Can an artificial intelligence powered software reliably assess pelvic radiographs?

PURPOSE: Despite advances of three-dimensional imaging pelvic radiographs remain the cornerstone in the evaluation of the hip joint. However, large inter- and intra-rater variabilities were reported due to subjective landmark setting. Artificial intelligence (AI)-powered software applications could improve the reproducibility of pelvic radiograph evaluation by providing standardized measurements. The aim of this study was to evaluate the reliability and agreement of a newly developed AI algorithm for the evaluation of pelvic radiographs. METHODS: Three-hundred pelvic radiographs from 280 patients with different degrees of acetabular coverage and osteoarthritis (Tönnis Grade 0 to 3) were evaluated. Reliability and agreement between manual measurements and the outputs of the AI software were assessed for the lateral-center-edge (LCE) angle, neck-shaft angle, sharp angle, acetabular index, as well as the femoral head extrusion index. RESULTS: The AI software provided reliable results in 94.3% (283/300). The ICC values ranged between 0.73 for the Acetabular Index to 0.80 for the LCE Angle. Agreement between readers and AI outputs, given by the standard error of measurement (SEM), was good for hips with normal coverage (LCE-SEM: 3.4°) and no osteoarthritis (LCE-SEM: 3.3°) and worse for hips with undercoverage (LCE-SEM: 5.2°) or severe osteoarthritis (LCE-SEM: 5.1°). CONCLUSION: AI-powered applications are a reliable alternative to manual evaluation of pelvic radiographs. While being accurate for patients with normal acetabular coverage and mild signs of osteoarthritis, it needs improvement in the evaluation of patients with hip dysplasia and severe osteoarthritis.

Clinical impact of microbiological results in two-stage revision arthroplasty with spacer exchange.

INTRODUCTION: Patients who require a spacer exchange as part of a two-stage procedure for the treatment of periprosthetic hip and knee joint infections (PJI) have high failure rates. Little is known about the clinical impact of microbiological results and changes in the microbiological spectrum and resistance pattern in these patients. MATERIAL AND METHODS: Between 01/2011 and 12/2019, 312 patients underwent a total of 327 two-stage revision arthroplasties at our institution. A spacer exchange was required in 52/312 (16.7%) patients (27 knee/25 hip). Microbiological results, antibiotic resistance patterns, patient's host factors as well as re-revision and re-infection rates at a median follow-up of 47.8 months (range 12.2-116.7 months) were analyzed. A propensity score (PS)-matched analysis of patients who underwent spacer exchange and patients treated with standard two-stage procedure was performed. RESULTS: We found a high number of microbiological spectrum changes in patients with multiple culture positive procedures between explantations and spacer exchanges (10/12 [83.3%]), spacer exchanges and reimplantations (3/4 [75%]) as well as between reimplantations and subsequent re-revision surgeries (5/6 [83.3%]). In 9/52 (17.3%) patients, same microorganisms were detected repeatedly in two different procedures. We observed changes in the antibiotic resistance patterns in 6/9 (66.7%) of these patients. High re-infection rates were found in patients with culture positive reimplantations (10/12 [83.3%]), and low re-infection rates were found in patients with culture negative reimplantations (2/40 [5%]; p < 0.001). Between patients with and without spacer exchange, no differences were found in the re-revision rates (13/52 [25%] with vs. 13/52 [25%] without; p = 1.00) as well as re-infection rates (12/52 [23.1%] with vs. 8/52 [15.4%] without; p = 0.32). CONCLUSIONS: Changes in microbiological spectrum and antibiotic resistance patterns between stages are common in patients who require a spacer exchange. If eradication of the microorganism at reimplantation can be accomplished, comparable re-revision rates to standard two-stage procedures can be achieved.

Alpha-defensin as a diagnostic tool in revision total knee arthroplasties with unexpected positive intraoperative cultures and unexpected culture negative intraoperative cultures.

PURPOSE: Unexpected-positive-intraoperative-cultures (UPIC) are common in presumed aseptic revision-total-knee-arthroplasties (rTKA). However, the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, identification of an underlying pathogen was not possible, so-called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate the potential use of synovial alpha-defensin (AD) levels in these patients. METHODS: Synovial AD levels from 143 rTKAs were evaluated retrospectively from our prospectively maintained institutional periprostetic joint infection (PJI) biobank and database. The 2018-International Consensus Meeting (ICM) criteria was used to define the study groups. Samples from UPICs with a minimum of one positive intraoperative culture (ICM 2- ≥ 6) (n = 20) and UNIC's (ICM ≥ 6) (n = 14) were compared to 34 septic culture-positive samples (ICM ≥ 6) and 75 aseptic culture-negative (ICM 0-1). Moreover, AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) in detecting the presence of AD in native and centrifuged synovial fluid specimens was performed. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were analysed. RESULTS: AD was positive in 31/34 (91.2%) samples from the septic culture-positive group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly associated with culture positive and histopathological results (p < 0.001). No high-virulent microorganisms (0/20) were present in the UPIC group, compared to infected-group (19/34; 55.9%). High virulent microorganisms showed a positive AD result in 89.5% (17/19) of the cases. Methicillin resistant Staphylococcus epidermis (MRSE) infections had significantly higher AD levels than with methicillin susceptible S. epidermdis (MSSE) (p = 0.003). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid. CONCLUSION: AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnosis of UPIC and UNIC associated to rTKAs. Pathogen virulence as well as antibiotic resistance pattern may have an effect on AD levels. Centrifugation of synovial fluid had no influence on ADLF results.

Artificial intelligence enables reliable and standardized measurements of implant alignment in long leg radiographs with total knee arthroplasties.

PURPOSE: The purpose of this study was to evaluate the reliability of a newly developed AI-algorithm for the evaluation of long leg radiographs (LLR) after total knee arthroplasties (TKA). METHODS: In the validation cohort 200 calibrated LLRs of eight different common unconstrained and constrained knee systems were analysed. Accuracy and reproducibility of the AI-algorithm were compared to manual reads regarding the hip-knee-ankle (HKA) as well as femoral (FCA) and tibial component (TCA) angles. In the evaluation cohort all institutional LLRs with TKAs in 2018 (n = 1312) were evaluated to assess the algorithms' ability of handling large data sets. Intraclass correlation (ICC) coefficient and mean absolute deviation (sMAD) were calculated to assess conformity between the AI software and manual reads. RESULTS: Validation cohort: The AI-software was reproducible on 96% and reliable on 92.1% of LLRs with an output and showed excellent reliability in all measured angles (ICC > 0.97) compared to manual measurements. Excellent results were found for primary unconstrained TKAs. In constrained TKAs landmark setting on the femoral and tibial component failed in 12.5% of LLRs (n = 9). Evaluation cohort: Mean measurements for all postoperative TKAs (n = 1240) were 0.2° varus ± 2.5° (HKA), 89.3° ± 1.9° (FCA), and 89.1° ± 1.6° (TCA). Mean measurements on preoperative revision TKAs (n = 74) were 1.6 varus ± 6.4° (HKA), 90.5° ± 3.1° (FCA), and 88.9° ± 4.1° (TCA). CONCLUSIONS: AI-powered applications are reliable for automated analysis of lower limb alignment on LLRs with TKAs. They are capable of handling large data sets and could, therefore, lead to more standardized and efficient postoperative quality controls. LEVEL OF EVIDENCE: Diagnostic Level III.

Differential microbiological spectrum and resistance pattern in periprosthetic hip joint infections: a matched-cohort analysis comparing direct anterior versus lateral approach.

BACKGROUND: In recent years, total hip arthroplasty via the direct anterior approach (DAA) has become more common. Little is known on the influence of the surgical approach on the microbiological spectrum and resistance pattern in periprosthetic hip joint infections. The aim of the present study was to evaluate the microbiological spectrum and resistance pattern in periprosthetic hip joint infections comparing the direct anterior versus lateral approach in a matched-cohort analysis at a single institution. METHODS: Patients who underwent revision hip arthroplasty due to PJI following primary total hip arthroplasty with culture positive microbiology were analyzed. In all study patients, both the primary surgery and the revisions surgery were performed at the same institution. Only patients in whom primary surgery was performed via a direct anterior or lateral approach were included (n = 87). A matched cohort analysis was performed to compare the microbiological spectrum and resistance pattern in PJI following direct anterior (n = 36) versus lateral (n = 36) primary THA. RESULTS: We identified both a significantly different microbiological spectrum and resistance pattern in PJI comparing direct anterior versus lateral approach THA. Cutibacterium avidum was obtained more frequently in the anterior subgroup (22.2% vs. 2.8%, p = 0.028). In the subgroup of infections with Staphylococcus aureus (n = 12), methicillin resistance was detected in 3/5 cases in the direct anterior group versus 0/7 cases in the lateral group (p = 0.045). Overall, Staphylococcus epidermidis was the most common causative microorganism in both groups (direct anterior: 36.1%; lateral: 27.8%, p = 0.448). CONCLUSION: The present study indicates a potential influence of the localization of the skin incision in THA on the microbiological spectrum and resistance pattern in PJI. Cutibacterium avidum seemed to be a more common causative microorganism in PJI in patients who underwent direct anterior compared to lateral approach THA.

Incidence of lateral femoral cutaneous nerve lesions after direct anterior approach primary total hip arthroplasty - a literature review.

INTRODUCTION: Lesions of the lateral cutaneous femoral nerve are a reported complication of the direct anterior approach (DAA) for total hip arthroplasty (THA). Little is known about the incidence rates of this lesion. The goal of this study was to answer the following questions: (1) Is the true incidence rate of LFCN lesions after DAA THA known? (2) What are the reasons for the wide range of reported incidence rates in the literature? (3) Are surgeons increasingly aware of the significance of LFCN lesions? METHODS: A US Medical Library of Medicine database search was performed for DAA THA. In total, 1261 search results were screened for reported LFCN lesions. RESULTS: Forty-five studies were included reporting LFCN lesions rates of 0-83%. Subgroup analysis for studies with (group A, 6 studies, n=1113 cases) and without (group B, 39 studies n=16,741) primary focus on the LFCN lesions was performed. Incidence in group A ranged from 14.8-81% (mean 31%) and 0-83% (mean 3.8%) in group B. The difference between the groups was significant (p=0.005). No uniform and time sensitive definition of postoperative LFCN lesions was found in the literature. An analysis of the publication year and the discovered incidence rate showed an increase of incidence rates [rs=0.521 (p<0.001, two-tailed)] over time. CONCLUSION: Despite the absence of a uniform definition: LFCN lesions after DAA THA are a frequent and, in the past, often underestimated complication. LEVEL OF EVIDENCE: IV; systematic review of level II to level IV studies.

Analysis of Culture Positive First and Second Stage Procedures in Periprosthetic Knee and Hip Joint Infections.

BACKGROUND: A positive microbiological result at reimplantation may lead to a failed 2-stage revision arthroplasty in the treatment of periprosthetic joint infections. Little is known about changes in microbiological spectrum and resistance pattern between culture positive first and second stage procedures in revision knee and hip arthroplasty. METHODS: Between January 2011 and December 2019, we performed 327 two-stage revision arthroplasties on 312 patients. There were 37 of 312 (11.9%) patients (20 hips/17 knees) who had a positive microbiological culture during the first and second stage procedure. We analyzed the microbiological spectrum, antimicrobial resistance pattern, and clinical outcome of culture positive first and second stage procedures as well as subsequent re-revisions. RESULTS: Re-revision was necessary in 40.5% (15/37) of patients with culture positive first and second stage procedure at a median follow-up of 3.5 years. We found microbiological changes in 83.8% (31/37) of patients between the first and second stage and in 88.9% (8/9) between the second stage and subsequent culture positive re-revision. Polymicrobial infections were found in 21.6% (8/37) of first and in 16.2% (6/37) of second stage procedures. In 27% (10/37) of patients, microorganisms persisted between the first and second stage procedure. The antimicrobial resistance pattern changed in 60% of persistent microorganisms between the first and second stage procedure. CONCLUSION: Changes in microbiological spectrum and resistance pattern are common between culture positive first and second stage procedures as well as subsequent re-revisions. This has to be considered in the antimicrobial treatment of periprosthetic joint infections.

Wear and migration are not influenced by head size in a vitamin E-infused highly cross-linked polyethylene acetabular cup.

BACKGROUND: Aseptic loosening and periprosthetic osteolysis are frequent complications in total hip arthroplasty requiring revision surgery. Highly cross-linked polyethylene (HXLPE) implants have improved wear resistance, permitting larger femoral heads. However, such implants may experience surface cracking, mechanical failure, and oxidative damage. Vitamin E-infused HXLPE (VEPE) implants were therefore developed to reduce oxidation without compromising mechanical strength. We addressed the following questions: (1) Does femoral head size affect the midterm annual polyethylene wear rates of VEPE acetabular cups? (2) Does femoral head size affect the midterm migration rates of VEPE acetabular cups? (3) Are clinical outcomes affected by femoral head size? HYPOTHESIS: Annual wear rate, migration rate, and clinical outcomes of VEPE acetabular cups are independent of femoral head size. PATIENTS AND METHODS: This was a prospective, multicentre, observational study of patients that underwent total hip arthroplasty. Hips were grouped according to the size of femoral head implanted (28 mm, 32 mm, and 36 mm). We determined annual wear rate and migration rate of VEPE acetabular cups using the Einzel-Bild-Röntgen-Analyse software. Clinically, we assessed the Harris Hip Score and visual analog score for pain and satisfaction. RESULTS: We followed 253 patients (267 hips) for a mean of 55.0±20.6 months in the 28 mm, 46.2±21.4 months in the 32 mm, and 43.8±22.6 months in the 36 mm group. The annual wear rate was 0.025 mm per year from 1 year to the last follow-up and remained similar between the groups (p>0.05). Also, mean two-dimensional migration rates did not exceed 0.05 mm from 2 years to the last follow-up and remained similar between the groups (p=0.355). Finally, clinical outcomes also did not differ between the groups (p>0.05). Two patients required revision surgery. DISCUSSION: Femoral head size did not influence midterm annual wear rate, migration rate, and clinical outcomes of VEPE acetabular cups. Furthermore, wear and cup migration rates were below the reported values leading to osteolysis and aseptic loosening. Nevertheless, studies with extended follow-up periods will be necessary to confirm these results in the long term. LEVEL OF EVIDENCE: IV.

Survivorship and Patient-Reported Outcomes of an Uncemented Vitamin E-Infused Monoblock Acetabular Cup: A Multicenter Prospective Cohort Study.

BACKGROUND: Addition of vitamin E to polyethylene is theorized to reduce the potential for oxidative wear in acetabular components. This paper presents a multicenter prospective cohort study that reports on outcomes from use of a Vitamin E-infused highly cross-linked polyethylene acetabular cup. METHODS: Patients were recruited across nine medical institutions. Clinical outcome measures recorded were the Harris Hip Score, visual analogue score for pain and satisfaction. Evidence of implant loosening or osteolysis was collected radiologically. Cup survival and reasons for revision in relevant cases were also recorded. Data collection was undertaken preoperatively, at 6-12 weeks, 6 months, 1 year, 2 years, and 5 years. A total of 675 patients were recruited, with 450 cases available at final review. Data regarding cup survival was available to 8 years and 9 months postoperatively. RESULTS: Improvements in both the Harris Hip Score and visual analogue score for pain and satisfaction were recorded at all time points, with these being maintained through the length of follow-up. In total, 89% of cups were implanted within the Lewinnek safe zone. A lucent line was identified in one case, with no evidence of acetabular osteolysis observed throughout the follow-up period. Cup survival was 98.9% at 8 years and 9 months. No revisions for aseptic loosening were observed. CONCLUSIONS: The use of a vitamin E-infused polyethylene acetabular cup demonstrates reassuring patient-reported outcomes, radiological measures, and cup survival at medium to long-term follow-up.

LARS® band and tube for extensor mechanism reconstructions in proximal tibial modular endoprostheses after bone tumors.

UNLABELLED: Wide tumor resections around the proximal tibia (pT) are related to compromised function and high complication rates. This retrospective study aims to present the technique employed as well as functional and surgical outcomes of patients undergoing a Ligament Advanced Reinforcement System (LARS®) reconstruction of the knee extensor apparatus after tumor resection and modular endoprosthetic reconstruction of the proximal tibia. Twenty-five patients who received an artificial ligament after pT resection (11 men and 14 women; mean age, 29years; range 11 to 75years, with a minimum follow-up of 24months) were analyzed regarding the ISOLS failure mode classification. Twenty patients received LARS® during primary surgery, five patients during a revision of a pT modular endoprosthesis. LARS® was available as a band or a tube. The mean extension lag was nine degrees (range, 0 to 30°), the mean flexion was 103° (range, 60 to 130°). The mean extension lag and active flexion in primary implanted LARS were 7.8° and 101° versus secondarily implanted 45° and 115° (p<0.0001; p=0.15). Eleven out of 14 primary implanted LARS® band/tubes (71%) did well with extension lag (0 to 10°). LARS® usage as a band or as a tube showed similar results. The estimated five-year survival of LARS® was 92%. The median survival of LARS® implanted primarily was better than in the case of secondary implantation (p=0.006). Extensor mechanism reconstruction by LARS® band or tube shows excellent function and satisfactory implant survival after primary reconstruction of the extensor mechanism after proximal tibia resection. We experienced no LARS® rupture for only mechanical reasons. LEVEL OF EVIDENCE: Level IV retrospective study.

Intraoperative Diagnosis of Periprosthetic Joint Infection Using a Novel Alpha-Defensin Lateral Flow Assay.

BACKGROUND: The present study investigates the novel Synovasure periprosthetic joint infection (PJI) lateral flow test device for detection of alpha-defensin and attempts to determine its diagnostic accuracy for the intraoperative diagnosis of PJI and compares it to frozen section. METHODS: Forty consecutive patients, who underwent revision surgery, between September 2014 and September 2015 were included. The patients underwent 29 revision total knee arthroplasties and 11 revision total hip arthroplasties. Twelve patients had a confirmed PJI based on Musculoskeletal Infection Society criteria, and 28 patients were considered aseptic. RESULTS: The overall accuracy to detect PJI using the lateral flow assay was 85% (95% CI 70%-93%). The device has a positive predictive value of 80% (95% CI 44%-96%) and a negative predictive value of 87% (95% CI 68%-96%) and showed a sensitivity of 67% (95% CI 35%-89%) and specificity of 93% (95% CI 75%-99%). Frozen section had a lower sensitivity (58% [95% CI 29%-84%]) but a higher specificity (96% [95% CI 80%-100%]). Receiver operator curve analysis demonstrates an area under the curve of the Synovasure PJI Lateral Flow Test Kit and frozen section of 0.80 and 0.77, respectively. CONCLUSION: The present study suggests that the intraoperative lateral flow test is at least equivalent to intraoperative frozen section and is a useful tool to confirm the absence of PJI. Although the clinical results are promising, they are not as good as previous studies using alpha-defensin levels measured in a laboratory.

Use of diagnostic dynamic contrast-enhanced (DCE)-MRI for targeting of soft tissue tumour biopsies at 3T: preliminary results.

OBJECTIVES: To test the feasibility and accuracy of MR-guided soft tissue tumour biopsy at 3T, using the dynamic contrast-enhanced (DCE) information from staging MRI for intralesional targeting. METHODS: After obtaining written informed consent for this institutional review board-approved study, 53 patients with suspected soft tissue tumours prospectively underwent preoperative staging MRI at 3T, including DCE, and subsequent MR-guided core needle biopsy. In 44/53 cases, DCE was heterogeneous and was used for intralesional biopsy targeting. Surgical, whole-specimen histology was used as the gold standard in 43/44 patients and revealed 42 soft tissue tumours (24 men; 18 women; mean age, 52 years; range, 19 - 84). RESULTS: Final surgical histology revealed eight benign lesions, six tumours of intermediate dignity, and 28 malignancies. All malignancies had shown heterogeneous DCE. The diagnostic yield of the biopsies was 100% (42/42). Histological accuracy rates of biopsy were 100% in predicting the dignity (42/42; 95% CI [0.916 - 1.000]), 95.2% for the tissue-specific entity (40/42; 95% CI [0.847 - 0.987]), and 90.5% for the tumour grade (38/42; 95% CI [0.779 - 0.962]). CONCLUSIONS: Our preliminary study indicates that biopsy of soft tissue tumours can be performed accurately and safely with DCE targeted MR-guidance at 3T, using a combined staging/biopsy MRI protocol. KEY POINTS: • MR-guided soft tissue tumour biopsy using DCE for intralesional targeting is feasible. • Targeting by staging-MRI allows reliable planning of the biopsy approach. • The method seems accurate and safe as a combined staging/biopsy procedure in outpatients. • DCE-targeted biopsy seems useful in challenging large and heterogeneous tumours.

Multiple relapses in high-grade osteosarcoma: when to stop aggressive therapy?

The prognosis after relapse of high-grade osteosarcoma is poor and complete resection of all tumors is essential for survival. A 6-year old was diagnosed with high-grade osteosarcoma and treated according to the COSS-96 protocol. Within 5 years from initial diagnosis, five osteosarcoma relapses occurred and every time it was possible to achieve complete surgical remission. Additional treatments included chemotherapy and dendritic cell-based cancer immune therapy. Since the end of therapy of the 5th relapse, he is alive for 11½ years. Our experience further supports that aggressive surgery can help to achieve long-term survival even in patients with multiple osteosarcoma relapses.

Tumour response of osteosarcoma to neoadjuvant chemotherapy evaluated by magnetic resonance imaging as prognostic factor for outcome.

PURPOSE: This study evaluated the feasibility of computed magnetic resonance imaging (MRI) volumetry in conventional osteosarcomas. Secondly, we investigated whether computed volumetry provides new prognostic indicators for histological response of osteosarcomas after neoadjuvant chemotherapy. METHODS: In a retrospective cohort study, data from the Vienna Bone Tumour Registry was used. MR images from 14 patients (male:female = 1.8, mean age 19 years) were analysed prior to and after neoadjuvant chemotherapy according to current therapy regimens. Histological response to chemotherapy was graded according to the Salzer-Kuntschik classification. Computed volumetry was performed for the intraosseous part, as well as the soft-tissue component and the tumour as a whole. RESULTS: In a setting of appropriate radiological equipment, the method has been considered to be well implementable into clinical routine. The mean tumour volume prior to chemotherapy was 321 (±351) ml. In good responders (n = 6), overall tumour volume decreased by 47% (p = 0.345), whereas poor responders (n = 8) showed a 19% decrease (p = 0.128). Neoadjuvant multidrug therapy remarkably changed the tumour composition. This is seen in a decrease of the mean ratio of soft-tissue to intraosseous tumour volume from 8.67 in poor responders and 1.15 in good responders to 1.26 and 0.45 (p = 0.065), respectively. Interestingly, the bony compartment of good responders showed a volume increase during neoadjuvant chemotherapy (p = 0.073). However, we did not find prognostic markers for histological tumour response to pre-operative chemotherapy. CONCLUSIONS: Separated volumetry of tumour segments revealed interesting insights into therapy-induced growth patterns. If verified in a larger study population, these results should be taken into account when planning ablative surgery.

Peripheral nerve tractography in soft tissue tumors: a preliminary 3-tesla diffusion tensor magnetic resonance imaging study.

INTRODUCTION: This diffusion tensor magnetic resonance imaging (DTI) study aimed to clarify the relationship of peripheral nerves and soft tissue tumors (STTs) in 3D to optimize subsequent treatment. METHODS: Twenty-six consecutive STT patients (histologically malignant, n=10; intermediate, n=3; and benign, n=13) underwent 3-Tesla MRI using an echoplanar DTI sequence. Deterministic tractography was performed. Fractional anisotropy (FA) values were measured within peritumoral and distant regions of interest. RESULTS: Tractography depicted the 3D course of the sciatic (n=12), femoral (n=2), tibial (n=7), fibular (n=2), median (n=1), musculocutaneous (n=1), and ulnar (n=1) nerves in a regular (n=8 of 18, 44.4%) or thinned (n=7 of 18, 38.9%) fashion. The lowest peritumoral FA values, abrupt thinning, and/or complete discontinuity of trajectories were found in 2 cases with histologically proven tumoral nerve infiltration. CONCLUSIONS: DTI clarifies the 3D topography between major peripheral nerves and STTs and may be helpful in the assessment of peripheral nerve infiltration by malignant tumors.

Incidence and management of hip dislocation in tumour patients with a modular prosthesis of the proximal femur.

PURPOSE: Little data is available about the incidence and especially the management of hip dislocation following the implantation of modular tumor prostheses of the proximal femur. In this retrospective single-centre study we assessed the incidence of hip dislocation following implantation of a proximal femoral modular prosthesis as well as the success of the subsequent surgical or non-surgical treatment in tumor patients. METHODS: Between 1982 and 2008, 166 tumor patients received a modular prosthesis of the proximal femur at our institution. The average age at the time of surgery was 50 ± 20 years (range, six to 84 years). An additional pelvic reconstruction was done in 14 patients. An artificial band for soft tissue reconstruction of the hip was used in 19 patients. The average time of follow-up was 46 ± 64 months (range, one to 277 months). RESULTS: The overall dislocation rate after proximal femoral replacement was 13% after a mean time of seven ± eight months (range, 0.3-33 months) after surgery. Between 1982 and 1986 the dislocation rate was 33% and declined to 9% in subsequent years (1987-2008). Patients who had received an additional pelvic reconstruction had a three fold higher dislocation rate (p <0.05). Patients with closed reduction had a 58% (eight of 12) re-dislocation rate compared to 11% (one of nine) for open reduction (p = 0.0357). CONCLUSIONS: Dislocation of a modular prosthesis of the proximal femur is a common complication, especially in cases with additional pelvic resection with extensive bone and soft-tissue defects. Open surgical management may be more effective in preventing re-dislocation than closed reduction and bracing alone.

Effects of denosumab on pain and analgesic use in giant cell tumor of bone: interim results from a phase II study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an aggressive primary osteolytic tumor. GCTB often involves the epiphysis, usually causing substantial pain and functional disability. Denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κΒ ligand (RANKL), is an effective treatment option for patients with advanced GCTB. This analysis of data from an ongoing, open-label study describes denosumab's effects on pain and analgesic use in patients with GCTB. MATERIAL AND METHODS: Patients with unresectable disease (e.g. sacral or spinal GCTB, or multiple lesions including pulmonary metastases) were enrolled into Cohort 1 (N = 170), and patients with resectable disease whose planned surgery was associated with severe morbidity (e.g. joint resection, limb amputation, or hemipelvectomy) were enrolled into Cohort 2 (N = 101). Patients received denosumab (120 mg) subcutaneously every four weeks, with additional doses on study days 8 and 15. Patients assessed worst pain severity with the Brief Pain Inventory - Short Form (BPI-SF) at baseline, at each visit for the first six months, and every three months thereafter. RESULTS: Clinically relevant pain improvement was reported by 29% of patients in Cohort 1 and 35% in Cohort 2 during week 1 and by ≥ 50% of patients in each cohort at each study visit from months 2-30. Median time to clinically relevant improvement was 30 (95% CI 16, 57) days in Cohort 1 and 15 (95% CI 15, 29) days in Cohort 2. Results in patients with moderate/severe pain at baseline were similar. Fewer than 30% of patients in Cohort 1 and 10% in Cohort 2 experienced clinically relevant pain worsening at any visit through 27 months. Most patients had no/low analgesic use during the study. CONCLUSION: Most patients treated with denosumab experienced clinically relevant decreases in pain within two months.

Altered matrix mineralization in a case of a sclerosing osteosarcoma.

Little is known about the tumor matrix mineralization of highly sclerotic osteosarcoma. We used quantitative backscattered electron imaging (qBEI) to determine the Bone mineralization density distribution (BMDD) of a highly sclerosing osteosarcoma of the proximal tibia as well as adjacent normal bone of a 10-year-old girl following chemotherapy according to the EURAMOS-1 protocol. Data were compared to recently published normative reference data for young individuals. Backscattered electron imaging of the tumor region revealed a dense accumulation of mineralized tumor bone matrix (up to 90% of the medullar space). The BMDD was shifted tremendously towards higher matrix mineralization (CaMean +18.5%, CaPeak +22.5%, CaHigh +100 fold) compared to normal bone. Additionally the BMDD became much wider, indicating a higher heterogeneity in mineralization (CaWidth +40%). In contrast to lamellar bone, which mineralizes via a mineralization front, the mineralization of the tumor matrix starts by randomly distributed spots of mineral clusters fusing together to a highly mineralized non-lamellar bone matrix. We also found an altered BMDD of the patient's normal bone when compared with the reference BMDD of young individuals. In conclusion this high radiodensity region of the sclerosing sarcoma is not only due to the high amount of tumor matrix but also to its high mineralization density. Chemotherapy may lead to altered matrix mineralization of normal bone due to suppression of bone turnover. The mechanism of matrix mineralization in a sclerosing osteosarcoma warrants further studies.

Modular prosthetic reconstruction of major bone defects of the distal end of the humerus.

BACKGROUND: Bone defects of the distal end of the humerus require complex reconstructions, for which standard prostheses may be insufficient. We investigated the outcomes of distal humeral reconstruction with use of a modular prosthesis. METHODS: Fifty-three elbows in fifty-two patients underwent reconstruction with a modular prosthesis (twelve total humeral replacements and forty-one distal humeral replacements) after tumor resection (thirty-eight elbows) or because of massive joint degeneration (fifteen elbows). In the tumor group, twenty-three patients (twenty-four elbows) had metastatic disease and fourteen had a primary tumor. Degenerative defects of the distal end of the humerus were caused by pseudarthrosis (six elbows), prosthetic failure (five), trauma (two), osteomyelitis (one), and supracondylar fracture (one). The mean duration of follow-up for all patients was twenty-eight months (median, thirteen months; range, one to 219 months). RESULTS: The mean Inglis-Pellicci score in the tumor group was 84 points, and the mean Musculoskeletal Tumor Society score was 78%. Patients with total humeral reconstruction had worse scores than those with distal humeral reconstruction. Twenty-four patients died of disease at a mean of thirteen months after surgery. Local tumor control was achieved in all patients. In the revision group, the mean Inglis-Pellicci score was 76 points. The Inglis-Pellicci score was significantly better for patients in the tumor group. Eight patients (15%) had a deep periprosthetic infection, requiring amputation in one patient (2%) and prosthetic removal in two patients (4%). Four patients (8%) had the implants revised for aseptic loosening. CONCLUSIONS: Modular prostheses of the distal end of the humerus provide a stable reconstruction of the elbow with satisfactory function and disease control in patients with a tumor, but careful patient selection is required when the prostheses are used for revision surgery in patients without a tumor.