Limb-salvage reconstruction with MUTARS hemipelvic endoprosthesis: A prospective multicenter study

Background

Limb-sparing surgery with hemipelvic megaprosthetic replacement is often limited by the high rate of associated complications. The aim of this evaluation was to assess clinical and oncological findings with respect to type, treatment and outcome of post-operative complications.

Methods

First results of 40 patients treated with individual MUTARS^® hemipelvic endoprostheses were evaluated in a prospective multicenter study.

Results

The mean follow-up period of the 27 male and 13 female patients was 24 months (range 1–61). The diagnosis was, in 29 cases, a primary bone or soft tissue sarcoma, in 11 patients, a metastasis. Clinical evaluation showed a mean Enneking score of 50% (range 10–70%). The oncological outcome revealed 25 patients (62.5%) alive with no evidence of disease. Seventeen of them had a primary tumour, eight a metastatic malignancy. Seven patients (17.5%) had died of their disease and eight (20%) were still alive but had developed a metastases and/or had had a recurrence of the primary tumour. The one- and two-year overall survival rate of the patients was 89% (± 0.10) and 81% (± 0.19), respectively. Post-operative complications occurred in 75% of the patients, predominantly wound-related disorders. The rate of implant revision was 22.5% with three septic and six aseptic cases of implant loosening. The estimated three-year-survival rate of the implant was 61.4% [CI95%: 0.36;0.87].

Conclusions

Periacetabular endoprosthetic replacement showed an acceptable functional and oncological outcome but had a high complication rate owing, predominantly, to infection. The indication for hemipelvic prosthesis in patients with a metastatic disease must be considered seriously.     

Lokalisierte Weichgewebesarkome

best practice onkologie - Weichgewebesarkome sind selten. Die Symptome sind unspezifisch, die Tumoren treten an unterschiedlichsten Lokalisationen auf. Wegen des hohen Verteilungsgrads dieser...     

Total tibia replacement using an allograft (in a patient with adamantinoma). Case report and review of literature

Introduction Adamantinoma is a very rare, low-grade, malignant bone tumour that accounts for approximately 0.4% of all primary bone tumours. Radiographically, adamantinomas vary in length, have a clearly defined outline, with a bubbly appearance and increase the width of the bone. Histologically, epithelial cells, endothelial cells synovial cells have been implicated as cells of origin. Case presentation We present a case of adamantinoma of the tibia, in which a resection of the whole tibia and reconstruction with a total tibia allograft was necessary. Discussion The histological diagnosis is sophisticated. It is often difficult to distinguish an adamantinoma from other tumours. The most frequent described method to treat adamantinoma is wide resection and the use of an allograft. The most common complication is fracture presented similarly in our patient. Conclusion A total tibia allograft as presented in our case is not described in the literature. It fractured due the first year after implantation. Using a prosthesis system instead of the allograft might have saved the limb of our patient.     

Comprehensive analysis of heterotrimeric G-protein complex diversity and their interactions with GPCRs in solution

Agonist binding to G-protein–coupled receptors (GPCRs) triggers signal transduction cascades involving heterotrimeric G proteins as key players. A major obstacle for drug design is the limited knowledge of conformational changes upon agonist binding, the details of interaction with the different G proteins, and the transmission to movements within the G protein. Although a variety of different GPCR/G protein complex structures would be needed, the transient nature of this complex and the intrinsic instability against dissociation make this endeavor very challenging. We have previously evolved GPCR mutants that display higher stability and retain their interaction with G proteins. We aimed at finding all G-protein combinations that preferentially interact with neurotensin receptor 1 (NTR1) and our stabilized mutants. We first systematically analyzed by coimmunoprecipitation the capability of 120 different G-protein combinations consisting of α_i1 or α_sL and all possible βγ-dimers to form a heterotrimeric complex. This analysis revealed a surprisingly unrestricted ability of the G-protein subunits to form heterotrimeric complexes, including βγ-dimers previously thought to be nonexistent, except for combinations containing β₅. A second screen on coupling preference of all G-protein heterotrimers to NTR1 wild type and a stabilized mutant indicated a preference for those Gα_i1βγ combinations containing γ₁ and γ₁₁. Heterotrimeric G proteins, including combinations believed to be nonexistent, were purified, and complexes with the GPCR were prepared. Our results shed new light on the combinatorial diversity of G proteins and their coupling to GPCRs and open new approaches to improve the stability of GPCR/G-protein complexes.G-protein–coupled receptors (GPCRs) are a large class of eukaryotic seven-transmembrane receptors encoded by >800 genes in the human genome. After stimulation by a vast variety of chemically diverse ligands, GPCRs regulate many cellular responses by the activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) (1, 2). The heterotrimeric G-protein complex is assembled from a pool of 16 α-subunits, 5 β-subunits, and 12 γ-subunits (3–5). Extensive analyses of the βγ-dimer formation potential had indicated unrestricted dimer formation for β₁ and β₄ (i.e., dimers with all γ-subunits are found), restricted dimer formation of β₂ and β₃ (e.g., no dimers with γ₁ or γ₁₁), and no or only weak dimer formation for β₅ (6, 7). Although a comprehensive analysis of Gαβγ complex formation is missing, it is likely that most of the Gαβγ combinations are capable of forming a functional complex (8–10). Taking into account the βγ-dimers believed to be nonexistent, this restriction still results in a number of ∼700 potential Gαβγ combinations.The enormous number of potential interactions between the >800 GPCRs and several hundred G-protein combinations quickly raised the question of how the interaction between GPCR and G protein is determined. Besides tissue-specific expression (4), it has quickly become clear that GPCRs display specificity for G-protein coupling and biased agonism (9, 11, 12). Although a variety of structures have been solved for G proteins and, more recently, for GPCRs (13–15), the only structural snapshot of the interaction between a GPCR and a G protein is provided by the structure of the complex between β₂ adrenergic receptor and Gα_sSβ₁γ₂ (16). This structure reveals—as many previous studies had suggested—that the α-subunit is the main interaction partner of the GPCR. Nevertheless, how the GPCR discriminates between the different α-subunits and how the βγ-dimer influences this interaction has not been definitively answered yet. To this end, additional structures of GPCR/G-protein complexes are needed that could shed more light on these questions. However, the crystallization of GPCR/G-protein complexes poses a big challenge because, on the one hand, GPCRs tend to show low expression levels and low stability in detergent (17), and, on the other hand, the Gα protein gains flexibility in complex with a GPCR (16, 18–20).In the past years, we developed strategies based on directed evolution to generate GPCRs that not only exhibit higher expression levels, but also higher stability in detergents (21–24). Recently, these efforts have led to the determination of several structures of evolved mutants of neurotensin receptor 1 (NTR1), which were solved from crystals obtained by vapor diffusion in short-chain detergents (25). Many of the evolved NTR1 mutants, besides displaying better expression and better stability, still showed functional coupling to G proteins (23, 25). Signaling is especially improved if one of the persistently selected mutations that increases stability—replacing wild-type (WT) arginine at position 167 by leucine—is reversed to the WT amino acid arginine. This result is unsurprising, because this arginine is part of the signaling-relevant E/DR¹⁶⁷Y motif (21, 23).With optimized GPCRs at hand, we set out to find those G-protein combinations that show the most efficient interaction with our NTR1 mutants. For this purpose, we screened the natural pool of G proteins composed of α_i1- or α_sL-subunits and all possible βγ-dimers for their formation of a heterotrimeric G-protein complex and their interaction with solubilized NTR1 mutants in detergent.Here, we present the results of, to our knowledge, the first comprehensive analysis of heterotrimeric G-protein complex diversity and GPCR interactions. This analysis reveals that combinations like α_i1β₂γ₁, which were previously believed to be nonexistent (6), indeed exist and can be purified. Moreover, those newly identified combinations are among the combinations that performed best in forming a complex between NTR1 and heterotrimeric G protein. We also present data indicating that GPCR mutants, which exhibit modest functional coupling with G protein, still form a GPCR/G-protein complex and may be stabilizing this complex. Our study suggests that the combination of stable GPCR mutants and carefully selected G-protein combinations may be a promising way of stabilizing this intrinsically dynamic signaling complex for detailed structural and functional studies.     

Overlooked osteosarcoma in a patient undergoing total knee arthroplasty. A case report

A 72-year-old woman presented with pain, swelling, and decreased range of motion of the left knee joint after total knee arthroplasty in 2005. We performed standard x-rays, which were highly suspicious for an osteosarcoma of the distal femur; this was proven by open biopsy. Retrospectively, the x-rays taken before implantation of the prosthesis showed suspicious findings. Because the femur was tumor-contaminated, with the intramedullary adjustment far-reaching proximally, a limb salvage procedure was no longer possible. To improve function, we decided to perform a stump-lengthening procedure using a special implant. With regard to the dismal consequences, we recommend that every suspicious finding before an elective surgical procedure be examined with further diagnostics and, if necessary, histological confirmation.     

Grade I chondrosarcoma of bone: the Münster experience

The surgical treatment of low-grade chondrosarcoma is controversial and the clinical course is difficult to predict. The purpose of this retrospective study was to review the authors’ experience with the surgical treatment of 80 patients with grade I chondrosarcoma. Intralesional resection margins increased the rate of local recurrence statistically significant (p < 0.001). However, there was no influence of the resection margins on the overall survival (p > 0.05) or on the rate of metastasis (p > 0.05). Conservative surgery for special indications with adjuvant use of PMMA (poly-methylmethacrylate) offers satisfying local tumour control rates in the long bones. However, after intralesional tumour resection of pelvic chondrosarcoma, four out of four patients developed a local recurrence, whereas no patient treated with wide resection margins received a local relapse, which has been statistically significant (p < 0.001). In conclusion, intralesional resection of a grade I chondrosarcoma has a higher overall risk of local recurrence but is not associated with a poorer survival. This procedure can be recommended for stage I A tumours of the long bones of the extremities. However, in pelvic lesions it should be avoided because of a 100% recurrence rate.     

Cartilage tumours of the bone. Diagnosis and therapy

Primary malignant bone tumours are rare. The annual incidence of these tumours is 10 per 1 million. Nearly 30% of the primary malignant bone tumours are malignant cartilage tumours. The frequency of benign cartilage tumours cannot be definitely estimated because these tumours are normally clinically inapparent and therefore often diagnosed as an incidental finding. The cartilage tumours appear as benign lesions (e.g. chondroma), as borderline tumours (proliferative chondroma vs grade I chondrosarcoma) or as highly malignant chondrosarcoma (e.g. dedifferentiated chondrosarcoma). Commensurate with the different clinical and oncological manifestations of the cartilage tumours, there are wide differences in the treatment and clinical course of the individual tumour. This article discusses the problems in the diagnosis and treatment of cartilage tumours from an orthopaedic point of view.     

Proximaler Humerusersatz bei malignen Schultergelenktumoren

OBJECTIVE: The aim of the operation is local tumor control in malignant primary and secondary bone tumors of the proximal humerus. Limb salvage and preservation of function with the ability to lift the hand to the mouth. Stable suspension of the arm in the shoulder joint or the artificial joint. INDICATIONS: Primary malignant bone tumors of the proximal humerus or the scapula with joint infiltration but without involvement of the vessel/nerve bundle. Metastases of solid tumors with osteolytic defects in palliative or curative intention or after failure of primary osteosynthesis. CONTRAINDICATIONS: Tumor infiltration of the vessel/nerve bundle. Massive tumor infiltration of the soft tissues without the possibility of sufficient soft tissue coverage of the implant. SURGICAL TECHNIQUE: Transdeltoid approach with splitting of the deltoid muscle. Preparation and removal of the tumor-bearing humerus with exposure of the vessel/nerve bundle. Ensure an oncologically sufficient soft tissue and bone margin in all directions of the resection. Cementless or cemented stem implantation. Reconstruction of the joint capsule and fixation of the prosthesis using a synthetic tube. Soft tissue coverage of the prosthesis with anatomical positioning of the muscle to regain function. POSTOPERATIVE TREATMENT: Immobilization of the arm/shoulder joint for 4-6?weeks in a Gilchrist bandage. Passive mobilization of the elbow joint after 3-4?weeks. Active mobilization of the shoulder and elbow joint at the earliest after 4-6?weeks.