Publications by authors named "Boris Michael Holzapfel"

41 Publications

Primary hip arthroplasty via the direct anterior approach.

Oper Orthop Traumatol 2021 08 12;33(4):287. Epub 2021 Aug 12.

Department of Orthopedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

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http://dx.doi.org/10.1007/s00064-021-00725-8DOI Listing
August 2021

[Primary hip arthroplasty via the direct anterior approach - German version].

Oper Orthop Traumatol 2021 08 12;33(4):285-286. Epub 2021 Aug 12.

Klinik für Orthopädie und Unfallchirurgie, Muskuloskelettales Universitätszentrum München (MUM), Universitätsklinikum, LMU München, Marchioninistr. 15, 81377, München, Deutschland.

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http://dx.doi.org/10.1007/s00064-021-00726-7DOI Listing
August 2021

Direct anterior approach for total hip arthroplasty using the "bikini incision".

Oper Orthop Traumatol 2021 Aug 2;33(4):318-330. Epub 2021 Aug 2.

Department of Orthopedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Objective: The classic skin incision for direct anterior approach (DAA) total hip arthroplasty (THA) is usually placed over the belly of the tensor fasciae latae (TFL) muscle parallel to the axis of the lower extremity. In the "bikini incision" technique however, a more horizontal skin incision is used and placed parallel to the skin creases, which largely corresponds to the skin's tension lines to prevent hypertrophic scarring and optimize cosmetic outcomes.

Indications: Primary or secondary osteoarthritis, femoral neck fracture, aseptic acetabular component loosening with sufficient bone stock and without the need for proximal extension of the approach, head and/or liner exchange.

Contraindications: Complex primary or revision THA requiring extensile distal and/or acetabular exposure, revision with pre-existing longitudinal DAA incision, inguinal skin infection.

Surgical Technique: The skin incision, located three fingerbreadths distal to the anterior superior iliac spine (ASIS), is orientated parallel to the groin crease. One third of the incision is medial and two thirds lateral to the ASIS. Subcutaneous dissection should only be performed in the lateral two thirds of the incision to protect the main branches of the lateral femoral cutaneous nerve (LFCN). The fascia lata is opened as far lateral over the muscle belly as possible to leave the LFCN untouched within its fascial sheet. The stepwise procedure consists of three key steps: capsular exposure, capsular release, and component insertion. The approach allows for an excellent 360° exposure of the acetabulum. The femur is aligned along the incision during femoral elevation and adduction. With this technique, DAA hip arthroplasty can be performed in a less-invasive way providing best possible functional and cosmetic outcomes.

Postoperative Management: No restrictions in ambulation or range of motion. Deep vein thrombosis prophylaxis.

Results: In a prospective series of 532 consecutive patients undergoing 613 primary THA with a bikini-incision in 2017, a good clinical outcome with a 2.3% incidence of wound-related problems was observed. In particular, obese patients can also benefit from the technique.
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http://dx.doi.org/10.1007/s00064-021-00721-yDOI Listing
August 2021

Short stem hip arthroplasty via the minimally invasive direct anterior approach.

Oper Orthop Traumatol 2021 Aug 12;33(4):288-303. Epub 2021 Jul 12.

Department of Orthopaedic Surgery, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstr. 11, 97074, Wuerzburg, Germany.

Objective: Tissue-sparing, minimally invasive hip arthroplasty via the direct anterior approach (DAA) using a partially neck-preserving, calcar-guided short stem.

Indications: Primary and secondary osteoarthritis of the hip due to developmental dysplasia, femoroacetabular impingement, femoral head necrosis or trauma sequelae.

Contraindications: Severe osteoporosis, active infection, American Society of Anesthesiologists (ASA) > III, large metaphyseal bone defects, severe metaphyseal deformities, Dorr type C femur.

Surgical Technique: Supine position on a standard operating table without extension device. Classic DAA skin incision or bikini incision distal to the inguinal fold. Blunt dissection entering the Hueter interval. Capsulotomy with capsule preservation or partial capsulectomy. Intraoperatively, it is crucial to adhere to the preoperatively planned angle and height of the femoral neck osteotomy. During femoral head removal and acetabular preparation, care must be taken to avoid iatrogenic damage to the remaining neck. After cup positioning, femoral access is achieved by release of superior capsular structures. During opening of the medullary canal and broaching, femoral torsion and axis have to be taken into account for correct rotational and axial alignment. Femoral broaches are inserted in an ascending series of sizes until the last broach is firmly lodged and is in direct contact with the antero-medial femoral neck cortex. Fluoroscopic control in two planes to check for femoral anatomic and overall offset and assess whether the implant is adequately seated with cortical support at the calcar, the distal lateral and the dorsal cortex. Implantation of the definitive implants, local infiltration analgesia and wound closure.

Results: Between 1/2011 and 12/2016 60 patients (24 female, 36 male; mean age 44 years) were treated with a partially neck-preserving short stem via the described approach. Seven patients underwent a bi-lateral procedure. Thus, 67 procedures were analysed in this retrospective cohort study. Mean follow-up was 70 months (range 28-93). The median Harris Hip Score was 48 (range 11-88) preoperatively and 98 (range 80-100) postoperatively.

Conclusion: The minimally invasive implantation of a partially neck-preserving stem via DAA provides a safe technique with good to excellent clinical results in the mid-term.
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http://dx.doi.org/10.1007/s00064-021-00723-wDOI Listing
August 2021

Custom Made Monoflange Acetabular Components for the Treatment of Paprosky Type III Defects.

J Pers Med 2021 Apr 8;11(4). Epub 2021 Apr 8.

Department of Orthopaedic Surgery, Orthopädische Klinik König-Ludwig-Haus, University of Wuerzburg, 97070 Wuerzburg, Germany.

Purpose: Patient-specific, flanged acetabular components are used for the treatment of Paprosky type III defects during revision total hip arthroplasty (THA). This monocentric retrospective cohort study analyzes the outcome of patients treated with custom made monoflanged acetabular components (CMACs) with intra- and extramedullary iliac fixation.

Methods: 14 patients were included who underwent revision THA with CMACs for the treatment of Paprosky type III defects. Mechanism of THA failure was infection in 4 and aseptic loosening in 10 patients. Seven patients underwent no previous revision, the other seven patients underwent three or more previous revisions.

Results: At a mean follow-up of 35.4 months (14-94), the revision rate of the implant was 28.3%. Additionally, one perioperative dislocation and one superficial wound infection occurred. At one year postoperatively, we found a significant improvement of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score ( = 0.015). Postoperative radiographic analysis revealed good hip joint reconstruction with a mean leg length discrepancy of 3 mm (-8-20), a mean lateralization of the horizontal hip center of rotation of 8 mm (-8-35), and a mean proximalization of the vertical hip center of rotation of 6 mm (13-26). Radiolucency lines were present in 30%.

Conclusion: CMACs can be considered an option for the treatment of acetabular bone loss in revision THA. Iliac intra- and extramedullary fixation allows soft tissue-adjusted hip joint reconstruction and improves hip function. However, failure rates are high, with periprosthetic infection being the main threat to successful outcome.
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http://dx.doi.org/10.3390/jpm11040283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068245PMC
April 2021

Revision Arthroplasty Through the Direct Anterior Approach Using an Asymmetric Acetabular Component.

J Clin Med 2020 Sep 21;9(9). Epub 2020 Sep 21.

Department of Orthopaedic Surgery, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074 Wuerzburg, Germany.

Despite increasing numbers of primary hip arthroplasties performed through the direct anterior approach (DAA), there is a lack of literature on DAA revision arthroplasty. The present study was performed in order to evaluate outcomes and revision rates after revision through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation. In a retrospective cohort study, we analyzed prospectively collected data of 57 patients (61 hips, 43 female, 18 male) who underwent aseptic acetabular component revision through the DAA with the abovementioned implant system between January 2015 and December 2017. The mean follow-up was 40 months (12-56). Survival rates were estimated using the Kaplan-Meier method. All complications were documented and functional outcomes were assessed pre- and postoperatively. Kaplan-Meier analysis revealed an estimated five-year implant survival of 97% (confidence interval CI 87-99%). The estimated five-year survival with revision for any cause was 93% (CI 83-98%). The overall revision rate was 6.6% (n = 4). Two patients had to undergo revision due to periprosthetic infection (3.3%). In one patient, the acetabular component was revised due to aseptic loosening four months postoperatively. Another patient suffered from postoperative iliopsoas impingement and was treated successfully by arthroscopic iliopsoas tenotomy. Two (3.3%) of the revised hips dislocated postoperatively. The mean Harris Hip Score improved from 35 (2-66) preoperatively to 86 (38-100) postoperatively ( < 0.001). The hip joint's anatomical center of rotation was restored at a high degree of accuracy. Our findings demonstrate that acetabular revision arthroplasty through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation is safe and practicable, resulting in good radiographic and clinical midterm results.
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http://dx.doi.org/10.3390/jcm9093031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564155PMC
September 2020

Acetabular Revision With Intramedullary and Extramedullary Iliac Fixation for Pelvic Discontinuity.

J Arthroplasty 2020 12 30;35(12):3679-3685.e1. Epub 2020 Jun 30.

Department of Orthopaedic Surgery, University of Wuerzburg, Wuerzburg, Germany; Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.

Background: Parallel to the increase in revision hip procedures surgeons face more and more complex anatomical challenges with pelvic discontinuity (PD) being one of the worst-case scenarios. Here we report on our clinical results using an asymmetric acetabular component for the treatment of PD. The implant is armed in a monoblock fashion with an extramedullary iliac flange and provides the possibility to augment it with an intramedullary iliac press-fit stem.

Methods: In a single-center retrospective cohort study we analyzed prospectively collected data of 49 patients (35 female, 14 male) suffering from unilateral periprosthetic PD treated with an asymmetric acetabular component between 2009 and 2017. The mean follow-up was 71 months (21-114). Complications were documented and radiographic and functional outcomes were assessed.

Results: Kaplan-Meier analysis revealed a 5-year implant survival of 91% (confidence interval 77%-96%). The 5-year survival with revision for any cause was 87% (CI 74%-94%). The overall revision rate was 16% (n = 8). Two patients required acetabular component revision due to aseptic loosening. Four patients (8%) suffered from periprosthetic infection: one patient was treated with a 2-stage revision, and another one with resection arthroplasty. The other 2 patients were treated with debridement, irrigation, and exchange of the mobile parts. Of 6 patients (12%) suffering from hip dislocation, 2 required implantation of a dual mobility acetabular component. The mean Harris Hip Score improved from 41 preoperatively to 79 at the latest follow-up (P < .001).

Conclusion: Our findings demonstrate that an asymmetric acetabular component with extramedullary and optional intramedullary iliac fixation is a reliable and safe treatment method for periprosthetic PD resulting in good clinical and radiographic mid-term results.
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http://dx.doi.org/10.1016/j.arth.2020.06.067DOI Listing
December 2020

The 2019 Austrian-Swiss-German Traveling Fellowship.

J Bone Joint Surg Am 2020 Sep;102(18):e105

Department of Orthopaedic Surgery, Julius-Maximilians-University Wuerzburg, Wuerzburg, Germany.

The Austrian-Swiss-German (ASG) Traveling Fellowship was established over 40 years ago as an annual exchange program between the English-speaking countries of the United States, Great Britain, and Canada and the German-speaking countries of Austria, Germany, and Switzerland. In 2019, 4 German-speaking consultant orthopaedic surgeons represented their national societies in this unique and prestigious fellowship program: Karlmeinrad Giesinger from the St. Gallen Hospital, sponsored by the Swiss Society of Orthopaedics and Traumatology; Boris Michael Holzapfel from the Julius-Maximilians University in Wuerzburg, and Georgi Wassilew from the Greifswald Medical University, both sponsored by the German Society for Orthopaedics and Traumatology; and Martin Thaler from the Medical University of Innsbruck, sponsored by the Austrian Orthopaedic Association. This article describes the 2019 ASG Traveling Fellowship.
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http://dx.doi.org/10.2106/JBJS.20.00764DOI Listing
September 2020

Revision arthroplasty with rotating hinge systems for total knee arthroplasty instability.

Oper Orthop Traumatol 2020 Aug 29;32(4):298-308. Epub 2020 May 29.

Department of Orthopaedic Surgery, Orthopädische Klinik König-Ludwig-Haus, Julius-Maximilians-University Würzburg, Brettreichstr. 11, 97074, Würzburg, Germany.

Objective: Restoring stability after total knee arthroplasty (TKA) and improving joint function using a cemented rotating hinge system.

Indications: Ligament instability and/or osseous defects (including Anderson Orthopaedic Research Institute [AORI] classification type II defects) after primary TKA or TKA revision surgery.

Contraindications: Distal femoral or proximal tibial bowing requiring implant systems that provide femoral or tibial offset stems. Persistent periprosthetic infection. Poor therapeutic compliance. AORI type III defects.

Surgical Technique: Medial arthrotomy. Femoral and tibial component removal with small saw blades and chisels. Intramedullary alignment for the tibial and femoral cuts. Debridement and removal of membranes and cement remnants. Reconstruction of joint line and correct TKA alignment. Trial reduction. Cement fixation.

Postoperative Management: Unrestricted range of motion, partial weight bearing for 4 weeks.

Results: Between 2012 and 2013, 18 patients suffering from ligament insufficiency after TKA were revised using the described system and included in a prospective study protocol. The mean follow-up was 37 months (range 30-46 months). There was a significant improvement of the Oxford Knee Score (OKS) from 19 (range 7-29) preoperatively to 29 (range 10-45) postoperatively (p = 0.004). The Knee Society Score (KSS) knee assessment subscore improved from 35 (range 9-70) to 67 (range 35-97) (p = 0.002) and the pain score from 7 (range 0-50) to 24 (range 0-50) (p = 0.008).
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http://dx.doi.org/10.1007/s00064-020-00663-xDOI Listing
August 2020

Revision of unicompartmental knee arthroplasty using the in situ referencing technique.

Oper Orthop Traumatol 2020 Aug 5;32(4):273-283. Epub 2020 Mar 5.

Department of Orthopaedic Surgery, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstr. 11, 97074, Wuerzburg, Germany.

Objective: Revision of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA) with the in situ referencing technique aiming to preserve as much ligament function and epi-metaphyseal bone stock as possible.

Indications: Aseptic loosening, progression of osteoarthritis, periprosthetic fracture, periprosthetic infection, arthrofibrosis, polyethylene wear, malalignment, instability, femoro-tibial impingement.

Contraindications: Unexplained pain, localized or systemic active infection (anywhere).

Surgical Technique: Referencing for the tibia and the femur cuts is performed prior to implant removal. The tibial cutting jig and the initial tibial resection level is set in a way that the sawblade just fits under the tibial implant. In case too much bone needs to be removed to achieve flush implant sitting on both the medial and lateral tibia, a step cut needs to be performed to build up the medial defect with an augment. Prior to femoral component removal, rotational alignment is determined and intramedullary referencing for the distal femur osteotomy is performed. Level of constraint and additional tibial stem fixation is chosen according to the amount of bone resected and according to ligament stability.

Postoperative Management: Sterile dressings and elastic compression bandaging. No limitation of active/passive range of motion. Full weight-bearing or partial weight-bearing for 2 weeks postoperatively in the presence of bone or soft tissue defects.

Results: Between 2008 and 2019, 84 patients underwent revision of unicompartmental knee arthroplasty. The mean follow-up was 64 months (range 3-132 months). Implant survival after revision of UKA to TKA was 92% (95% CI = 82-97%) at 5 years of follow-up and 86% (95% CI = 69-93%) at 10 years of follow-up. The mean Oxford knee score was 20.1 (6-39, SD ± 6.5) preoperatively and 30.2 (3-48, SD ± 11.3) postoperatively. The mean visual analogue scale was 6.9 (range 1-10, SD ± 1.8) preoperatively and 3.9 (range 0-9, SD ± 2.6) postoperatively.
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http://dx.doi.org/10.1007/s00064-020-00656-wDOI Listing
August 2020

Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity.

Calcif Tissue Int 2019 09 18;105(3):331-340. Epub 2019 Jun 18.

Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia.

This study aimed to investigate the effects of recombinant human bone morphogenetic protein (rhBMP-7) on human cancellous bone grafts (BGs) while differentiating between anabolic and catabolic events. Human BGs alone or supplemented with rhBMP-7 were harvested 14 weeks after subcutaneous implantation into NOD/Scid mice, and studied via micro-CT, histomorphometry, immunohistochemistry and flow cytometry. Immunohistochemical staining for human-specific proteins made it possible to differentiate between grafted human bone and newly formed murine bone. Only BGs implanted with rhBMP-7 formed an ossicle containing a functional hematopoietic compartment. The total ossicle volume in the BMP group was higher than in the BMP group (835 mm vs. 365 mm, respectively, p < 0.001). The BMP group showed larger BM spaces (0.47 mm vs. 0.28 mm, p = 0.002) and lower bone volume-to-total volume ratio (31% vs. 47%, p = 0.002). Immunohistochemical staining for human-specific proteins confirmed a higher ratio of newly formed bone area (murine) to total area (0.12 vs. 0.001, p < 0.001) in the BMP+ group, while the ratio of grafted bone (human) area to total area was smaller (0.14 vs. 0.34, p = 0.004). The results demonstrate that rhBMP-7 induces BG resorption at a higher rate than new bone formation while creating a haematopoietic niche. Clinicians therefore need to consider the net catabolic effect when rhBMP-7 is used with BGs. Overall, this model indicates its promising application to further decipher BMPs action on BGs and its potential in complex bone tissue regeneration.
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http://dx.doi.org/10.1007/s00223-019-00574-5DOI Listing
September 2019

Evaluation of implant fit and frontal plane alignment after bi-compartmental knee arthroplasty using patient-specific instruments and implants.

Arch Med Sci 2018 Oct 23;14(6):1424-1431. Epub 2018 Oct 23.

Department of Orthopaedic Surgery, König-Ludwig-Haus, Julius-Maximilians-University, Würzburg, Germany.

Introduction: The goals of successful bi-compartmental knee arthroplasty are to achieve correct fit and positioning of the implant, while appropriately correcting the mechanical alignment of the leg after surgery. As these requirements are not always reliably fulfilled using off-the-shelf implant systems, newer approaches for bi-compartmental resurfacing have been explored.

Material And Methods: In this article we report the radiographic results of 30 patients with anteromedial osteoarthritis (OA) who were treated with a novel patient-specific fixed-bearing bi-compartmental knee resurfacing system using custom-made implants and instruments. Utilizing standardized pre- and postoperative radiographic analyses (based on anterior-posterior and lateral, anterior-posterior weight-bearing full-length radiographs, patella skyline views and preoperative computed tomography (CT) scanning) implant fit and positioning as well as correction of the mechanical axis (hip-knee-ankle angle, HKA) were determined.

Results: On average, HKA was corrected from 173.4 ±3.47° preoperatively to 179.4 ±2.85° postoperatively. The coronal femoro-tibial angle was corrected on average 5.61°. The preoperative tibial slope measured on lateral views was 6.38 ±2.4°, while the average slope in the CT-based planning protocol (iView) was 6.14 ±2.40°. Postoperative lateral tibial slope was determined to be 5.77 ±1.97°. The thickness of the posterior femoral cuts was measured intraoperatively and, in all cases, corresponded well to the targeted thickness of the cuts provided by the iView. The joint line was preserved in all cases and the average Insall-Salvati index was 1.078 ±0.11 pre- and 1.072 ±0.11 postoperatively. The fit of the implant components measured by over- or underhang was excellent throughout (< 1.01 mm).

Conclusions: Custom-made bicompartmental knee arthroplasty can ensure optimized fitting and positioning of the implant with restoration of the leg axis. These implants could be considered as an alternative primary solution for knee surgeons treating bi-compartmental disease.
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http://dx.doi.org/10.5114/aoms.2018.79007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209715PMC
October 2018

High Prevalence of Vitamin D Deficiency in Patients with Bone Tumors.

Cancer Invest 2017 Sep 11;35(8):562-568. Epub 2017 Aug 11.

a Department of Orthopedics , Koenig-Ludwig-Haus, University of Wuerzburg , Wuerzburg , Germany.

The aim of this study was to evaluate the prevalence of vitamin D deficiency in patients with different types of bone tumors and to elucidate whether or not there are differences in prediagnostic vitamin D levels in patients with malignant compared to benign bone tumors. Prediagnostic serum 25(OH)D levels of 105 consecutive patients that presented with bone tumors and tumor-like lesions to two Orthopedic Level I University Centers in Germany between 2011 and 2016 were measured on admission. We found an alarming and widespread rate of vitamin D deficiency in patients with bone tumors. Specifically, 83% of all patients had low vitamin D levels with a mean 25(OH)D level of 19.82 ng/ml. Notably, patients diagnosed with malignant bone tumors had significantly lower vitamin D levels compared to patients with benign bone lesions (p = 0.0008). In conclusion, it is essential to assess vitamin D levels in patients with tumors involving bone. In addition, there might be an association between vitamin D deficiency and the onset or course of primary malignant bone tumors.
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http://dx.doi.org/10.1080/07357907.2017.1351985DOI Listing
September 2017

Lycopene reduces ovarian tumor growth and intraperitoneal metastatic load.

Am J Cancer Res 2017 1;7(6):1322-1336. Epub 2017 Jun 1.

Queensland University of Technology (QUT)60 Musk Avenue, Kelvin Grove, QLD 4059, Brisbane, Australia.

Mutagens like oxidants cause lesions in the DNA of ovarian and fallopian tube epithelial cells, resulting in neoplastic transformation. Reduced exposure of surface epithelia to oxidative stress may prevent the onset or reduce the growth of ovarian cancer. Lycopene is well-known for its excellent antioxidant properties. In this study, the potential of lycopene in the prevention and treatment of ovarian cancer was investigated using an intraperitoneal animal model. Lycopene prevention significantly reduced the metastatic load of ovarian cancer-bearing mice, whereas treatment of already established ovarian tumors with lycopene significantly diminished the tumor burden. Lycopene treatment synergistically enhanced anti-tumorigenic effects of paclitaxel and carboplatin. Immunostaining of tumor and metastatic tissues for Ki67 revealed that lycopene reduced the number of proliferating cancer cells. Lycopene decreased the expression of the ovarian cancer biomarker, CA125. The anti-metastatic and anti-proliferative effects were accompanied by down-regulated expression of and EMT markers, decreased protein expression of integrin α5 and reduced activation of MAPK. These findings indicate that lycopene interferes with mechanisms involved in the development and progression of ovarian cancer and that its preventive and therapeutic use, combined with chemotherapeutics, reduces the tumor and metastatic burden of ovarian cancer .
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489781PMC
June 2017

Tissue engineering and regenerative medicine in musculoskeletal oncology.

Cancer Metastasis Rev 2016 09;35(3):475-87

Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4049, Australia.

Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration. At the same time, precautionary measures have to be taken when these instruments are used in cancer patients to prevent any promotion of tumour growth or metastatic spread. On the other hand, several innovative TE&RM tools are being developed such as multi-functionalized biomaterials, drug-delivering nanomaterials or genetically engineered stem cells that per se have the potential to mediate anti-cancer effects, act synergistically with currently used chemotherapeutics and/or radiotherapy regimens and reduce their side effects. Recently, scientists became conscious that TE&RM strategies may not only be utilized to advance contemporary tissue reconstruction techniques but also to develop personalized diagnostic tools and clinically relevant disease models for cancer patients. Eventually, prospective randomized clinical trials combined with comparative outcome analyses are a conditio sine qua non to shape the benefits of personalized regenerative therapies for the standardized management of patients with musculoskeletal tumours.
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http://dx.doi.org/10.1007/s10555-016-9635-zDOI Listing
September 2016

Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model.

PLoS One 2016 25;11(7):e0159669. Epub 2016 Jul 25.

Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, D-81675, München, Germany.

Low molecular weight heparin (LMWH) is routinely used to prevent thromboembolism in orthopaedic surgery, especially in the treatment of fractures or after joint-replacement. Impairment of fracture-healing due to increased bone-desorption, delayed remodelling and lower calcification caused by direct osteoclast stimulation is a well-known side effect of unfractioned heparin. However, the effect of LMWH is unclear and controversial. Recent studies strongly suggest impairment of bone-healing in-vitro and in animal models, characterized by a significant decrease in volume and quality of new-formed callus. Since October 2008, Rivaroxaban (Xarelto) is available for prophylactic use in elective knee- and hip-arthroplasty. Recently, some evidence has been found indicating an in vitro dose independent reduction of osteoblast function after Rivaroxaban treatment. In this study, the possible influence of Rivaroxaban and Enoxaparin on bone-healing in vivo was studied using a standardized, closed rodent fracture-model. 70 male Wistar-rats were randomized to Rivaroxaban, Enoxaparin or control groups. After pinning the right femur, a closed, transverse fracture was produced. 21 days later, the animals were sacrificed and both femora harvested. Analysis was done by biomechanical testing (three-point bending) and micro CT. Both investigated substances showed histomorphometric alterations of the newly formed callus assessed by micro CT analysis. In detail the bone (callus) volume was enhanced (sign. for Rivaroxaban) and the density reduced. The bone mineral content was enhanced accordingly (sign. for Rivaroxaban). Trabecular thickness was reduced (sign. for Rivaroxaban). Furthermore, both drugs showed significant enlarged bone (callus) surface and degree of anisotropy. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159669PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959754PMC
July 2017

Lycopene's Effects on Cancer Cell Functions within Monolayer and Spheroid Cultures.

Nutr Cancer 2016 25;68(2):350-63. Epub 2016 Mar 25.

a Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane , Australia.

Lycopene, a compound that blocks the action of free radicals and oxygen molecules, is found in tomatoes and tomato-based products and linked to a reduced incidence of cancer. Increasing willingness of patients to maintain a healthy lifestyle by supplemental intake of nutrients and acceptance of alternative therapeutics has boosted research into nutraceuticals. The potential of lycopene to prevent or treat cancer has been investigated, but outcomes are inconsistent and its mode of action is still unknown. Further studies are needed to understand the role of lycopene in cancer prevention and treatment. The impact of lycopene on viability, proliferation, migration, and invasion of five different cancer cell lines was determined using monolayer and spheroid cultures. Cell viability was significantly reduced upon lycopene treatment at physiologically attainable concentrations. Cell proliferation, migration, and invasion did not change upon lycopene treatment. Ovarian cancer spheroids initially showed a decreased proliferation and after 14 days increased cell viability upon lycopene treatment, confirming the potential of lycopene to reduce cancer cell growth in short-term cultures and also indicate enhanced cell viability over prolonged exposure. This study cannot substantiate that lycopene inhibits cell functions associated with tumor growth, even in a 3D cancer model that mimics the natural tumor microenvironment.
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http://dx.doi.org/10.1080/01635581.2016.1150498DOI Listing
December 2016

The Wuerzburg procedure: the tensor fasciae latae perforator is a reliable anatomical landmark to clearly identify the Hueter interval when using the minimally-invasive direct anterior approach to the hip joint.

BMC Musculoskelet Disord 2016 Feb 3;17:57. Epub 2016 Feb 3.

Department of Orthopaedic Surgery, University of Wuerzburg Koenig-Ludwig Haus, Brettreichstr. 11, 97074, Wuerzburg, Germany.

Background: The key for successful delivery in minimally-invasive hip replacement lies in the exact knowledge about the surgical anatomy. The minimally-invasive direct anterior approach to the hip joint makes it necessary to clearly identify the tensor fasciae latae muscle in order to enter the Hueter interval without damaging the lateral femoral cutaneous nerve. However, due to the inherently restricted overview in minimally-invasive surgery, this can be difficult even for experienced surgeons.

Methods And Surgical Technique: In this technical note, we demonstrate for the first time how to use the tensor fasciae latae perforator as anatomical landmark to reliably identify the tensor fasciae latae muscle in orthopaedic surgery. Such perforators are used for flaps in plastic surgery as they are constant and can be found at the lateral third of the tensor fasciae latae muscle in a direct line from the anterior superior iliac spine.

Conclusion: As demonstrated in this article, a simple knowledge transfer between surgical disciplines can minimize the complication rate associated with minimally-invasive hip replacement.
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http://dx.doi.org/10.1186/s12891-016-0908-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741054PMC
February 2016

Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance.

Curr Opin Biotechnol 2015 Dec 26;35:127-32. Epub 2015 Jun 26.

Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.
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http://dx.doi.org/10.1016/j.copbio.2015.06.001DOI Listing
December 2015

Sustained regeneration of high-volume adipose tissue for breast reconstruction using computer aided design and biomanufacturing.

Biomaterials 2015 Jun 18;52:551-60. Epub 2015 Mar 18.

Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, 4059 Kelvin Grove, Brisbane, Australia; Institute for Advanced Study, Technical University Munich, Lichtenbergstrasse 2a, 85748 Garching, Munich, Germany. Electronic address:

Adipose tissue engineering offers a promising alternative to the current breast reconstruction options. Here we investigated patient-specific breast scaffolds fabricated from poly(d,l)-lactide polymer with pore sizes>1 mm for their potential in long-term sustained regeneration of high volume adipose tissue. An optimised scaffold geometry was modelled in silico via a laser scanning data set from a patient who underwent breast reconstruction surgery. After the design process scaffolds were fabricated using an additive manufacturing technology termed fused deposition modelling. Breast-shaped scaffolds were seeded with human umbilical cord perivascular cells and cultured under static conditions for 4 weeks and subsequently 2 weeks in a biaxial rotating bioreactor. These in vitro engineered constructs were then seeded with human umbilical vein endothelial cells and implanted subcutaneously into athymic nude rats for 24 weeks. Angiogenesis and adipose tissue formation were observed throughout all constructs at all timepoints. The percentage of adipose tissue compared to overall tissue area increased from 37.17% to 62.30% between week 5 and week 15 (p<0.01), and increased to 81.2% at week 24 (p<0.01), while the seeded endothelial cells self-organised to form a functional capillary network. The presented approach of fabricating customised scaffolds using 3D scans represents a facile approach towards engineering clinically relevant volumes of adipose tissue for breast reconstruction.
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http://dx.doi.org/10.1016/j.biomaterials.2015.01.025DOI Listing
June 2015

Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering.

Stem Cells 2015 Jun;33(6):1696-704

Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia.

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to "make the model organism mouse more human." To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.
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http://dx.doi.org/10.1002/stem.1978DOI Listing
June 2015

A simple technique to seal the medullary canal in cemented revision arthroplasty.

Eur J Orthop Surg Traumatol 2015 Apr 9;25(3):601-2. Epub 2014 Sep 9.

Department of Orthopaedic Surgery, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstr. 11, 97074, Würzburg, Germany,

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http://dx.doi.org/10.1007/s00590-014-1530-0DOI Listing
April 2015

Simulated microgravity affects chondrogenesis and hypertrophy of human mesenchymal stem cells.

Int Orthop 2014 Dec 17;38(12):2615-21. Epub 2014 Jul 17.

Department of Orthopaedic Surgery, Ludwig-Maximilians-University, Campus Großhadern, Marchioninistr. 15, 81377, Munich, Germany,

Purpose: During in vitro chondrogenesis of human mesenchymal stem cells (hMSCs) hypertrophy is an inadvertent event associated with cell differentiation toward the osteogenic lineage. Up to now, there is no stringent experimental control mechanism to prevent hypertrophy of MSCs. Microgravity is known to have an impact on osteogenesis. In this study, the influence of simulated microgravity (SMG) on both chondrogenesis and hypertrophy of hMSCs was evaluated.

Methods: A bioreactor using a rotating wall vessel was constructed to simulate microgravity. Pellet cultures formed from hMSCs (P5) were supplemented with human transforming growth factor-β3 (TGF-β3). The hMSC pellet cultures treated with TGF-β3 were either kept in SMG or in a control system. After three weeks of culture, the chondrogenic differentiation status and level of hypertrophy were examined by safranin-O staining, immunohistochemistry and quantitative real-time PCR.

Results: SMG reduced the staining for safranin-O and collagen type II. The expression of collagen type X α1 chain (COL10A1) and collagen type II α1 chain (COL2A1) were both significantly reduced. There was a higher decrease in COL2A1 than in COL10A1 expression, resulting in a low COL2A1/COL10A1 ratio.

Conclusions: SMG reduced hypertrophy of hMSCs during chondrogenic differentiation. However, the expression of COL2A1 was likewise reduced. Even more, the COL2A1/COL10A1 ratio decreased under SMG conditions. We therefore assume that SMG has a significant impact on the chondrogenic differentiation of hMSCs. However, due to the high COL2A1 suppression under SMG, this culture system does not yet seem to be suitable for a potential application in cartilage repair.
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http://dx.doi.org/10.1007/s00264-014-2454-3DOI Listing
December 2014

Elastofibroma: clinical results after resection of a rare tumor entity.

Orthop Rev (Pavia) 2014 Apr 16;6(2):5329. Epub 2014 Jun 16.

Department of Orthopedics, University Clinic Dusseldorf , Germany.

Elastofibroma (EF) is a benign proliferation of connective tissue and is typically located at the dorsal thoracic wall. Most patients complain about pain during motion in the shoulder girdle. The aim of our study was to evaluate the outcome after surgical treatment of EF. This study provides an overview of typical clinical findings, diagnostics and pathogenesis of this rare entity. In this retrospective study we analyzed data of 12 patients (6 male, 6 female) with EF treated in our institution between 2004 and 2012. The mean follow-up was 4.7 years (range: 5 months to 7.5 years). All tumors were found to be unilateral and all patients had a negative medical history for EF. Visual analogue scale and range of motion (ROM) was documented pre- and postoperatively. In all patients indication for surgical resection was pain or uneasiness during movement. There was no statistically significant difference in ROM of the shoulder between pre- and postoperatively but all patients reported significantly less pain after surgical resection. Patients benefited from tumor resection by a significant reduction of pain levels and improvement of the motion-dependent discomfort.
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http://dx.doi.org/10.4081/or.2014.5329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083310PMC
April 2014

Engineered microenvironments provide new insights into ovarian and prostate cancer progression and drug responses.

Adv Drug Deliv Rev 2014 Dec 23;79-80:193-213. Epub 2014 Jun 23.

Cancer and Molecular Medicine Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, 4059 Brisbane, Australia; Australian Prostate Cancer Research Centre - Queensland, Queensland University of Technology, Translational Research Institute, 37 Kent Street, Woolloongabba, 4102 Brisbane, Australia. Electronic address:

Tissue engineering technologies, which have originally been designed to reconstitute damaged tissue structure and function, can mimic not only tissue regeneration processes but also cancer development and progression. Bioengineered approaches allow cell biologists to develop sophisticated experimentally and physiologically relevant cancer models to recapitulate the complexity of the disease seen in patients. Tissue engineering tools enable three-dimensionality based on the design of biomaterials and scaffolds that re-create the geometry, chemistry, function and signalling milieu of the native tumour microenvironment. Three-dimensional (3D) microenvironments, including cell-derived matrices, biomaterial-based cell culture models and integrated co-cultures with engineered stromal components, are powerful tools to study dynamic processes like proteolytic functions associated with cancer progression, metastasis and resistance to therapeutics. In this review, we discuss how biomimetic strategies can reproduce a humanised niche for human cancer cells, such as peritoneal or bone-like microenvironments, addressing specific aspects of ovarian and prostate cancer progression and therapy response.
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http://dx.doi.org/10.1016/j.addr.2014.06.001DOI Listing
December 2014

Customised osteotomy guides and endoprosthetic reconstruction for periacetabular tumours.

Int Orthop 2014 Jul;38(7):1435-42

Purpose: We sought to analyse clinical and oncological outcomes of patients after guided resection of periacetabular tumours and endoprosthetic reconstruction of the remaining defect.

Methods: From 1988 to 2008, we treated 56 consecutive patients (mean age 52.5 years, 41.1 % women). Patients were followed up either until death or February 2011 (mean follow up 5.5 years, range 0.1-22.5, standard deviation ± 5.3). Kaplan-Meier analysis was used to estimate survival rates.

Results: Disease-specific survival was 59.9 % at five years and 49.7 % at ten and 20 years, respectively. Wide resection margins were achieved in 38 patients, whereas 11 patients underwent marginal and seven intralesional resection. Survival was significantly better in patients with wide or marginal resection than in patients with intralesional resection (p = 0.022). Survival for patients with secondary tumours was significantly worse than for patients with primary tumours (p = 0.003). In 29 patients (51.8 %), at least one reoperation was necessary, resulting in a revision-free survival of 50.5 % at five years, 41.1 % at ten years and 30.6 % at 20 years. Implant survival was 77.0 % at five years, 68.6 % at ten years and 51.8 % at 20 years. A total of 35 patients (62.5 %) experienced one or more complications after surgery. Ten of 56 patients (17.9 %) experienced local recurrence after a mean of 8.9 months. The mean postoperative Musculoskeletal Tumor Society (MSTS) score was 18.1 (60.1 %).

Conclusion: The surgical approach assessed in this study simplifies the process of tumour resection and prosthesis implantation and leads to acceptable clinical and oncological outcomes.
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http://dx.doi.org/10.1007/s00264-014-2314-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071499PMC
July 2014

Hypokalemia mimicking a herniated vertebral disc.

Spine J 2015 Jun 9;15(6):e53-6. Epub 2013 Nov 9.

Department of Orthopaedic Surgery, Campus Großhadern, Ludwig-Maximilians-University, Marchioninistr. 15, D-81377 Munich, Germany.

Background Context: A herniated vertebral disc is a common cause of paralysis. Other causes include infections, tumors, and neurologic diseases. A rare and dangerous but in most cases easily treatable cause is hypokalemia. Clinically, the acute symptoms may resemble a herniated vertebral disc, but hypokalemia per se is life-threatening by causing heart arrest through ventricular tachycardia or fibrillation.

Purpose: A patient with back pain and neurologic deficit in the lower extremities after a history of a herniated vertebral disc presented, who finally receives the diagnosis of hypokalemia.

Study Design: Case report.

Methods: A 25-year-old female patient presenting after a fall with muscle weakness in both legs was followed clinically and radiographically.

Results: Neurological examination showed a lower extremity muscle weakness with three-fifths muscular strength of the quadriceps and tibialis anterior muscle on both sides. Reflexes were diminished bilaterally, anal sphincter tone was normal. Plain radiography suggested a posterior rim fracture of L5, but computed tomography did not confirm this diagnosis. The laboratory investigation revealed a hypokalemia of 1.7 mEq/L. On electrolyte replacement, the patient recovered immediately.

Conclusion: This report describes a misleading diagnostic case of back pain and neurologic deficit after a trauma and sensitizes for the possible life-threatening diagnosis hypokalemia, which is rare but easily treatable.
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http://dx.doi.org/10.1016/j.spinee.2013.08.021DOI Listing
June 2015

The potential role of lycopene for the prevention and therapy of prostate cancer: from molecular mechanisms to clinical evidence.

Int J Mol Sci 2013 Jul 12;14(7):14620-46. Epub 2013 Jul 12.

Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Brisbane, Australia.

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects.
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http://dx.doi.org/10.3390/ijms140714620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742263PMC
July 2013

Surgical resection and radiation therapy of desmoid tumours of the extremities: results of a supra-regional tumour centre.

Int Orthop 2013 Oct 22;37(10):1987-93. Epub 2013 Jun 22.

Department of Orthopedic Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675, Munich, Germany,

Purpose: Desmoid tumours of the extremity have a high recurrence rate. The purpose of this study was to analyse the outcome after resection of these tumours with special emphasis on recurrent disease and adjuvant therapeutic strategies.

Methods: In this retrospective study we evaluated prognostic factors for recurrence-free survival after surgical treatment of desmoid tumours of the extremity in 27 patients with an average age of 41 years treated from 1997 to 2009. Adjuvant radiotherapy (50-60 Gy) was given in five cases with primary and in nine patients with recurrent disease. The average follow-up was 64 months.

Results: The five-year recurrence-free survival in patients with primary disease was 33%. Patients with negative resection margins tended to have a better outcome than patients with positive resection margins, but the difference between both groups was not significant (56 vs 14%, p = 0.145). In patients with positive margins, adjuvant radiotherapy did not significantly improve recurrence-free survival (40 vs 14%, p = 0.523). Patients with local recurrence had a five-year further recurrence-free survival of 47%. In those patients further recurrence-free survival was significantly better after adjuvant radiation (89 vs 25%, p = 0.015). Two thirds of all patients suffered moderate or severe complications due to the treatment regimen.

Conclusions: Compared to desmoids of the trunk or the head and neck region, desmoids affecting the limbs show by far the worst outcome in terms of relapse or treatment-related morbidity. The importance of negative resection margins is still not clear. Particularly in recurrent desmoids adjuvant radiotherapy appears to reduce the further recurrence rate. Therefore, a general use of radiation should be considered for this high-risk group.
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http://dx.doi.org/10.1007/s00264-013-1942-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779554PMC
October 2013

A novel technique to treat Grisel's syndrome: results of a simplified, therapeutical algorithm.

Int Orthop 2013 Jul 9;37(7):1307-13. Epub 2013 May 9.

Department of Orthopedics and Sports Medicine, Technische Universität München, Munich, Germany.

Purpose: Grisel's syndrome is a rare entity and usually develops in paediatric patients after otolaryngologic surgery or infection. It is defined as a fixed torticollis combined with a rotatory atlanto-axial subluxation. The success rate of physiotherapy is low. Conventional therapy concepts imply stage-related recommendations based on the Fielding classification (type I-IV). This classification was introduced in 1977 to assess the degree of subluxation between atlas (C1) and axis (C2). Thus, instability increases from type I to IV. Higher stages may require surgical intervention. The purpose of this study was to evaluate the value of an alternative, less invasive treatment protocol in Grisel's syndrome.

Methods: Irrespective of the underlying Fielding type we treated five children (Fielding type I-III) by manual repositioning under general anaesthesia. Consecutively, the cervical spine was immobilized with a Minerva cast for four to eight weeks. Additional surgical treatment or immobilization in a Halo-Fixateur was not necessary.

Results: Overall period of treatment was reduced, even in patients with delayed diagnosis. No case of recurrence was observed within a follow-up of six months.

Conclusions: Current conventional recommendations suggest invasive treatment with Halo-Fixateur in patients with higher degrees of subluxation (e.g., Fielding type III) or after delayed diagnosis. Even in those patients, this novel therapy concept enables us to achieve excellent clinical results without surgical intervention.
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http://dx.doi.org/10.1007/s00264-013-1895-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685649PMC
July 2013
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