The diagnostic accuracy of 332 incisional biopsies in patients with malignant tumors in the musculoskeletal system.

BACKGROUND: It is known that specimen collection followed by histopathological workup is the core of evidence-based medical therapy of musculoskeletal tumors. There exist many controversies about how a biopsy should be performed. While some centers recommend minimal invasive biopsy procedures, mostly the core needle biopsy (CNB), others prefer the incisional biopsy. PURPOSE OF THE STUDY: This study aimed to determine the accuracy of incisional biopsy for malignant tumors in the musculoskeletal system. Moreover, advantages and disadvantages to other biopsy methods are discussed. METHODS: This retrospective, single-center study about 844 incisional biopsies (benign and malignant) analysis the diagnostic accuracy of 332 malignant tumors, concerning the final histopathological result. In addition, surgical complications are analyzed to find the best way to plan and treat patients timely and correct. Secondary endpoints are the patients age, the pure operation time, as well as the type of tumor, and the subsequent therapy. RESULTS: In summary, incisional biopsy corresponded a sensitivity of 100% for malignancy in 844 incisional biopsies and a specificity of 97.6% in 332 malignant tumors, but it features greater operative expense (incision/suture 23.5 min) and the risk of general anesthesia. CONCLUSION: The method of biopsy should be tailored to the individual patient and the experience of the center performing the procedure.

Diagnostic delay in soft tissue tumors: a single-center study of a university cancer center with a focus on health services research.

BACKGROUND: Lumps and soft tissue tumors (STT) are frequent reasons for consulting a physician. Most STT are benign, and lumps are not always associated with a tumor. MRI is the most advanced imaging modality to assist a provisional diagnosis of STT. Only a small fraction of STT is malignant, these soft tissue sarcomas are known for their aggressive growth. The study aims to analyze the influence of the MRI report on the speed of treatment of patients with suspected STT. METHODS: This was a retrospective, longitudinal, single-center study from 2011-2020. We included adult patients who had biopsies or resections of masses suspicious for STT in MRI exams. MRI reports were classified as benign (I), intermediate/unclear (II), or malignant (III). For these cohorts, time was statistically analyzed from MRI scan to first contact with the University cancer center (UCC) and surgery. Furthermore, distance in kilometers from the patients´ home to the UCC was examined and compared to age and suspected malignancy. RESULTS: Three hundred two patients (♀130; ♂172) were included. Histologic analyses revealed 286 tumors. The average age of the patients was 54.7(SD: 16.2) years. Malignant tumors were more often suspected in older patients (p = 0.0098). Patients with a benign diagnosed tumor in MRI contacted the UCC after an average of 31.3 (SD: 47.8) days. In contrast, patients with suspicion of a malignant tumor contacted the UCC significantly earlier, after 14.1 days (SD: 17.1); p = 0.0098. Likewise, the time between first contact and biopsy/resection was 32.8 days (SD: 35.7) for suspiciously benign tumors, and potentially malignant tumors were treated significantly faster 14.8 (SD: 16.0) days; (p = 0.028). Patients traveled on average 47.5 km (range: 0.5-483) to contact a specialized physician at the UCC. Suspected degree of malignancy or patient´s age had no statistical influence on traveled distance. DISCUSSION: The treatment speed depended to a great extent on the suspected malignancy of the STT in the MRI report. The provisional diagnoses from the radiologist highly influenced the time delay between MRI scan and first contact to the UCC and surgical treatment. No discrimination of age or distance to the UCC was observed in this study.

Can homogeneous, lipomatous tumors be primarily resected without biopsy? A retrospective analysis of 240 tumors.

BACKGROUND: According to guidelines, every soft tissue tumor (STT) larger than 3 cm should be biopsied before definitive resection. Advances in magnetic resonance imaging (MRI) improve the possibility to give a provisional diagnosis of the tumor's entity. Can lipomas and atypical lipomatous tumors (ALTs) of the extremities therefore be primarily marginally resected based on interpretation of MR images without a previous biopsy?. METHODS: In this retrospective, single-center study, 240 patients with the suspicion of a lipomatous tumor in MRI and surgical treatment in our institution between 2011 and 2020 were included. MR imaging was performed before surgery. All resected specimens underwent histopathological analysis. RESULTS: The collective comprised 142 tumors that were suspected as lipoma or ALT by the radiologist and underwent primary marginal resection (PMR). One case had myxoid liposarcoma that was underestimated on MRI and needed radical follow-up resection. One-hundred forty-one patients were cured after PMR. Ninety-eight patients were biopsied initially and in 93 cases resected afterwards according to the necessary oncological margins. CONCLUSION: In our institution, PMR is performed if a lipoma or ALT is suspected on MR imaging. Our treatment method and the diagnostic algorithm are presented. Primary resection spares patients from one surgical procedure, but a slight risk for underestimation of the tumor remains.

Fibrosis and Immune Cell Infiltration Are Separate Events Regulated by Cell-Specific Receptor Notch3 Expression.

BACKGROUND: Kidney injuries that result in chronic inflammation initiate crosstalk between stressed resident cells and infiltrating immune cells. In animal models, whole-body receptor Notch3 deficiency protects from leukocyte infiltration and organ fibrosis. However, the relative contribution of Notch3 expression in tissue versus infiltrating immune cells is unknown. METHODS: Chimeric mice deficient for Notch3 in hematopoietic cells and/or resident tissue cells were generated, and kidney fibrosis and inflammation after unilateral ureteral obstruction (UUO) were analyzed. Adoptive transfer of labeled bone marrow-derived cells validated the results in a murine Leishmania ear infection model. In vitro adhesion assays, integrin activation, and extracellular matrix production were analyzed. RESULTS: Fibrosis follows UUO, but inflammatory cell infiltration mostly depends upon Notch3 expression in hematopoietic cells, which coincides with an enhanced proinflammatory milieu (e.g., CCL2 and CCL5 upregulation). Notch3 expression on CD45+ leukocytes plays a prominent role in efficient cell transmigration. Functionally, leukocyte adhesion and integrin activation are abrogated in the absence of receptor Notch3. Chimeric animal models also reveal that tubulointerstitial fibrosis develops, even in the absence of prominent leukocyte infiltrates after ureteral obstruction. Deleting Notch3 receptors on resident cells blunts kidney fibrosis, ablates NF-κB signaling, and lessens matrix deposition. CONCLUSIONS: Cell-specific receptor Notch3 signaling independently orchestrates leukocyte infiltration and organ fibrosis. Interference with Notch3 signaling may present a novel therapeutic approach in inflammatory as well as fibrotic diseases.

Relevance of Notch Signaling for Bone Metabolism and Regeneration.

Notch1-4 receptors and their signaling pathways are expressed in almost all organ systems and play a pivotal role in cell fate decision by coordinating cell proliferation, differentiation and apoptosis. Differential expression and activation of Notch signaling pathways has been observed in a variety of organs and tissues under physiological and pathological conditions. Bone tissue represents a dynamic system, which is constantly remodeled throughout life. In bone, Notch receptors have been shown to control remodeling and regeneration. Numerous functions have been assigned to Notch receptors and ligands, including osteoblast differentiation and matrix mineralization, osteoclast recruitment and cell fusion and osteoblast/osteoclast progenitor cell proliferation. The expression and function of Notch1-4 in the skeleton are distinct and closely depend on the temporal expression at different differentiation stages. This review addresses the current knowledge on Notch signaling in adult bone with emphasis on metabolism, bone regeneration and degenerative skeletal disorders, as well as congenital disorders associated with mutant Notch genes. Moreover, the crosstalk between Notch signaling and other important pathways involved in bone turnover, including Wnt/ß-catenin, BMP and RANKL/OPG, are outlined.

Correction of Recurrent Equinus Deformity in Surgically Treated Clubfeet by Anterior Distal Tibial Hemiepiphysiodesis.

BACKGROUND: Residual or recurrent equinus deformity is a common problem in surgically treated clubfeet. This deformity may occur due to soft tissue-related reasons or due to bony deformity. An increased anterior distal tibial angle (ADTA) was previously found in 48% of the operated clubfeet. This study aimed to determine the efficacy and safety of anterior distal tibial hemiepiphysiodesis (ADTE) in the treatment of recurrent equinus deformity in patients with an increased ADTA. METHODS: Eighteen children (23 feet) treated by ADTE to correct recurrent equinus deformity in surgically treated clubfeet were included in this retrospective, single-center study. ADTE using 8 plates was performed in children with an increased ADTA (>82 degrees) and inability to dorsiflex the ankle (≤0 degree of dorsiflexion). The mean patient age was 11.3 years (range: 10.2 to 12.9 y). All patients had completed treatment with implant removal after an average of 20.3 months (range: 9 to 37 mo). RESULTS: The mean preoperative ankle dorsiflexion significantly improved from -3.3 degrees (range: -20 to -0 degrees) to 6.1 degrees (range: -15 to 10 degrees) at the time of 8-plate removal (correction rate: 9.4 degrees; P<0.0001). The ADTA was a mean of 87.5 degrees (range: 83 to 110 degrees) before surgery and significantly improved to 75.8 degrees (range: 63 to 106 degrees) at the time of implant removal (correction rate: 11.7 degrees; P<0.0001). Average follow-up was 43.9 months (range: 10 to 76 mo). Follow-up examinations were continued in 11 patients (13 feet) after implant removal. Changes of ankle dorsiflexion (mean: -2.5 degrees) and ADTA (mean: 3.6 degrees) occurred in this group. CONCLUSIONS: ADTE was safe and effective in the treatment of recurrent equinus deformity in surgically treated clubfeet with increased ADTA. Deterioration of ankle dorsiflexion and ADTA occurred after implant removal in some cases. The results of this study have to be analyzed with caution due to the limited number of included patients and its retrospective nature. LEVEL OF EVIDENCE: Level IV-retrospective case series.

Serial casting in early onset scoliosis: syndromic scoliosis is no contraindication.

BACKGROUND: Serial casting is a treatment for early onset scoliosis (EOS) in young children to achieve curve correction before bracing or to postpone initial surgical treatment until the patient is older. Good results have been reported for patients with idiopathic early onset scoliosis (IS). However, there are few reports of results in non-idiopathic cases, and the benefits of non-surgical methods in the syndromic-associated early onset scoliosis subgroup are unknown. METHODS: Retrospective single-institution study of patient charts and X-rays of all cases of sustained serial casting for EOS. Staged correction was obtained by applying three consecutive casts under general anaesthesia. These were changed every 4 weeks, followed by the implementation of a custom-made full-time Chêneau brace. Correction was measured by Cobb angle (CA) and rib-vertebra angle difference (RVAD) on whole spine anterior-posterior radiographs. Statistical analysis was performed via ANOVA. RESULTS: The study group consisted of 6 patiens with IS and 10 with non-idiopathic scoliosis (NIS) - exclusively syndromic-associated. The mean age at onset of treatment was 35 months (±15). The mean follow up was 21 months (±15). In IS patients average CA/RVAD before treatment was 46°(±8)/20°(±12). In NIS patients average CA/RVAD before treatment was 55°(±15)/24°(±14). After application of the third cast, the CA/RVAD was reduced to 20°(±11)/11°(±10) in IS patients. Whereas in NIS patients average CA/RVAD after the thrid cast was 28°(±12)/18°(±13). At latest follow-up the CA/RVAD was 16°(±7)/9°(±8) in IS patients and 31°(±11)/17° (±15) in NIS patients. CONCLUSION: Syndromic etiology is not a contraindication for serial casting in EOS. Our results show a curve correction, measured in CA, of 65% in IS patients and 44% in NIS patients. Significant reduction in the morphologic deformity, measured in RVAD, was achieved in the IS cohort, but not in the NIS cohort. In all cases surgical treatment could be delayed.

Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1.

Tubular cells recruit monocytic cells in inflammatory tubulointerstitial kidney diseases. The cell-cell communication that establishes pro- or anti-inflammatory activities is mainly influenced by cytokines, reactive oxygen species, nitric oxide, and phagocytosis. Key proteins orchestrating these processes such as cold-shock proteins linked with chemoattraction and cell maturation have been identified. The prototypic member of the cold-shock protein family, Y-box binding protein (YB)-1, governs specific phenotypic alterations in monocytic cells and was explored in the present study. Following tubulointerstitial injury by unilateral ureteral obstruction, increased inflammatory cell infiltration and tubular cell CCL5 expression was found in conditional Ybx1 knockout animals with specific depletion in monocytes/macrophages (YB-1ΔLysM). Furthermore, YB-1ΔLysM mice exhibit enhanced tissue damage, myofibroblast activation, and fibrosis. To investigate relevant molecular mechanism(s), we utilized bone marrow-derived macrophage cultures and found that YB-1-deficient macrophages display defects in cell polarization and function, including reduced proliferation and nitric oxide production, loss of phagocytic activity, and failure to upregulate IL-10 and CCL5 expression in response to inflammatory stimuli. Co-culture with primary tubular cells confirmed these findings. Thus, monocytic YB-1 has prominent and distinct roles for cellular feed-forward crosstalk and resolution of inflammatory processes by its ability to regulate cell differentiation and cytokine/chemokine synthesis.

Conservative versus operative treatment of FFP II fractures in a geriatric cohort: a prospective randomized pilot trial.

A clear recommendation regarding treatment strategy of fragility fractures of the pelvic ring is missing. The most typical fracture pattern is a lateral compression type injury with non-displaced fractures of the anterior pubic rami and a unilateral os sacrum fracture (FFP II). We hypothesized that operative treatment would be superior to conservative treatment. From October 2017 to April 2020, a randomized prospective non-blinded trial with n = 39 patients was carried out. Two arms with 17 operative versus 22 conservative cases were created. Inclusion criteria were a posterior pelvic ring fracture FFP type II, age over 60 years and acute fracture (< 3 weeks). Barthel index, pain level (VAS), quality of life (EQ-5D-3L), and Tinetti-Gait Test were determined on admission, at discharge, and after 3, 6, 12 and 24 months. Median follow-up was 12.9 months. The Barthel index (= 0.325), VAS (p = 0.711), quality of life (p = 0.824), and Tinetti-Gait Test (p = 0.913) showed no significant differences between the two groups after 12 months. Two patients switched from the conservative to the operative arm due to persistent immobilization and pain. The one-year mortality rate showed no significant difference (p = 0.175). Our hypothesis that surgical treatment is superior was refuted. No significant benefit was shown in terms of quality of life, mortality and pain levels. The results suggest a more differentiated treatment approach in the future, with initial conservative treatment preferred. A larger multi-center trial is required to confirm these findings.Trial registration: The study was retrospectively registered with the German Clinical Trials Registry (DRKS00013703) on 10/12/2018.

Lipomatous Tumors: A Comparison of MRI-Reported Diagnosis with Histological Diagnosis.

Lipomatous tumors are among the most common soft tissue tumors (STTs). Magnetic resonance imaging (MRI) is a state-of-the-art diagnostic tool used to differentiate and characterize STTs. Radiological misjudgment can lead to incorrect treatment. This was a single-center retrospective study. Two hundred and forty lipomatous tumors were included. MRI diagnoses were categorized as benign, intermediate, or malignant and were compared with histological diagnoses. Tumor volumes were measured by MRI and from surgical specimens. The tumor was correctly categorized 73.3% of the time. A total of 21.7% of tumors were categorized as more malignant in MRI reports than they were by histology, and vice versa for 5.0% of tumors. Volume measured by MRI was not different from actual tumor size in pathology. Atypical lipomatous tumors (ALTs) and liposarcomas (LPSs) were larger when compared with lipomata and occurred in older patients. Based on the MRI-suspected tumor entity, surgical treatment can be planned. Large lipomatous tumors in elderly patients are more likely to be ALTs. However, a safe threshold size or volume for ALTs cannot be determined.

Diagnostic and Therapeutic Pathways of Intramuscular Myxoma.

Intramuscular myxomas (IMMs) are benign tumors. Evidence regarding diagnostic and therapeutic pathways is rare, and guidelines do not exist due to their low incidence. The aim of this study was a retrospective analysis at a university cancer center and the interdisciplinary re-evaluation of the individual diagnostic and therapeutic procedures. Overall, 38 patients were included in the study. IMMs occurred mostly in middle-aged women. At the time of first consultation, 57.9% had few symptoms or were asymptomatic. In 92.1% of the cases, the tumor was localized in the extremities. The lower extremity was affected in 73.7%. The average size of IMMs was 5.0 cm. The proximally located tumors in the gluteus, thighs, and upper arms were significantly larger (p = 0.02) than the distally-located tumors in the forearms and lower legs. An MRI was performed in 97.4%. Based on imaging, an IMM was suspected in 5.6% by radiologists and in 54.1% by musculoskeletal surgeons. An incision biopsy was performed in 68.4% and led in 100.0% to the right histopathological diagnosis. In total, 89.5% of IMMs were resected. Postoperative complications requiring revision occurred in 8.8%. Recurrences or degenerations of IMMs were not reported in any of these cases.

Total Hip Arthroplasty in a Patient with Mucopolysaccharidosis Type IVB.

Introduction. Morquio syndrome or mucopolysaccharidosis (MPS) type IV is a rare autosomal recessive lysosomal storage disease, characterized by abnormal metabolism of glycosaminoglycans associated with specific skeletal deformities, also known as dysostosis multiplex. Case Presentation. We present the case of a 23-year-old patient with advanced osteonecrosis of the femoral head (ONFH) on both sides due to Morquio syndrome. A diagnosis of mucopolysaccharidosis type IVB was made after extensive genetic profiling. The patient had the condition for a long time. At 7 years old, the patient was treated with bilateral pelvic Salter's osteotomy. Afterward, the patient was able to walk freely but could never take part in sports. At 22 years old, pain in the hip increased, and magnetic resonance imaging showed a bilateral femur head necrosis. Hence, the patient underwent cementless total hip arthroplasty (THA). Intraoperatively, a periprosthetic fracture occurred. Therefore, revision surgery with internal fixation was performed on the next day. Postoperatively, a weight-bearing restriction of 20 kg on the left leg was imposed for 6 weeks. The patient made a full recovery and was able to move without residual complaints. Annual orthopedic evaluation in patients treated with surgical intervention is recommended. Discussion. Orthopedic challenges for mucopolysaccharidoses and corresponding bone alterations, known as dysostosis multiplex, involving trunk and limbs with typical radiological findings have been well described. The hip is invariably involved, with dysplasia affecting the femoral neck (coxa valga), femoral epiphysis (loss of sphericity, osteonecrosis), and a flared hypoplastic iliac wing. Symptomatic therapy consists, on the one hand, of a surgical procedure and, on the other hand, a variety of supportive measures. However, the management of joint replacement in lysosomal storage diseases has not been well reported. All patients with MPS should be considered at high risk for surgical intervention requiring anesthesia because of airway and cardiac disease manifestations. In the case of a need for THA, we recommend cemented stem fixation because of the overall poor bone quality in patients with Morquio syndrome.

Osteosynthesis of a Multifragment Femoral Shaft Fracture and Peri-Implant Refracture in an 83-Year-Old Patient with Osteogenesis Imperfecta.

Introduction. Osteogenesis imperfecta (OI) is the term for a heterogenic group of conatal diseases that affect the bone formation. Eight different OI types are known. Patients with types III and IV frequently suffer from fractures without adequate trauma. The literature gives plenty advice for fracture treatment in pediatric OI patients, but there is less for adults, and no recommendations can be found for geriatric OI patients. Case Presentation. We report on an 83-year-old male who suffered from OI type IV. He was able to walk with an individually adapted gait orthosis. In an accident, the patient sustained a distal, multifragment, femoral shaft fracture. The fracture was openly reduced and fixated with a retrograde inserted elastic stable intramedullary nail (ESIN). Three months later, the patient was capable of walking without crutches. Due to another accident, he sustained a peri-implant refracture without failure of the ESIN. We immobilized the leg, and it achieved bony healing without reosteosynthesis. Eleven weeks later, he was again able to mobilize himself with full weight bearing. Discussion. We present a unique case of osteosynthesis in a distal, multifragment, femoral shaft fracture in a geriatric OI patient. No recommendations for the treatment of mature patients with OI can be found in the literature. We present our treatment concept and technique of osteosynthesis with an ESIN. Despite another accident with a peri-implant refracture, sufficient bony healing occurred, which allowed the patient to freely mobilize himself again.

Does eight-plate epiphysiodesis of the proximal tibia in treating angular deformity create intra-articular deformity?

AIMS: Eight-plates are used to correct varus-valgus deformity (VVD) or limb-length discrepancy (LLD) in children and adolescents. It was reported that these implants might create a bony deformity within the knee joint by change of the roof angle (RA) after epiphysiodesis of the proximal tibia following a radiological assessment limited to anteroposterior (AP) radiographs. The aim of this study was to analyze the RA, complemented with lateral knee radiographs, with focus on the tibial slope (TS) and the degree of deformity correction. METHODS: A retrospective, single-centre study was conducted. The treatment group (n = 64 knees in 44 patients) was subclassified according to the implant location in two groups: 1) medial hemiepiphysiodesis; and 2) lateral hemiepiphysiodesis. A third control group consisted of 25 untreated knees. The limb axes and RA were measured on long standing AP leg radiographs. Lateral radiographs of 40 knees were available for TS analysis. The mean age of the patients was 10.6 years (4 to 15) in the treatment group and 8.4 years (4 to 14) in the control group. Implants were removed after a mean 1.2 years (0.5 to 3). RESULTS: No significant differences in RA (p = 0.174) and TS (p = 0.787) were observed. The limb axes were significantly corrected in patients with VVD (p < 0.001). The change in tibial slope (∆TS) did not correlate (r = -0.026; p = 0.885) to the plate's position on the physis when assessed by lateral radiographs. CONCLUSION: We were not able to confirm the reported change in the bony morphology of the proximal tibia on AP radiographs in our patient population. In addition, no significant change in TS was detected on the lateral radiographs. A significant correction of the VVD in the lower limb axes was evident. Position of the implant did not correlate with TS change. Therefore, eight-plate epiphysiodesis is a safe and effective procedure for correcting VVD in children without disturbing the knee joint morphology. Cite this article: Bone Joint J 2020;102-B(10):1412-1418.

Congenital deformation of the posterior arch of the atlas: Subluxation of the atlanto-axial joint with temporary quadriplegia.

Instabilities of the craniocervical junction can be of rheumatic, traumatic, or congenital origin. The reported patient has a congenital malformation of the cervical spine, which is frequently observed in patients with Klippel-Feil syndrome. Her posterior arch of the atlas (C1) is hypoplastic and a chronic subluxation of the atlanto-axial joint would be possible. Although most common fusions in Klippel-Feil syndrome patients exist at C2/3, the majority of studies about Klippel-Feil syndrome deal with pediatric or adolescent individuals. Through extreme flexion of her neck, there was a compression of the spinal cord by the odontoid process. This led to a quadriplegia lasting about 10 min. Over the following weeks, all of her symptoms started to diminish. This situation turned out to be the third episode involving temporary neurological disorders in this 60-year-old female's life.

Delayed onset of a spinal epidural hematoma after facet joint injection.

The treatment of chronic back pain is a challenging problem. Facet joint infiltration is an established treatment for chronic low back pain caused by arthrosis of the lumbar facet joints. Due to the increasing number of patients with chronic low back pain, this therapy has become more frequent. We treated a 51-year-old male patient, who developed an epidural hematoma 2 months after infiltration therapy. Our case shows that even a delayed onset of spinal epidural hematoma is possible and should be kept in mind as a possible cause of acute myelopathy after spinal intervention.

Sources of myofibroblasts in kidney fibrosis: all answers are correct, however to different extent!

Most inflammatory kidney diseases have the final outcome of fibrosis with the loss of kidney architecture and progressive loss of kidney function. Excess matrix deposition is observed, which may be an inadequate attempt to limit organ damage. The primary sources of matrix synthesis are resident cells that may acquire different activated phenotypes and likely orchestrate matrix deposition. Over the last decades, intense efforts were undertaken to define the origin of myofibroblasts, resulting in four different controversially discussed hypotheses: bone marrow recruitment, vascular pericyte-derived myofibroblasts, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT). In a recent article, LeBleu et al. (Nat Med 19(8):1047-1053, 2013) address this issue and come to the conclusion that most of the different hypotheses are likely true, however to different extents. To arrive at this conclusion, the authors have performed genetic cell tracking and quantification by cell labeling in newly generated knockout mouse models. Quantitative analyses have been made and yield the following estimates: 50% of the myofibroblasts are derived through proliferation from resident fibroblasts, 35% differentiate from bone marrow-derived cells, 10% arise from EndMT, and 5% through EMT.