-

Abstract-An exciting approach to cancer treatment has been offered by the progress in the development of nanoscale drug delivery systems. An exceptional characteristic of these nanosystems lies in their capacity to stimulate the immune system, which could be the foundation for the design of a cancer vaccine. The current mini-review focuses on the role that the nanoparticles may play as anticancer immunizers

Hemiarthroplasty versus reverse shoulder arthroplasty in 4-part displaced fractures of the proximal humerus: Multicenter retrospective study

Introduction: Complex 4-part fractures of the proximal humerus are one of the most difficult fractures to manage. For several years, reverse total arthroplasty (RSA) has been proposed as an alternative to hemiarthroplasty (HA) when internal fixation is insufficient. The goal of this study was to compare the short and intermediate term results of these 2 different types of arthroplasty. Materials and methods: In a retrospective, multicenter study, 57HA and 41 RSA were reviewed after a follow-up of at least 2 years. The clinical evaluation was based on the absolute and adjusted Constant scores, Simple shoulder value (SSV) and the quick-DASH scores. The radiological assessment included standard radiological tests. Results: After a mean follow-up of 39 months, the RSA group had a significantly higher adjusted Constant score than the HA group (83% vs 73%, respectively P = 0.02). However, there was no significant difference in the absolute Constant score, the quick-DASH or the SSV scores. Active anterior elevation was better in the RSA group, while internal rotation was better in the HA group (130◦ vs 112◦, P = 0.01; sacrum vs L3, P = 0.03). There was no significant difference in external rotation (28◦ vs 23◦, P = 0.31). The rate of complications was higher in the HA group than in the RSA group (24% vs 10%, P = 0.01). The radiological rate of union of the greater tuberosity was similar in both groups (70%) and scapular notching was found in 23% of the RSA group. Conclusion: The short and intermediate term clinical outcomes are better with RSA than with HA. The complication rate is higher with HA. Nevertheless, scapular notching occurred in more than 20% of patients with RSA, suggesting that care should be taken when using this prosthesis in young, active patients

Four-part fractures treated with a reversed total shoulder prosthesis: Prospective and retrospective multicenter study. Results and complications

Introduction: The reversed shoulder prosthesis is becoming the gold standard for cases of complex fracture of the proximal humerus after 70 years of age. Material and methods: The French Society of Orthopaedic and Traumatology Surgery (SOFCOT) conducted a prospective and retrospective multicenter study to evaluate the results of the reversed shoulder prosthesis implanted in patients with a four-part fracture in nine centers. In the retrospective study (n = 41 patients, 78 years of age, 14% ASA grade 3, 21% associated fractures) and in the prospective study (n = 32 patients, 79 years of age, 37% ASA grade 3, 21% associated fractures) evaluation by independent surgeons was conducted to measure the QuickDASH score, the Constant score, the SSV (subjective shoulder value), and complications to correlate these measurements with radiological results. Results: In both studies, use of an autograft (75%) to perform an osteosuture of tuberosities (90%) and no postoperative immobilization (75%) were similar. In the retrospective study at 39 months (range: 24–62 months) of follow-up, the QuickDASH reached 28 (range: 0–59), the Constant scores (raw Constant = 57, weighted Constant = 83.4%), and SSV 75 (range: 35–100). Complications after the 1st month (7%) were nonunion or ossifications. In the prospective study at 11 months (range: 5–16.5 months) of follow-up, the QuickDASH reached 40 (range: 1–75), the Constant scores 50 (raw Constant) and 74.6% (weighted Constant), and SSV 69 (range: 10–100). Complications after the 1st month (21%) were stiffness and dislocation, with two patients who underwent revision surgery. In both studies, early complications reached 6% (palsy, dislocation). Conclusion: This double (retrospective and prospective) study confirms the good results with a low level of complications of the reversed implant in cases of fracture but with osteosuture of tuberosities

MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA)

We investigated a hereditary syndrome in Cane Corso dogs. Affected dogs developed dental-skeletal-retinal anomaly (DSRA), clinically characterized by brittle, discolored, translucent teeth, disproportionate growth and progressive retinal degeneration resulting in vision loss. Combined linkage and homozygosity mapping delineated a 5.8 Mb critical interval. The comparison of whole genome sequence data of an affected dog to 789 control genomes revealed a private homozygous splice region variant in the critical interval. It affected the MIA3 gene encoding the MIA SH3 domain ER export factor 3, which has an essential role in the export of collagen and other secreted proteins. The identified variant, XM_005640835.3:c.3822+3_3822+4del, leads to skipping of two exons from the wild type transcript, XM_005640835.3:r.3712_3822del. Genotypes at the variant were consistent with monogenic autosomal recessive mode of inheritance in a complete family and showed perfect genotype-phenotype association in 18 affected and 22 unaffected Cane Corso dogs. MIA3 variants had previously been shown to cause related phenotypes in humans and mice. Our data in dogs together with the existing functional knowledge of MIA3 variants in other mammalian species suggest the MIA3 splice defect and a near complete loss of gene function as causative molecular pathomechanism for the DSRA phenotype in the investigated dogs

Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND: Peritoneal carcinomatosis (PC) from gastric cancer has long been regarded a terminal disease with a short median survival. New locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved and suggest improved survival. MATERIALS AND METHODS: A retrospective multicentric study was performed in French-speaking centers to evaluate the toxicity and the principal prognostic factors in order to identify the best indications. All patients had cytoreductive surgery and PIC: hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC). RESULTS: The study included 159 patients from 15 institutions between February 1989 and August 2007. The median follow-up was 20.4 months. HIPEC was the PIC used for 150 procedures. Postoperative mortality and grade 3-4 morbidity rates were 6.5 and 27.8%, respectively. By multivariate analysis, the institution had a significant influence on toxicity. The overall median survival was 9.2 months and 1-, 3-, and 5-year survival rates were 43, 18, and 13%, respectively. The only independent prognostic indicator by multivariate analysis was the completeness of cytoreductive surgery. For patients treated by complete cytoreductive surgery, the median survival was 15 months with a 1-, 3-, and 5-year survival rate of 61, 30, and 23%, respectively. CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with PIC for patients with gastric carcinomatosis may achieve long-term survival in a selected group of patients (limited and resectable PC). The high mortality rate underlines this necessarily strict selection that should be reserved to experienced institutions involved in the management of PC and gastric surgery

Characterization of Biomaterials Intended for Use in the Nucleus Pulposus of Degenerated Intervertebral Discs

Abstract Biomaterials for regeneration of the intervertebral disc must meet complex requirements conforming to biological, mechanical and clinical demands. Currently no consensus on their characterization exists. It is crucial to identify parameters and their method of characterization for accurate assessment of their potential efficacy, keeping in mind the translation towards clinical application. This review systematically analyzes the characterization techniques of biomaterial systems that have been used for nucleus pulposus (NP) restoration and regeneration. Substantial differences in the approach towards assessment became evident, hindering comparisons between different materials with respect to their suitability for NP restoration and regeneration. We have analyzed the current approaches and identified parameters necessary for adequate biomaterial characterization, with the clinical goal of functional restoration and biological regeneration of the NP in mind. Further, we provide guidelines and goals for their measurement

Graft Choice and the Incidence of Osteoarthritis After Anterior Cruciate Ligament Reconstruction: A Causal Analysis From a Cohort of 541 Patients

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is important to prevent knee osteoarthritis. Neither of the 2 most common graft techniques-the patellar tendon (PT) or hamstring tendon (HS) graft-has demonstrated superiority in terms of the long-term osteoarthritis rate. HYPOTHESIS: Based on the International Knee Documentation Committee (IKDC) radiographic grading system, PT grafts decrease the incidence of osteoarthritis by providing better knee stability as compared with HS grafts over 12 years of follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All adults with a first ACL rupture who underwent surgery with a PT or HS graft technique between January 2002 and December 2003 were included in the 2014 French Society of Orthopedic Surgery and Traumatology Symposium database. Baseline characteristics were collected. The primary endpoint was the occurrence of moderate to severe osteoarthritis in each group. The secondary endpoints included clinical subjective evaluations by the IKDC score and Knee injury and Osteoarthritis Outcome Score. To control the differences in baseline characteristics, the data were analyzed with propensity score matching. RESULTS: In the cohort, 541 patients from 18 centers were included: 311 PT and 230 HS ACL reconstructions. The baseline characteristics were similar after inverse probability weighting treatment (IPWT). The occurrence of osteoarthritis was similar after IPWT (19.3% for PT and 19.6% for HS, P = .94). Age at surgery >29 years and IKDC osteoarthritis stage B at the index surgery were identified as risk factors for moderate to severe osteoarthritis. Most functional outcomes were significantly higher in the HS group; however, the difference between groups remained <10 points. Of the 106 patients who needed a medial meniscectomy, the proportion of patients with moderate to severe osteoarthritis was much higher in the HS group (43.5% vs 18.3%, P = .006). However, after IPWT, the difference was not statistically significant. CONCLUSION: At 12 years of follow-up, neither graft technique was superior to the other in terms of the rate of osteoarthritis

International Preoperative Rectal Cancer Management: Staging, Neoadjuvant Treatment, and Impact of Multidisciplinary Teams

BACKGROUND: Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates. METHODS: One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer. RESULTS: One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years' experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventy-four percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p = 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p = 0.0001), MRI for all RC patients (20% vs. 42%, p = 0.03), and ERUS for all RC patients (43% vs. 21%, p = 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR = 5.67, stage II + III RR = 2.98), quality of pathology report (RR = 4.85), and sphincter-saving surgery (RR = 3.81). CONCLUSIONS: There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods

Primary Tumor Versus Liver-First Approach for Synchronous Colorectal Liver Metastases: An Association Française de Chirurgie (AFC) Multicenter-Based Study with Propensity Score Analysis

OBJECTIVES: Multicenter studies comparing the reverse strategy (RS) with the classical strategy (CS) for the management of stage IVA liver-only colorectal cancer (CCR) are scarce. The aim of this study was to compare long-term survival and recurrence patterns following use of the CS and RS. METHOD: This retrospective multicenter review collected data from all consecutive patients with stage IVA liver-only CCR who underwent staged resection of CCR and liver metastases (LM) at 24 French hospitals between 2006 and 2013 and were retrospectively analyzed. Patients who underwent simultaneous liver and CCR resection, those with synchronous extrahepatic metastasis, and those who underwent emergent CCR resection were excluded. Overall survival (OS) and recurrence-free survival (RFS) rates and recurrence patterns were investigated before and after propensity score matching (PSM). RESULTS: A total of 653 patients were included: 587 (89.9%) in the CS group and 66 (10.1%) in the RS group. Compared with the CS patients, RS patients were more likely to have rectal cancer (43.9 vs. 24.9%; p = 0.006), larger liver tumor size (52.5 ± 38.6 vs. 39.6 ± 30 mm; p = 0.01), and more positive lymph nodes (62.1 vs. 44.8%; p = 0.009). OS was not different between the two groups (75 vs. 72% at 5 years; p = 0.77), while RFS was worse in the RS group (24 vs. 33% at 5 years; p = 0.01). Time to recurrence at any site (1.8 vs. 2.4 years, p = 0.024) and intrahepatic recurrence (1.7 vs. 2.2 years, p = 0.014) were significantly shorter in the RS group than in the CS group. After PSM (63 patients in each group), no significant difference was found between the two groups in OS (p = 0.35), RFS (p = 0.62), time to recurrence at any site (p = 0.19), or intrahepatic recurrence (p = 0.13). CONCLUSIONS: In this study, approximately 10% of patients with CCR and synchronous LM were offered surgery with the RS. Both strategies ensured similar oncological outcomes

Transformed canine and murine mesenchymal stem cells as a model for sarcoma with complex genomics

Simple SummarySarcomas are rare cancers of mesenchymal origin, the majority of which are characterized by many copy number alterations, amplifications, or deletions. Because of these complex genomics, it is notoriously difficult to identify driver events of malignant transformation. In this study, we show that murine and canine mesenchymal stem cells (MSCs) can be used to model spontaneous malignant transformation towards sarcomas with complex genomics. We show that these MSCs have an abnormal karyotype, many structural variants, and point mutations at whole genome sequencing analysis, and form sarcomas after injection into mice. Our cross-species analysis reveals that p53 loss is an early event in sarcomagenesis, and it was shown that MSCs with a knock-out in Trp53 transform earlier compared to wild-type MSCs. Our study points to the importance of p53 loss in the transformation process towards sarcomas with complex genomics.Sarcomas are rare mesenchymal tumors with a broad histological spectrum, but they can be divided into two groups based on molecular pathology: sarcomas with simple or complex genomics. Tumors with complex genomics can have aneuploidy and copy number gains and losses, which hampers the detection of early, initiating events in tumorigenesis. Often, no benign precursors are known, which is why good models are essential. The mesenchymal stem cell (MSC) is the presumed cell of origin of sarcoma. In this study, MSCs of murine and canine origin are used as a model to identify driver events for sarcomas with complex genomic alterations as they transform spontaneously after long-term culture. All transformed murine but not canine MSCs formed sarcomas after subcutaneous injection in mice. Using whole genome sequencing, spontaneously transformed murine and canine MSCs displayed a complex karyotype with aneuploidy, point mutations, structural variants, inter-chromosomal translocations, and copy number gains and losses. Cross-species analysis revealed that point mutations in Tp53/Trp53 are common in transformed murine and canine MSCs. Murine MSCs with a cre-recombinase induced deletion of exon 2-10 of Trp53 transformed earlier compared to wild-type murine MSCs, confirming the contribution of loss of p53 to spontaneous transformation. Our comparative approach using transformed murine and canine MSCs points to a crucial role for p53 loss in the formation of sarcomas with complex genomics.Molecular tumour pathology - and tumour geneticsMTG