Discoidin Domain Receptor Tyrosine Kinase 1 (DDR1) Is a Novel Therapeutic Target in Liposarcoma: A Tissue Microarray Study.

BACKGROUND: Liposarcoma is the most commonly diagnosed subtype of soft tissue sarcoma. As these tumors often arise near vital organs and neurovascular structures, complete resection can be challenging; consequently, recurrence rates are high. Additionally, available chemotherapeutic agents have shown limited benefit and substantial toxicities. There is, therefore, a clear and unmet need for novel therapeutics for liposarcoma. Discoidin domain receptor tyrosine kinase 1 (DDR1) is involved in adhesion, proliferation, differentiation, migration, and metastasis in several cancers. However, the expression and clinical importance of DDR1 in liposarcoma are unknown. QUESTIONS/PURPOSES: The purposes of this study were to assess (1) the expression, (2) the association between DDR1 and survival, and (3) the functional roles of DDR1 in liposarcoma. METHODS: The correlation between DDR1 expression in tumor tissues and clinicopathological features and survival was assessed via immunohistochemical staining of a liposarcoma tissue microarray. It contained 53 samples from 42 patients with liposarcoma and 11 patients with lipoma. The association between DDR1 and survival in liposarcoma was analyzed by Kaplan-Meier plots and log-rank tests. The DDR1 knockout liposarcoma cell lines were generated by CRISPR-Cas9 technology. The DDR1-specific and highly selective DDR1 inhibitor 7RH was applied to determine the impact of DDR1 expression on liposarcoma cell growth and proliferation. In addition, the effect of DDR1 inhibition on liposarcoma growth was further accessed in a three-dimensional cell culture model to mimic DDR1 effects in vivo. RESULTS: The results demonstrate elevated expression of DDR1 in all liposarcoma subtypes relative to benign lipomas. Specifically, high DDR1 expression was seen in 55% (23 of 42) of liposarcomas and no benign lipomas. However, DDR1 expression was not found to be associated with poor survival in patients with liposarcoma. DDR1 knockout or treatment of 7RH showed decreased liposarcoma cell growth and proliferation. CONCLUSION: DDR1 is aberrantly expressed in liposarcoma, and it contributes to several markers of oncogenesis in these tumors. CLINICAL RELEVANCE: This work supports DDR1 as a promising therapeutic target in liposarcoma.

Validation of a Diagnostic Model to Differentiate Multiple Myeloma from Bone Metastasis.

Purpose: A diagnostic model to differentiate multiple myeloma (MM) from bone metastasis (BM) in patients with destructive bone lesions (MM-BM DDx) was developed to promote timely and appropriate referral of patients with MM to hematologists. External validation has never been conducted. This study aims to externally validate the performance of the MM-BM DDx model. Patients and Methods: This multi-center external validation study was conducted using retrospective data of patients over 45 years old diagnosed with MM or BM at six university-affiliated hospitals in Thailand from 2016 to 2022. The MM-BM DDx development dataset, including patients from 2012 to 2015, was utilized during external validation. Diagnostic indicators for MM included in the MM-BM DDx model are serum creatinine, serum globulin, and serum alkaline phosphatase (ALP). MM and BM diagnosis was based on the documented International Classification of Diseases 10th Revision codes. Model performance was evaluated in terms of discrimination, calibration, and accuracy. Results: A total of 3018 patients were included in the validation dataset (586 with MM and 2432 with BM). Clinical characteristics were similar between the validation and development datasets. The MM-BM DDx model's predictions showed an AUC of 0.89 (95% CI, 0.87, 0.90). The predicted probabilities of MM from the model increased concordantly with the observed proportion of MM within the validation dataset. The estimated sensitivity, specificity, and LR for each odds class in the validation dataset were similar to those of the development dataset. Conclusion: The discriminative ability and calibration of the MM-BM DDx model were found to be preserved during external validation. These findings provide support for the practical use of the MM-BM DDx model to assist clinicians in identifying patients with destructive bone lesions who are likely to have MM and enable them to arrange timely referrals for further evaluation by hematologists.

Subdeltoid Lipoma Associated With Subscapularis Tear Successfully Treated With Arthroscopic Resection and Cuff Repair: A Case Report.

A 61-year-old male patient presented with left shoulder pain and an associated lump. Magnetic resonance imaging revealed a subscapularis tear, and subdeltoid lipoma obliterated its insertion. He was successfully treated with arthroscopic subscapularis repair and resection of mass simultaneously.To the authors' knowledge, this will be the first documented case of lipoma occurring under the deltoid muscle associated with the subscapularis tear. The reported arthroscopic approach for resection of the subdeltoid lipoma provides a complete removal, minimal muscle dissection, limited surgical scar, and satisfying functional outcomes. Therefore, it may be considered an option for benign tumor resection in this area.

En bloc resection and vascularized ulnar pedicle graft reconstruction with plate fixation for giant cell tumour of the distal radius.

We retrospectively reviewed the medical records of ten patients (five men and five women) who were treated in our unit for Campanacci Grade III giant cell tumour of the distal radius between July 2017 and December 2019. Following en bloc resection of a giant cell tumour of the distal radius, the wrist was reconstructed by transposing a vascularized pedicle graft from the ipsilateral ulnar shaft. The graft was fixed to the radial shaft and proximal carpal row with plates. At a mean follow-up of 23.5 months (range 18 to 31), bony union was achieved in all cases and there were no tumour recurrences. All patients had a good range of pronation and supination, but flexion and extension of the wrist was limited. DASH scores ranged from 5 to 11. This reconstruction method is a safe and effective procedure that provides good aesthetic outcomes, removes the need for microvascular techniques and reduces donor site morbidity.Level of evidence: IV.

Outcomes of 2-octyl cyanoacrylate skin adhesives following musculoskeletal oncology surgery: A STROBE-compliant observational study.

ABSTRACT: 2-octyl cyanoacrylate (2OCA) is a high-viscosity medical-grade tissue adhesive that is routinely used. However, no studies have evaluated its use in musculoskeletal surgery.We enrolled 99 patients who underwent musculoskeletal surgery. 2OCA was chosen for wound closure and was performed by a specific surgeon for all patients. The drying times for the adhesive were recorded, and photographs were obtained intra-operatively. Posttreatment follow-up consisted of queries regarding pain level and recording incisional dehiscence, wound infection, hematoma, and incisional bleeding. Data collection was performed postoperatively at 48 hours, 5 to 10 days, 14 days, and 30 days. Other adverse events were documented.2OCA was applied to 110 incisions in 99 patients, comprising 62 female and 37 male patients. The mean age of patients was 50.41 (±16.83) years; mean incision length was 10.24 (±5.7) cm, and the mean pain score using a visual analogue scale was 2.37 on a postoperative day 7. The mean drying time was 1.81 (±0.59) minutes; 91 (91%) patients reported excellent and superior satisfaction, and the remaining patients reported "good" (6%) and "fair" (2%) satisfaction. The percentages of dehiscence, hematoma and keloid formation were considerably low.In this study, 2OCA was safe for musculoskeletal oncology surgical incisions. The incidence of postoperative adverse events was low. However, some patients develop hematomas. Postoperative pain was low, and patient satisfaction was high. 2OCA can be a practical alternative to traditional suture closure for skin incisions after musculoskeletal surgery.

T-LAK cell-originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma.

T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK) is an emerging target with critical roles in various cancers; however, its expression and function in osteosarcoma remain unexplored. We evaluated TOPK expression using RNA sequencing and gene expression data from public databases (TARGET-OS, CCLE, GTEx, and GENT2) and immunohistochemistry in an osteosarcoma tissue microarray (TMA). TOPK gene expression was significantly higher in osteosarcoma than normal tissues and directly correlated with shorter overall survival. TOPK was overexpressed in 83.3% of the osteosarcoma specimens within our TMA and all osteosarcoma cell lines, whereas normal osteoblast cells had no aberrant expression. High expression of TOPK associated with metastasis, disease status, and shorter overall survival. Silencing of TOPK with small interfering RNA (siRNA) decreased cell viability, and inhibition with the selective inhibitor OTS514 suppressed osteosarcoma cell proliferation, migration, colony-forming ability, and spheroid growth. Enhanced chemotherapeutic sensitivity and a synergistic effect were also observed with the combination of OTS514 and either doxorubicin or cisplatin in osteosarcoma cell lines. Taken together, our study demonstrated that TOPK is a potential prognostic biomarker and therapeutic target for osteosarcoma treatment.

Ketorolac plus Lidocaine vs Lidocaine for pain relief following core needle soft tissue biopsy: A CONSORT-compliant double-blind randomized controlled study.

BACKGROUNDS: The main objective of this study was to compare the pain control efficacy of local administration of Lidocaine with or without the nonsteroidal anti-inflammatory drug, Ketorolac, and local conventional Lidocaine injection in core needle biopsy of the musculoskeletal tumor. METHODS: The current study was a randomized, double-blind controlled clinical trial that included 128 patients with suspected musculoskeletal tumors. Patients were randomly assigned to either the Ketorolac plus Lidocaine (n = 64) or Lidocaine group (n = 64). The Ketorolac - Lidocaine combination syringe contained 30 mg Ketorolac and 2% Lidocaine - adrenaline dosage, and the Lidocaine syringe contained 2% Lidocaine - adrenaline dosage. The level of pain after core needle biopsy was evaluated for each patient at 1, 6, 12, 24, 48, and >48 hours by a Visual Analog Scale (VAS). The mean VAS changes over time were compared between the Ketorolac plus Lidocaine and Lidocaine groups using a linear mixed model. RESULTS: baseline information including mean age of patients in Lidocaine group (51.5 ±â€Š19.4 years) and in Lidocaine - Ketorolac combination group (50.1 ±â€Š18 years), diagnosis (malignant, benign, metastatic, infection), tumor location (upper and lower extremities, back), VAS score 1-hour post-operation (mild and moderate pain) were noted. The VAS score ratings were significantly lower in Lidocaine - Ketorolac combination group when compared to the Lidocaine group during the 1 to 24 hours post-operation time period. CONCLUSION: Patients receiving Lidocaine - Ketorolac combination dosage had significantly lower VAS scores, and these results confirm that local injection of Lidocaine - Ketorolac combination had a superior pain-controlling effect during the first 24 hours after the biopsy procedure in comparison to Lidocaine injection alone, as measured by VAS score scale.

Prognostic Significance of Cyclin E1 Expression in Patients With Chordoma: A Clinicopathological and Immunohistochemical Study.

PURPOSE: Chordomas are rare, slow-growing sarcomas without any accepted prognostic biomarkers. Owing to their proximity to critical neurovascular structures, discovering predictive biomarkers in chordoma has been a significant research effort because it may potentially reduce risky therapies in patients with less aggressive tumors. In response, because cyclin E1 overexpression correlates with patient prognosis in several malignancies, we investigated its expression in chordoma and whether it informs patient prognosis. METHODS: Seventy-five chordoma patient specimens were enrolled in a tissue microarray (TMA) to evaluate cyclin E1 expression via immunohistochemical staining. Western blot was used to assess cyclin E1 expression in chordoma cell lines and fresh tissues. We then correlated cyclin E1 staining intensity in the TMA to clinicopathological features and chordoma patient outcomes. RESULTS: Sixty-three percent of the chordoma patient specimens in the TMA, fifty-six percent of the fresh chordoma tissues, and all chordoma cell lines showed high cyclin E1 expression. In TMA analysis, cyclin E1 expression positively correlated to chordoma patient disease status. By survival analysis, high cyclin E1 expression was an independent prognostic risk factor for chordoma patients along with advanced disease status and positive surgical margin. CONCLUSION: Cyclin E1 is a promising biomarker predicting chordoma patient prognosis.

T-LAK cell-originated protein kinase (TOPK) is a Novel Prognostic and Therapeutic Target in Chordoma.

OBJECTIVES: To assess the expression, prognostic value, and functionality of T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK) in chordoma pathogenesis. MATERIALS AND METHODS: TOPK expression in chordoma was assessed via immunohistochemical staining of a tissue microarray (TMA) and correlated with patient clinicopathology. TOPK expression in chordoma cell lines and fresh patient tissues was then evaluated by Western blot. TOPK small interfering RNA (siRNA) and the specific inhibitor OTS514 were applied to determine the roles of TOPK in chordoma pathogenicity. The effect of TOPK expression on chordoma cell clonogenicity was also investigated using clonogenic assays. A 3D cell culture model was utilized to mimic in vivo environment to validate the effect of TOPK inhibition on chordoma cells. RESULTS: TOPK was highly expressed in 78.2% of the chordoma specimens in the TMA and all chordoma cell lines. High TOPK expression significantly correlated with metastasis, recurrence, disease status and shorter overall survival. Knockdown of TOPK with specific siRNA resulted in significantly decrease chordoma cell viability. Inhibition of TOPK with OTS514 significantly inhibited chordoma cell growth and proliferation, colony-forming capacity and ex vivo spheroid growth. CONCLUSIONS: High expression of TOPK is an important predictor of poor prognosis in chordoma. Inhibition of TOPK resulted in significantly decrease chordoma cell proliferation and increase apoptosis. Our results indicate TOPK as a novel prognostic biomarker and therapeutic target for chordoma.

The reconstruction after en-bloc resection of giant cell tumors at the distal radius: A systematic review and meta-analysis of the ulnar transposition reconstruction technique.

BACKGROUND: En-bloc resection of giant cell tumors (GCTs) of the distal radius remains the mainstay treatment for those with high-graded lesions. Several techniques have been described for reconstruction of the resected segment, of which transposition of the ipsilateral ulna is scarcely reported. OBJECTIVES: To investigate the efficacy and safety of the different techniques of ulnar translocation following GCTs total resection. METHODS: A systematic review and meta-analysis was conducted concerning the reported functional outcomes, including grip strength, range of forearm motion, functional scores, and new bone formation, as well as postoperative complications, such as delayed union, local recurrence and metastasis. The ranges of functional outcomes were reviewed and the pooled prevalence rates of complication and their respective 95% confidence intervals (95% CIs) were computed. RESULTS: In a total of 12 studies, 90 patients (51.1% males, 84.8% had Campanacci grade III tumors) underwent five different reconstruction techniques. As compared to the normal side, the mean grip strength in the affected side ranged between 59 and 71%. The average union time was 1-8 months, while delayed union was reported in 50% (95% CI, 15.35 to 84.65) of patients whom their grafts were fixed with Steinmann pins. The shortest union time, the highest forearm supination and pronation degrees, new bone formation at the ulnar stump, and the highest functional scores were reported following a modified distal radius plate technique. Using a dynamic compression plate and a clover leaf plate provided lower, but considerable, functional outcomes. CONCLUSION: Ulnar translocation following GCT en-bloc resection warrants additional investigation in large cohorts and well-designed studies to corroborate the promising outcomes presented in this review.

Cyclin-dependent kinase 12 (CDK12) in chordoma: prognostic and therapeutic value.

PURPOSE: To determine the cyclin-dependent kinase 12 (CDK12) expression in chordoma patient tissues and cell lines, its correlation with oncologic outcomes, and its function in chordoma cell proliferation. METHODS: A chordoma tissue microarray was constructed from fifty-six patient specimens and examined by immunohistochemistry to measure CDK12 expression and its correlation to patient clinical characteristics and survival. CDK12 expression in chordoma cell lines and patient tissues was evaluated via western blot. CDK12 specific small interfering RNA (siRNA) was applied to determine whether its inhibition attenuated chordoma cell growth and proliferation. RESULTS: CDK12 was expressed in the majority of chordoma specimens, with notably higher expression in patients with recurrent or metastatic disease. High CDK12 expression was an independent prognostic predictor for shorter overall and progression-free survival in chordoma by univariate and multivariate analysis. Western blot analysis revealed that CDK12 was also highly expressed in chordoma cell lines, with CDK12 specific small interfering RNA (siRNA) mediated knockdown decreasing proliferation and inducing apoptosis. Mechanistically, inhibition of CDK12 decreased phosphorylation of RNA polymerase II (RNAP II) and the anti-apoptotic proteins Survivin and Mcl-1. CONCLUSION: High expression of CDK12 is an independent predictor of poor prognosis in chordoma. Inhibition of CDK12 significantly decreased chordoma cell proliferation and induced apoptosis. Our results support CDK12 as a novel prognostic biomarker and therapeutic target in chordoma.

Cyclin E1 is a prognostic biomarker and potential therapeutic target in osteosarcoma.

While amplified expressed cyclin E1 is a well-known tumorigenic factor and prognostic biomarker in several malignancies, its prognostic predictive potential and function in osteosarcoma is poorly understood. Here we reveal discrete expression pattern, correlation to clinicopathological characteristics and prognosis and overall function of cyclin E1 in osteosarcoma. Sixty-nine osteosarcoma patient tumor specimens were enrolled to construct a tissue microarray to evaluate cyclin E1 expression through immunohistochemical staining. Cyclin E1 expression in osteosarcoma cell lines and fresh tissues was assessed by Western blot. Cyclin E1 gene expression was evaluated using RNA sequencing data acquired from the public database. We correlated staining intensity to clinical characteristics. Cyclin E1 small interfering RNA was used to determine the effect of cyclin E1 silencing on osteosarcoma cell proliferation and chemotherapeutic sensitivity. Sixty-one percent of the osteosarcoma patient specimens in the tissue microarray had high cyclin E1 expression. Cyclin E1 gene was significantly highly expressed in osteosarcoma tissues and cell lines compared to normal tissues. The expression of cyclin E1 positively correlated with disease status, and inversely correlated to prognosis and response to neoadjuvant chemotherapy. The expression of cyclin E1 was an independent prognostic factor for osteosarcoma patients. In addition, silencing cyclin E1 expression in osteosarcoma cells significantly inhibited cell proliferation and increased sensitivity to chemotherapeutics. We conclude that cyclin E1 is overexpressed in osteosarcoma and is a promising biomarker for prognosis and chemotherapeutic response. We confirm aberrant cyclin E1 expression is a potent therapeutic target in osteosarcoma, and its selective inhibition is a rational treatment strategy for osteosarcoma.

Establishment and Characterization of a Recurrent Osteosarcoma Cell Line: OSA 1777.

Osteosarcoma (OSA) is the most common primary bone malignancy overall and is responsible for considerable adolescent mortality. Approximately 850 patients are newly diagnosed with OSA in the United States each year. While the 5-year survival rate for localized OSA has improved from <20% over 40 years ago to over 65% today, progress has dwindled over the past three decades. Therapeutic stagnation has occurred, in part, as a result of limited preclinical models and the overall heterogeneity of OSA among patients. In this study, we report the establishment and characterization of a novel OSA cell line: OSA 1777. This cell line was isolated from the recurrent tumor specimen of a 19-year-old female who initially experienced 99% tumor necrosis after neoadjuvant chemotherapy and eventually had local recurrence and metastases. We present OSA 1777 growth characteristics, tumor markers, chemotherapeutic sensitivities, and oncogenic spheroid formation. In a two-dimensional (2D) monolayer culture, OSA 1777 exhibited a spindle shape and 60 h doubling time. STR DNA profiling revealed a unique genomic identity not matching any existing human cancer cell lines from the ATCC or DSMZ databases. Consistent with the mesenchymal origin, western blot was positive for vimentin and negative for the carcinoma marker cytokeratin. Within three-dimensional (3D) culture, the cells formed spheroids of similar patterning and smaller size compared with MNNG-HOS and U2OS cell lines. The chemotherapeutic drug sensitivity of OSA 1777 was evaluated in both 2D and 3D culture systems. In summary, we report OSA 1777 as a novel biological model of OSA amenable to future studies focused on OSA that recurs despite an initially strong chemotherapeutic response. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:902-910, 2020.

Cancer testis antigens in sarcoma: Expression, function and immunotherapeutic application.

Sarcomas are a group of heterogeneous malignancies of mesenchymal origin. Patient outcomes remain especially grim for those with recurrent or metastatic disease, and current therapeutic strategies have not significantly improved outcomes over the past few decades. This has led to a number of studies assessing novel therapies. Cancer testis antigens (CTAs) are tumor-associated antigens with physiologic expression in the testis and various malignancies, including sarcomas. Genes encoding CTAs include MAGE, NY-ESO-1, PRAME, TRAG-3/CSAGE, and SSX. The importance and function of CTAs in tumorigenesis have gained recognition in recent years. They are also proving as robust diagnostic and prognostic biomarkers. Therapeutically, antigens derived from CTAs are highly recognizable by T lymphocytes and therefore capable of generating a potent antitumor immune response. CTAs are, therefore, promising targets for novel immunotherapies. Here we review the emerging works on expression, function, and immunotherapeutic application of CTAs in sarcoma therapy.

Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications.

Survival rates for sarcoma patients have plateaued in the past few decades and remain especially grim for those with recurrent or metastatic disease. This has prompted investigation into novel immunotherapies for sarcomas, especially after their recent and well-recognized successes in other cancers. One such modality, the Chimeric Antigen Receptor (CAR) T Cell therapy, has shown promising results in treating B-cell lymphoma and acute lymphoblastic leukemia. This novel therapy functions by fusing a specific antibody derived single-chain variable fragment (scFv) with a T-cell which recognizes a specific tumor-associated antigen (TAA). Several sarcoma-associated antigens (SAA) amenable to CAR-T cell treatment have recently emerged with encouraging results. These include human epidermal growth factor receptor 2 (HER2), disialoganglioside (GD2), interleukin 11 Receptor Subunit Alpha (IL-11RA), fibroblast activation protein (FAP), B7-H3, CD44v6, insulin-like growth factor 1 receptor (IGF-1R), and tyrosine kinase orphan-like receptor 1 (ROR1). Given the limitations of current medical therapies, novel treatment strategies are urgently needed. As a sarcoma treatment modality, CAR-T cell therapy is highly promising and continues to draw interest especially as new clinical trials emerge. Here we review recent breakthrough CAR-T cell studies in sarcoma, the targets which define them, and approaches to minimizing host cytotoxicity.

Glomus tumor of uncertain malignant potential of the brachial plexus: A case report.

BACKGROUND: Glomus tumor is an uncommon benign tumor usually presenting with a small mass occurring in the dermis or soft tissue of an extremity, especially subungual region. However, intraneural glomus tumor is sporadic. While most of the glomus tumors are benign, atypical glomus tumors with unusual features can be occasionally found, leading to distinctive malignant potential required different therapeutic approaches. Glomus tumor of uncertain malignant potential is one type of atypical glomus tumor with limited criteria for malignancy and without metastasis. CASE SUMMARY: Herein, we report a case of a 48-year-old Thai male with a large painful mass in his axilla for one year without apparent neurological deficit. Magnetic resonance imaging showed a large heterogeneous mass encasing entire posterior cord of left brachial plexus and axillary artery. The tumor tissue from core needle biopsy histologically demonstrated the sheets and cords of relatively uniform tumor cells with foamy cytoplasm and round to oval hyperchromatic nuclei without atypia. The mitotic count was 0 per 50 high power field. A final diagnosis of glomus tumor of uncertain malignant potential was rendered. Complete surgical resection was performed, followed by adjuvant radiation due to positive margin. Neither local recurrence nor distant metastasis was observed at 2-year follow up. Unfortunately, postoperative incomplete brachial plexopathy without signs of re-innervation by electromyography was persisted. Later nerve grafting reconstruction was performed, followed by ongoing neurological rehabilitation. CONCLUSION: Glomus tumor of uncertain malignant potential is exceedingly rare, especially around brachial plexus. Although the prognosis is good, careful histological diagnosis and treatment are needed to achieve an optimal outcome with lower morbidity.

Advances in immune checkpoint inhibitors for bone sarcoma therapy.

Bone sarcomas are a collection of sporadic malignancies of mesenchymal origin. The most common subtypes include osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. Despite the use of aggressive treatment protocols consisting of extensive surgical resection, chemotherapy, and radiotherapy, outcomes have not significantly improved over the past few decades for osteosarcoma or Ewing sarcoma patients. In addition, chondrosarcoma and chordoma are resistant to both chemotherapy and radiation therapy. There is, therefore, an urgent need to elucidate which novel new therapies may affect bone sarcomas. Emerging checkpoint inhibitors have generated considerable attention for their clinical success in a variety of human cancers, which has led to works assessing their potential in bone sarcoma management. Here, we review the recent advances of anti-PD-1/PD-L1 and anti-CTLA-4 blockade as well as other promising new immune checkpoint targets for their use in bone sarcoma therapy.

Comparative outcome of PFNA, Gamma nails, PCCP, Medoff plate, LISS and dynamic hip screws for fixation in elderly trochanteric fractures: a systematic review and network meta-analysis of randomized controlled trials.

The ideal implant for the treatment of an unstable intertrochanteric femoral fracture is still a matter of discussion. The aim of this systematic review is to conduct a network meta-analysis of randomized controlled trials (RCTs) comparing clinical outcomes between dynamic hip screws (DHS), Medoff sliding plating, percutaneous compression plating (PCCP), proximal femoral nails (PFN), Gamma nails and less invasive stabilization system fixation in femoral trochanteric fractures in the elderly. These clinical outcomes consist of total intra-operative time, intra-operative fluoroscopy time, intra-operative blood loss, blood component transfusion, length of hospital stay, postoperative general complications, wound complications, late complications and reoperation rates. This systematic review was conducted using PubMed and Scopus search engines for RCTs comparing clinical outcomes between treatments from inception to February 22, 2015. Thirty-six of 785 studies identified were eligible. Compared to the other implants, PCCP showed the lowest total operative time and units of blood transfusion with an unstandardized mean difference (UMD) of 29.27 min (95% CI 5.24, 53.50) and 0.89 units (95% CI 0.52, 1.25). The lowest incidence of general complications, wound complications and late complications of PCCP was 0.09 (95% CI 0.04, 0.18), 0.01 (95% CI 0.01, 0.04) and 0.05 (95% CI 0.02, 0.11), respectively, when compared to others. The lowest fluoroscopic time was with DHS with an UMD of 0.24 min (95% CI 0.16, 0.32), whereas the lowest blood loss and shortest hospital stay were with PFN with an UMD of 233.61 ml of blood loss (95% CI 153.17, 314.04) and 7.23 days of hospital stay (95% CI 7.15, 7.31) when compared to all other fixation methods. Reoperation rates of all implants had no statistically significant difference. The network meta-analysis suggested that fixation with PCCP significantly shortens operative time and decreases the units of blood transfusion required, while also lowering risks of general complications, wound complications and late complications when compared to fixation. Use of PFN showed the least intra-operative blood loss and shortest hospital stay. Multiple active treatment comparisons indicate that PCCP fixation in trochanteric fractures in the elderly is the treatment of choice in terms of intra-operative outcomes and postoperative complications.