour type. Considering the difficulties in differentiating EC type I and II, eIF4g may serve as a novel prognostic marker indicating patient outcome.

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.

Patterns of venous thromboembolism risk in patients with localized colorectal cancer undergoing adjuvant chemotherapy or active surveillance: an observational cohort study.

BACKGROUND: Venous thromoboembolism (VTE) is a frequent and burdensome complication of metastatic colorectal cancer (CRC). However, the epidemiology of VTE in patients with localized CRC after surgery in curative intent is incompletely understood. In this single-center observational cohort study, we investigate patterns of VTE risk in localized CRC, and define its relationship with baseline risk factors, adjuvant chemotherapy and CRC recurrence. METHODS: Five-hundred-sixteen patients with stage II/III CRC were included retrospectively at the time of surgery, and followed until the occurrence of VTE, CRC recurrence, or death (median age = 65.1 years, stage II and III: n = 151 (29.5%), n = 361 (70.5%); adjCTX: n = 339 (65.7%)). RESULTS: During a median follow-up of 2.7 years, 15 VTEs (2.7%) and 116 recurrences (22.5%) occurred, and 46 patients (8.9%) died. Six-month, 1-year, and 5-year VTE risks were 1.6%, 2.0% and 3.2%, respectively. In competing risk time-to-VTE regression, adjCTX was not associated with an increased risk of VTE (Subdistribution hazard ratio = 0.98, 95% CI:0.33-2.88, p = 0.97). The occurrence of disease recurrence strongly increased the risk of VTE (Multi-state model: Transition hazard ratio (THR) = 13.03, 95% CI:4.39-38.74, p < 0.0001)). Conversely, the onset of VTE did not predict for recurrence (THR = 1.95, 95% CI: 0.62-6.16, p = 0.25). CONCLUSION: VTE risk is very low in localized CRC and does not appear to be increased by adjuvant chemotherapy. Thus, primary thromboprophylaxis is unlikely to result in clinical benefit in this population. The strongest determinant of VTE risk appears to be disease recurrence.

MicroRNAs in Different Histologies of Soft Tissue Sarcoma: A Comprehensive Review.

Soft tissue sarcomas (STS) constitute a rare tumour entity comprising over 50 histological subtypes. MicroRNAs (miRNAs) are short non-protein coding RNA molecules that regulate gene expression by targeting the 3'-untranslated region of messenger RNAs. They are involved in a variety of human diseases, including malignancies, such as endometrial cancer, osteosarcoma, bronchial carcinoma and breast cancer. In STS, various miRNAs are differentially expressed, thus contributing to development, progression and invasion. Therefore, the aim of the present review is to summarise current knowledge on the role of miRNAs in STS. Furthermore, the potential role of miRNAs as diagnostic, prognostic and predictive biomarkers is discussed.