Characteristics and patient-reported outcomes of long-term cancer survivors after apatinib-based therapy: an online survey.

BACKGROUND: Data on long-term cancer survivors treated with apatinib are lacking. This study aimed to describe the characteristics of long-term cancer survivors after apatinib-based therapy, and to know about their satisfaction degree with apatinib and severity of depression and insomnia. METHODS: Patients with solid tumors who had received apatinib-based therapy for at least 5 years were invited to complete an online questionnaire. Characteristics of patients and treatment, knowledge of apatinib, satisfaction degree, and severity of depression and insomnia assessed by Patient Health Questionnaire-9 and Insomnia Severity Index were collected. RESULTS: Between December 8, 2023 and March 1, 2024, a total of 436 patients completed the online questionnaire. Most patients were satisfied with the efficacy (96.6%) and safety (93.1%) of apatinib, were willing to continue apatinib treatment (99.5%), and would recommend apatinib to other patients (93.3%). Continuous apatinib treatment resulted in significant negative impact on daily life, work, or study in only two (0.5%) patients. Almost all patients currently had no or mild depression (97.0%) and insomnia (97.9%) problems. The most common patient-reported adverse events were hand-foot syndrome (21.3%) and hypertension (18.3%). CONCLUSIONS: Our survey showed a high satisfaction degree with apatinib in long-term cancer survivors. Long-term apatinib treatment resulted in almost no negative impact on patient's quality of life.

Is 3D-printed self-stabilizing endoprosthesis reconstruction without supplemental fixation following total sacrectomy a viable approach for sacral tumours?

PURPOSE: The spinopelvic reconstruction poses significant challenges following total sacrectomy in patients with malignant or aggressive benign bone tumours encompassing the entire sacrum. In this study, we aim to assess the functional outcomes and complications of an integrated 3D-printed sacral endoprostheses featuring a self-stabilizing design, eliminating the requirement for supplemental fixation. METHODS: We retrospectively analyzed patients with sacral tumours who underwent total sacrectomy followed by reconstruction with 3D-printed self-stabilizing endoprosthesis. Clinically, we evaluated functional outcomes using the 1993 version of the musculoskeletal tumour society (MSTS-93) score. Perioperative and postoperative complications were also documented. RESULTS: 10 patients met final inclusion criteria. The median age was 49 years (range, 31-64 years). The median follow-up time was 26.5 months (range, 15-47 months). Median postoperative functional MSTS-93 was 22.5 (range, 13-25). The median operation time was 399.5 min (305-576 min), and the median intraoperative blood loss was and 3200 ml (2400-7800 ml). Complications include wound dehiscence in one patient, bowel, bladder, and sexual dysfunction in four patients, cerebrospinal fluid leak in one patient, and tumour recurrence in one patient. There were no mechanical complications related to the endoprosthesis at the last follow-up. CONCLUSION: The utilization of 3D-printed self-stabilizing endoprosthesis proved to be a viable approach, yielding satisfactory short-term outcomes in patients undergoing total sacral reconstruction without supplemental fixation.

3D-Printed custom-made hemipelvic endoprosthetic reconstruction following periacetabular tumor resection: utilizing a novel classification system.

BACKGROUND: Customized 3D-printed pelvic implants with a porous structure have revolutionized periacetabular pelvic defect reconstruction after tumor resection, offering improved osteointegration, long-term stability, and anatomical fit. However, the lack of an established classification system hampers implementation and progress. METHODS: We formulated a novel classification system based on pelvic defect morphology and 3D-printed hemipelvis endoprostheses. It integrates surgical approach, osteotomy guide plate and prosthesis design, postoperative rehabilitation plans, and perioperative processes. RESULTS: Retrospectively analyzing 60 patients (31 males, 29 females), we classified them into Type A (15 patients: Aa = 6, Ab = 9), Type B (27 patients: Ba = 15, Bb = 12), Type C (17 patients). All underwent customized osteotomy guide plate-assisted tumor resection and 3D-printed hemipelvic endoprosthesis reconstruction. Follow-up duration was median 36.5 ± 15.0 months (range, 6 to 74 months). The mean operating time was 430.0 ± 106.7 min, intraoperative blood loss 2018.3 ± 1305.6 ml, transfusion volume 2510.0 ± 1778.1 ml. Complications occurred in 13 patients (21.7%), including poor wound healing (10.0%), deep prosthesis infection (6.7%), hip dislocation (3.3%), screw fracture (1.7%), and interface loosening (1.7%). VAS score improved from 5.5 ± 1.4 to 1.7 ± 1.3, MSTS-93 score from 14.8 ± 2.5 to 23.0 ± 5.6. Implant osseointegration success rate was 98.5% (128/130), with one Type Ba patient experiencing distal prosthesis loosening. CONCLUSION: The West China classification may supplement the Enneking and Dunham classification, enhancing interdisciplinary communication and surgical outcomes. However, further validation and wider adoption are required to confirm clinical effectiveness.

Reconstruction of the proximal radius with 3D-printed personalized prosthesis after tumor resection: case series.

BACKGROUND: Giant cell tumor of bone (GCTB) (Campanacci III) or malignant tumors extend to the epiphyseal region of the proximal radius, and intra-articular resection of the proximal radius is often needed. In the present study, we present the patients who underwent reconstruction of the proximal radius with 3D-printed personalized prosthesis after tumor resection, aiming to describe the prosthesis design and surgical technique and evaluate the clinical outcomes of this method. METHODS: Between November 2018 and January 2021, 9 patients received radial hemiarthroplasty with 3D-printed personalized prostheses after tumor resection. The pathologic diagnosis was GCTB (Campanacci III) in 7 patients, osteosarcoma (IIB) in 1 patient, and synovial sarcoma (IIB) in 1 patient. The range of motion (ROM) and strength in terms of elbow flexion/extension and forearm supination/pronation were evaluated. Pain was assessed by the visual analog scale (VAS) preoperatively and at each follow-up visit. To evaluate the functional outcome, the Mayo Elbow Performance Score (MEPS) system and the Musculoskeletal Tumor Society (MSTS) scoring system were administered at each follow-up visit. Complications and oncological outcomes were recorded. RESULTS: The patients were followed from 24 to 51 months, with a median follow-up of 35 months. No patients were lost to follow-up. During the follow-up, local recurrence and metastasis were not observed. The VAS score improved from a median of 5 points (range 4-7) preoperatively to 1 point (range 0-2) at the last follow-up visit. The mean MEPS score was 88.5% (83-93), and the mean MSTS score was 25.3 (24-27) at the last follow-up visit. No complications such as infection and aseptic loosening were detected. CONCLUSIONS: The implantation of a 3D-printed personalized prosthesis after proximal radial resection showed excellent oncologic outcomes and postoperative function at short-term follow-up and is a viable alternative method for reconstruction of the proximal radius bone defect after tumor resection.

Advanced Pelvic Girdle Reconstruction with three dimensional-printed Custom Hemipelvic Endoprostheses following Pelvic Tumour Resection.

PURPOSE: Resection of pelvic bone tumours and subsequent pelvic girdle reconstruction pose formidable challenges due to the intricate anatomy, weight-bearing demands, and significant defects. 3D-printed implants have improved pelvic girdle reconstruction by enabling precise resections with customized guides, offering tailored solutions for diverse bone defect morphology, and integrating porous surface structures to promote osseointegration. Our study aims to evaluate the long-term efficacy and feasibility of 3D-printed hemipelvic reconstruction following resection of malignant pelvic tumours. METHODS: A retrospective review was conducted on 96 patients with primary pelvic malignancies who underwent pelvic girdle reconstruction using 3D-printed custom hemipelvic endoprostheses between January 2017 and May 2022. Follow-up duration was median 48.1 ± 17.9 months (range, 6 to 76 months). Demographic data, imaging examinations, surgical outcomes, and oncological evaluations were extracted and analyzed. The primary endpoints included oncological outcomes and functional status assessed by the Musculoskeletal Tumor Society (MSTS-93) score. Secondary endpoints comprised surgical duration, intraoperative bleeding, pain control and complications. RESULTS: In 96 patients, 70 patients (72.9%) remained disease-free, 15 (15.6%) had local recurrence, and 11 (11.4%) succumbed to metastatic disease. Postoperatively, function improved with MSTS-93 score increasing from 12.2 ± 2.0 to 23.8 ± 3.8. The mean operating time was 275.1 ± 94.0 min, and the mean intraoperative blood loss was 1896.9 ± 801.1 ml. Pain was well-managed, resulting in substantial improvements in VAS score (5.3 ± 1.8 to 1.4 ± 1.1). Complications occurred in 13 patients (13.5%), including poor wound healing (6.3%), deep prosthesis infection (4.2%), hip dislocation (2.1%), screw fracture (1.0%), and interface loosening (1.0%). Additionally, all patients achieved precise implantation of customized prosthetics according to preoperative plans. T-SMART revealed excellent integration at the prosthesis-bone interface for all patients. CONCLUSION: The use of a 3D-printed custom hemipelvic endoprosthesis, characterized by anatomically designed contours and a porous biomimetic surface structure, offers a potential option for pelvic girdle reconstruction following internal hemipelvectomy in primary pelvic tumor treatment. Initial results demonstrate stable fixation and satisfactory mid-term functional and radiographic outcomes.

Advancements in Photothermal Therapy Using Near-Infrared Light for Bone Tumors.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

Pelvic-girdle reconstruction with three-dimensional-printed endoprostheses after limb-salvage surgery for pelvic sarcomas: current landscape.

Resection of pelvic bone tumors and the subsequent reconstruction of the pelvic girdle pose challenges due to complex anatomy, load-bearing demands, and significant defects. 3D-printed implants have revolutionized pelvic girdle reconstruction by offering customized solutions, porous surface structures for precise resection with custom guides, and improved integration. Many tertiary medical centers have adopted 3Dprinted hemipelvic endoprostheses, leading to enhanced outcomes. However, most studies are limited to single centers, with a small number of cases and short follow-up periods. Additionally, the design of these implants often relies heavily on individual experience, resulting in a lack of uniformity and significant variation. To provide a comprehensive assessment of this technology, we conducted an analysis of existing literature, encompassing tumor resection classification, various types of prosthesis design, reconstruction concepts, and post-reconstruction functional outcomes.

The optimal strategy for 3D-printed uncemented endoprosthesis for the bone defect reconstruction of the distal radius, based on biomechanical analysis and retrospective cohort study.

INTRODUCTION: Prosthetic reconstruction after resecting giant cell tumor of bone (GCTB) of the distal radius has been proposed. However, this is generally associated with various complications. To improve the functional outcomes, we designed a three-dimensional (3D)-printed uncemented endoprosthesis. Meanwhile, using finite-element analysis and clinical observation, an optimization strategy was explored. MATERIALS AND METHODS: We retrospectively analyzed patients with Campanacci III or recurrent GCTB of the distal radius who underwent 3D-printed uncemented endoprosthesis reconstruction. Clinically, according to the different palmar tilts of the endoprosthesis, patients were divided into the biological angle (BA) group and the zero-degree (ZD) group. We recorded and evaluated the differences in functional outcomes and complications between the two groups. Biomechanically, four 3D finite-element models (normal and customized endoprostheses with three different implemented palmar tilts) were developed. RESULTS: We analyzed 22 patients (12 males and 10 females). The median follow-up period was 60 (range, 19-82) months. Of the 22 patients, 11 patients were included in the BA group and the remaining 11 patients were in the ZD group. Both groups showed no significant differences in the range of motion, Mayo score, and disabilities of the arm, shoulder, and hand scores postoperatively. The subluxation rate was significantly lower in the ZD group than in the BA group. The biomechanical results showed similar stress and displacement distribution patterns in the normal and prosthetic reconstruction models. Additionally, the endoprosthesis with 0° palmar tilt showed better biomechanical performance. CONCLUSION: 3D-printed uncemented endoprosthesis provides acceptable midterm outcomes in patients undergoing distal radius reconstruction. Optimizing the design by decreasing the palmar tilt may be beneficial for decreasing the risk of wrist joint subluxation.

Three-Dimensional Multimodality Image Reconstruction as Teaching Tool for Case-based learning among medical postgraduates: a focus on primary pelvic bone Tumour Education.

BACKGROUND: Postgraduate medical education in oncology orthopedics confronts obstacles when instructing on pelvic tumors, primarily due to their intricate anatomy and the limitations of conventional teaching techniques. The employment of Three-dimensional multimodality imaging (3DMMI) can be considered a valuable teaching tool, as it gracefully elucidates the intricacies of pelvic anatomical structures and the interactions between tumors and surrounding tissues through three-dimensional imaging, thereby providing a comprehensive and nuanced perspective. This study aimed to assess the feasibility and effectiveness of incorporating 3DMMI in combination with a Case-Based Learning (CBL) approach for postgraduate education. METHODS: The study encompassed a 10-week course involving 90 surgical postgraduates, focusing on common pelvic tumor diseases. Students were assigned representative clinical cases, and each group created a PowerPoint presentation based on these cases. The core educational content included fundamental knowledge of pelvic anatomy, as well as clinical presentations, radiological features, and treatment principles of common pelvic tumor diseases. The research compared two groups: a traditional CBL group (n = 45) and a 3DMMI-CBL group (n = 45). The 3DMMI-CBL group had access to advanced imaging technology for better visualization. Various evaluations, including image interpretation, theoretical knowledge, and questionnaires, were used to assess the learning outcomes. RESULTS: The 3DMMI-CBL group outperformed the CBL group not only in the imaging diagnosis of common pelvic diseases but also in their mastery of the related theoretical knowledge. Student questionnaires indicated higher scores for the 3DMMI-CBL group in basic pelvic anatomy knowledge (8.08 vs. 6.62, p < 0.01), image interpretation (8.15 vs. 6.69, p < 0.01), learning efficiency (8.07 vs. 7.00, p < 0.01), clinical reasoning (7.57 vs. 6.77, p < 0.01), and learning interest (8.46 vs. 7.00, p < 0.01). Teacher questionnaires revealed that 3DMMI technology enhanced teachers' clinical knowledge, facilitated instruction, and increased overall satisfaction and interest in teaching. CONCLUSION: Our study introduced an enhancement to the conventional Case-Based Learning (CBL) model by incorporating 3DMMI technology for visualizing pelvic anatomy. In contrast to pure CBL, this adaptation improved teacher instruction, substantially heightened student engagement, ignited greater interest in learning, and boosted overall efficiency, ultimately leading to positive learning outcomes. Consequently, our study demonstrated the potential feasibility and acceptability of the 3DMMI-CBL teaching method for postgraduates in pelvic bone tumor education.

Is three-dimension-printed mesh scaffold an alternative to reconstruct cavity bone defects near joints?

PURPOSE: Reconstruction of cavity bone defects after curettage of benign bone tumours around the joint remains challenging. We designed a novel 3D-printed mesh scaffold as a substitute for bone cement, aiming to support the articular surface, protect the subchondral bone, and reduce complication rates. METHODS: We retrospectively analyzed seven patients who received curettage and reconstruction using a 3D-printed mesh scaffold between January 2020 and June 2021. Pain and function were evaluated using the 10-cm Visual Analogue Scale (VAS) score and the 1993 version of the Musculoskeletal Tumor Society (MSTS-93) score. Radiographs were used to evaluate articular surface supporting, subchondral bone protection, and complications. RESULTS: The median functional MSTS-93 and VAS scores were both improved after surgery, and the median 3D-printed mesh scaffold volume was smaller than the median defect volume. Articular surface supporting, subchondral bone preservation, and osteogenesis were observed post-operatively. No related complications were observed during the last follow-up. CONCLUSIONS: The 3D-printed mesh scaffold provided sufficient mechanical support for the articular surface and protected the subchondral bone. We recommended the 3D-printed mesh structure as an alternative to repair cavity bone defects around joints.

Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications.

The current diagnosis and treatment of sarcoma continue to show limited timeliness and efficacy. In order to enable the early detection and management of sarcoma, increasing attentions have been given to the tumor microenvironment (TME). TME is a dynamic network composed of multiple cells, extracellular matrix, vasculature, and exosomes. Exosomes are nano-sized extracellular vesicles derived from various cells in the TME. The major function of exosomes is to promote cancer progress and metastasis through mediating bidirectional cellular communications between sarcoma cells and TME cells. Due to the content specificity, cell tropism, and bioavailability, exosomes have been regarded as promising diagnostic and prognostic biomarkers, and therapeutic vehicles for sarcoma. This review summarizes recent studies on the roles of exosomes in TME of sarcoma, and explores the emerging clinical applications.

Synchronous lung and multiple soft tissue metastases developed from osteosarcoma of tibia: a rare case report and genetic profile analysis.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor with a highly metastatic propensity in children and young adolescents. The majority of metastases develope in the lung, while metastases to the extrapulmonary locations have rarely been discussed, especially in skeletal muscle. CASE PRESENTATION: We reported a young patient with pathologically diagnosed osteosarcoma of the right tibia who was initially treated with standard chemotherapy and complete surgical resection. However, pulmonary metastases and multiple soft tissue masses in skeletal muscle developed four years after the index surgical resection. Subsequently, a targeted next-generation sequencing assay based on an 806 oncogenes and tumor suppressor genes panel was performed to analyze genetic alterations in this patient with rare metastatic pattern. The genetic analysis revealed canonical somatic mutations of RB1 and germline variants of ALK (c.862 T > C), BLM (c.1021C > T), PTCH1 (c.152_154del), MSH2 (c.14C > A), RAD51C (c.635G > A). Using silico prediction programs, the germline variants of the MSH2 and RAD51C were predicted as "Possibly Damaging" by Polymorphism Phenotyping v2 (PolyPhen-2) and "Tolerated" by Sorting Intolerant from Tolerant (SIFT); BLM was classified as "Tolerated", while the germline variant of ALK was predicted to be pathogenic by both PolyPhen-2 and SIFT. CONCLUSIONS: Osteosarcoma with extrapulmonary metastases is rare, especially located in the skeletal muscle, which predicts a worse clinical outcome compared with lung-only metastases. The several novel variants of ALK, BLM, PTCH1 in this patient might expand the mutational spectrums of the osteosarcoma. All the results may contribute to a better understanding of the clinical course and genetic characteristics of osteosarcoma patients with metastasis.

Hip reconstruction using a customized intercalary prosthesis with the rhino horn-designed uncemented stem for ultrashort proximal femur segments following tumor resection: a combined biomechanical and clinical study.

BACKGROUND: Hip-preserved reconstruction for patients with ultrashort proximal femur segments following extensive femoral diaphyseal tumor resection is a formidable undertaking. A customized intercalary prosthesis with a rhino horn-designed uncemented stem was developed for the reconstruction of these extensive skeletal defects. METHODS: This study was designed to analyze and compare the differences in the biomechanical behavior between the normal femur and the femur with diaphyseal defects reconstructed by an intercalary prosthesis with different stems. The biomechanical behavior under physiological loading conditions is analyzed using the healthy femur as the reference. Five three-dimensional finite element models (healthy, customized intercalary prosthesis with four different stems implemented, respectively) were developed, together with a clinical follow-up of 12 patients who underwent intercalary femoral replacement. RESULTS: The biomechanical results showed that normal-like stress and displacement distribution patterns were observed in the remaining proximal femur segments after reconstructions with the rhino horn-designed uncemented stems, compared with the straight stem. Stem A showed better biomechanical performance, whereas the fixation system with Stem B was relatively unstable. The clinical results were consistent with the FEA results. After a mean follow-up period of 32.33 ± 9.12 months, osteointegration and satisfactory clinical outcomes were observed in all patients. Aseptic loosening (asymptomatic) occurred in one patient reconstructed by Stem B; there were no other postoperative complications in the remaining 11 patients. CONCLUSION: The rhino horn-designed uncemented stem is outstanding in precise shape matching and osseointegration. This novel prosthesis design may be beneficial in decreasing the risk of mechanical failure and aseptic loosening, especially when Stem A is used. Therefore, the customized intercalary prosthesis with this rhino horn-designed uncemented stem might be a reasonable alternative for the reconstruction of SSPF following extensive tumor resection.

Cementless curved endoprosthesis stem for distal femoral reconstruction in a Chinese population: a combined anatomical & biomechanical study.

BACKGROUND: The endoprosthetic knee reconstruction using a current universal femoral stem might not be suitable for local population due to the anatomical difference between Chinese and Western populations. We measured the anatomical parameters of Chinese femurs as reference for stem design, and proposed a cementless, curved, short endoprosthesis stem for the reconstruction of distal femur. This study analyzed the biomechanical performance of the newly designed stem aimed at the identification of better operative strategy. METHODS: The CT-scanning data of femurs derived from 96 healthy Chinese volunteers were imported into the Mimics software, and a segmental measurement strategy was applied to evaluate the radius of curvature (ROC) of the femoral medullary cavity. Then, 4 kinds of endoprosthetic replacement models were created based on the measurement results. Model A: the distal tumor resected femora + straight stem A; Model B: the distal tumor resected femora + curved stem B; Model C: the distal tumor resected femora + curved stem C; Model D: the distal tumor resected femora + curved stem D. Finally, the mechanical difference among these models were compared by finite element analysis. RESULTS: The mean femoral ROC of Segment1, 2, 3, 4, 5 measured in the present study was 724.5 mm, 747.5 mm, 1016.5 mm, 1286.5 mm, and 1128 mm, respectively. Based on the femoral ROC of Segment2, the stem ROC of the curved stem B, C, and D was designed as 475 mm, 700 mm, and 1300 mm, respectively. Generally, all endoprosthetic replacement models showed a normal-like stress distribution on the femurs. However, compared to the straight stem, the biomimetic curved stem showed better biomechanical performance both in terms of reducing the extent of the stress shielding of the femur and in terms of minimizing the stress distribution of the implant. CONCLUSIONS: The uncemented, curved, short stem with suitable ROC can perfectly match the Chinese femoral canal morphology which has better mechanical properties than the conventional femoral stem. Thus, this newly designed femoral stem might be an optimized method for treatment of malignant femoral tumours in the Chinese populations in the case that the numerical results are supported by future experimental studies.

Three-dimensional printed customized uncemented unipolar prosthesis combined with ligament reconstruction for tumorous defect of the distal femur in children.

BACKGROUND: Hemiarthroplasty following tumor resection of the distal femur in children provides a chance to preserve the proximal tibial physis for limb elongation. Based on three-dimensional (3D) printing technology, the uncemented unipolar prosthesis with joint stability reinforced structures (JSRSs) was custom-designed for our cases. This study aimed to describe the design and assess the short-term outcomes of this refined prosthetic hemiarthroplasty. METHODS: Seven patients (four females and three males) received 3D-printed customized uncemented unipolar prosthesis for hemiarthroplasty after removal of the distal femur, from September 2019 to October 2020 at our Orthopedics department. The limb function, growth of the preserved proximal tibial physis, joint stability, and limb length discrepancy (LLD) were assessed. Complications were recorded. RESULTS: Six patients survived with no evidence of metastasis or local recurrence at the last follow-up, and one patient died of lung metastasis at 19 months postoperatively. Follow-up ranged from 19 to 32 months, with an average of 26 months. Elongation of the tibia was observed in all cases. At the last follow-up, four patients exhibited equal growth length compared with the healthy contralateral tibia. LLD ranged from 0.8 to 1.6 cm with a mean of 1.3 cm. The average knee range of motion was 95.3° of flexion and 4.5° of extension. All patients achieved satisfactory postoperative limb function with a mean MSTS score of 25.8. The results of the drawer, Lachman, and pivot shift tests were negative in all patients. During follow-up, painless joint space narrowing was observed in two patients. The screw for ligament fixation loosened in one of the seven patients at 17 months postoperatively. No subluxation of the joint, angular deformity, or breakage of the implant was detected in the remaining patients. CONCLUSIONS: 3D-printed customized uncemented unipolar prosthesis with JSRS would be a good choice for reconstructing tumorous defect in the distal femur in children.

Targeting Myeloid-Derived Suppressor Cells for Premetastatic Niche Disruption After Tumor Resection.

Surgical resection is a common therapeutic option for primary solid tumors. However, high cancer recurrence and metastatic rates after resection are the main cause of cancer related mortalities. This implies the existence of a "fertile soil" following surgery that facilitates colonization by circulating cancer cells. Myeloid-derived suppressor cells (MDSCs) are essential for premetastatic niche formation, and may persist in distant organs for up to 2 weeks after surgery. These postsurgical persistent lung MDSCs exhibit stronger immunosuppression compared with presurgical MDSCs, suggesting that surgery enhances MDSC function. Surgical stress and trauma trigger the secretion of systemic inflammatory cytokines, which enhance MDSC mobilization and proliferation. Additionally, damage associated molecular patterns (DAMPs) directly activate MDSCs through pattern recognition receptor-mediated signals. Surgery also increases vascular permeability, induces an increase in lysyl oxidase and extracellular matrix remodeling in lungs, that enhances MDSC mobilization. Postsurgical therapies that inhibit the induction of premetastatic niches by MDSCs promote the long-term survival of patients. Cyclooxygenase-2 inhibitors and ß-blockade, or their combination, may minimize the impact of surgical stress on MDSCs. Anti-DAMPs and associated inflammatory signaling inhibitors also are potential therapies. Existing therapies under tumor-bearing conditions, such as MDSCs depletion with low-dose chemotherapy or tyrosine kinase inhibitors, MDSCs differentiation using all-trans retinoic acid, and STAT3 inhibition merit clinical evaluation during the perioperative period. In addition, combining low-dose epigenetic drugs with chemokine receptors, reversing immunosuppression through the Enhanced Recovery After Surgery protocol, repairing vascular leakage, or inhibiting extracellular matrix remodeling also may enhance the long-term survival of curative resection patients.

Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors.

INTRODUCTION: Tenosynovial giant cell tumor (TGCT) is a locally aggressive tumor with colony-stimulating factor 1 receptor (CSF1R) signal expression. However, there is a lack of better in vivo and ex vivo models for TGCT. This study aims to establish a favorable preclinical translational platform, which would enable the validation of efficient and personalized therapeutic candidates for TGCT. PATIENTS AND METHODS: Histological analyses were performed for the included patients. Fresh TGCT tumors were collected and sliced into 1.0-3.0 mm3 sections using a sterilized razor blade. The tumor grafts were surgically implanted into subrenal capsules of athymic mice to establish patient-derived tumor xenograft (PDTX) mouse models. Histological and response patterns to CSF1R inhibitors evaluations were analyzed. In addition, ex vivo cultures of patient-derived explants (PDEs) with endpoint analysis were used to validate TGCT graft response patterns to CSF1R inhibitors. RESULTS: The TGCT tumor grafts that were implanted into athymic mice subrenal capsules maintained their original morphological and histological features. The "take" rate of this model was 95% (19/20). Administration of CSF1R inhibitors (PLX3397, and a novel candidate, WXFL11420306) to TGCT-PDTX mice was shown to reduce tumor size while inducing intratumoral apoptosis. In addition, the CSF1R inhibitors suppressed circulating nonspecific monocyte levels and CD163-positive cells within tumors. These response patterns of engrafts to PDTX were validated by ex vivo PDE cultures. CONCLUSIONS: Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.

Is three-dimensional-printed custom-made ultra-short stem with a porous structure an acceptable reconstructive alternative in peri-knee metaphysis for the tumorous bone defect?

BACKGROUND: Long-lasting reconstruction after extensive resection involving peri-knee metaphysis is a challenging problem in orthopedic oncology. Various reconstruction methods have been proposed, but they are characterized by a high complication rate. The purposes of this study were to (1) assess osseointegration at the bone implant interface and correlated incidence of aseptic loosening; (2) identify complications including infection, endoprosthesis fracture, periprosthetic fracture, leg length discrepancy, and wound healing problem in this case series; and (3) evaluate the short-term function of the patient who received this personalized reconstruction system. METHODS: Between September 2016 and June 2018, our center treated 15 patients with malignancies arising in the femur or tibia shaft using endoprosthesis with a 3D-printed custom-made stem. Osseointegration and aseptic loosening were assessed with digital tomosynthesis. Complications were recorded by reviewing the patients' records. The function was evaluated with the 1993 version of the Musculoskeletal Tumor Society (MSTS-93) score at a median of 42 (range, 34 to 54) months after reconstruction. RESULTS: One patient who experienced early aseptic loosening was managed with immobilization and bisphosphonates infusion. All implants were well osseointegrated at the final follow-up examination. There are two periprosthetic fractures intraoperatively. The wire was applied to assist fixation, and the fracture healed at the latest follow-up. Two patients experienced significant leg length discrepancies. The median MSTS-93 score was 26 (range, 23 to 30). CONCLUSIONS: A 3D-printed custom-made ultra-short stem with a porous structure provides acceptable early outcomes in patients who received peri-knee metaphyseal reconstruction. With detailed preoperative design and precise intraoperative techniques, the reasonable initial stability benefits osseointegration to osteoconductive porous titanium, and therefore ensures short- and possibly long-term durability. Personalized adaptive endoprosthesis, careful intraoperative operation, and strict follow-up management enable effective prevention and treatment of complications. The functional results in our series were acceptable thanks to reliable fixation in the bone-endoprosthesis interface and an individualized rehabilitation program. These positive results indicate this device series can be a feasible alternative for critical bone defect reconstruction. Nevertheless, longer follow-up is required to determine whether this technique is superior to other forms of fixation.

Three-dimensional-printed customized prosthesis for pubic defect: clinical outcomes in 5 cases at a mean follow-up of 24 months.

BACKGROUND: Pubic defects resulting from type III hemipelvectomy are commonly not reconstructed due to the need to preserve the weight-bearing axis. However, the opening of the anterior pelvic ring will inevitably lead to increased pelvic instability. To improve long-term pelvic stability, three-dimensional (3D)-printed customized prostheses were designed to reconstruct pubic defects. This study presents and evaluates the short-term clinical outcomes and complications from the use of this construct. METHODS: Five patients who underwent type III hemipelvectomy and 3D-printed customized prosthesis reconstruction at our institution between 2017 and 2019 were retrospectively analysed. Operation time and blood loss during the operation were recorded. Local and functional recovery was assessed. Prosthetic position and osseointegration were evaluated. Oncology results and complications were recorded. RESULTS: The prostheses consisted of three with stems and two without. The mean follow-up time was 23.6 months. At the last follow-up, all five patients were alive with no evidence of disease. No deep infections or local recurrence had occurred. The mean blood loss and mean intraoperative time were 1680 ml and 294 min, respectively. The mean functional MSTS score at the final follow-up was 29.8. Fretting wear around the prosthetic stem was found in 3 patients, while bone wear on the normal-side pubis was found in 2 patients. Osseointegration was observed in all patients. CONCLUSIONS: 3D-printed customized prostheses for reconstructing pubic bone defects after type III hemipelvectomy showed acceptable early outcomes. The good outcomes were inseparable from the precision prosthesis design, strict surgical procedures, and sensible postoperative management.

Long-term results of uncemented allograft prosthesis composite reconstruction for the tumor in proximal femur: a minimum follow-up of sixty-five months.

BACKGROUND: Uncemented allograft prosthesis composite (APC) has been applied for tumorous bone defect reconstruction in the proximal femur. However, the long-term results are rarely reported. This study aimed to evaluate long-term outcomes of uncemented APC. METHODS: Eighteen patients who received uncemented APC reconstruction in the proximal femur after tumor resections were retrospectively reviewed. RESULTS: The average resection length was 110 mm (80-154) and the average follow-up was 106.7 months (65-141). Bone union achieved in all patients with an average duration of 7.6 months (5-10). The average HHS, MSTS score and gluteus medius strength at one-year follow-up were 88.0 (80-94), 25.2 (22-28) and 4 (3-5), respectively. While at the last follow-up, the HHS, MSTS score and gluteus medius strength were 83.0 (48-100), 24.0 (10-30) and 4 (2-5), respectively. Five intraoperative fractures were fixed with cerclage wires. Two postoperative periprosthetic and prosthetic fractures received a revision. Three local recurrent patients received a secondary surgery. One of these three lung metastatic patients underwent lung metastatic tumor resection. Another two patients were diagnosed with both bone and lung metastases, only one of them underwent amputation. Two greater trochanteric fractures received no treatment. There were10 severe, 3 moderate and 5 mild allograft resorptions without treatment. CONCLUSION: Uncemented APC is a reliable reconstruction for neoplastic bone defect of the proximal femur, especially for the young patient who expected long-life expectancy and good function. Though allograft resorption and trochanteric fracture are the common complications, they seem no effect on the function.