Feasibility of MRI Radiomics for Predicting KRAS Mutation in Rectal Cancer

The mutation status of KRAS is a significant biomarker in the prognosis of rectal cancer.This study investigated the feasibility of MRI-based radiomics in predicting the mutation status of KRAS with a composite index which could be an important criterion for KRAS mutation in clinical practice.In this retrospective study,a total of 127 patients with rectal cancer were enrolled.The 3D Slicer was used to extract the radiomics features from the MRI images,and sparse support vector machine(SVM)with linear kernel was applied for feature reduction.The radiomics classifier for predicting the KRAS status was then constructed by Linear Discriminant Analysis(LDA)and its performance was evaluated.The composite index was determined with LDA model.Out of 127 rectal cancer subjects,there were 44 KRAS mutation cases and 83 wild cases.A total of 104 radiomics features were extracted,54 features were filtered by linear SVM with L1-norm regularization and 6 features that had no significant correlations within them were finally selected.The radiomics classifier constructed using the 6 features featured an AUC value of 0.669(specificity:0.506;sensitivity:0.773)with LDA.Furthermore,the composite index(Radscore)had statistically significant difference between the KRAS mutation and wild groups.It is suggested that the MRI-based radiomics has the potential in predicting the KRAS status in patients with rectal cancer,which may enhance the diagnostic value of MRI in rectal cancer.

A novel method to reconstruct phylogeny tree based on thechaos game representation

We developed a new approach for the reconstruction of phylogeny trees based on the chaos game representation (CGR) of biological sequences. The chaos game representation (CGR) method generates a picture from a biological sequence, which displays both local and global patterns. The quantitative index of the biological sequence is extracted from the picture. The Kullback-Leibler discrimination information is used as a diversity indicator to measure the dissimilarity of each pair of biological sequences. The new method is inspected by two data sets: the Eutherian orders using concatenated H-stranded amino acid sequences and the genome sequence of the SARS and coronavirus. The phylogeny trees constructed by the new method are consistent with the commonly accepted ones. These results are very promising and suggest more efforts for further developments.

Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

Background：High-dose methotrexate （HD-MTX） with folinic acid （leucovorin） rescue is ＆quot;gold standard＆quot; therapy for osteosarcoma.Plasma concentrations of methotrexate （MTX） are closely related to its efficacy and toxicity.Delayed excretion of MTX can lead to serious adverse reactions that may result in treatment cessation,irreversible organ damage,and death.This study focused on the incidence of delayed excretion of MTX in Chinese osteosarcoma patients.Methods：A total of 1277 osteosarcoma patients were treated with HD-MTX chemotherapy （4291 cycles） from 2010 to 2015.Factors that could influence delayed excretion of MTX （gender,age,number of chemotherapy cycles,and serum concentration of MTX） were analyzed.Results：The incidence of delayed excretion of MTX （serum concentrations at 24 h [C24 h] 〉5 μmol/L） and severe delayed excretion of MTX （C24 h 〉20 μmol/L） were 6.19% and 0.86% per patient,and 2.31% and 0.26% per cycle of treatment,respectively.The incidence of severe delayed excretion of MTX was associated with gender,age,and C24 h.Conclusions：Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX.An optimal individualized rescue strategy can be created with consideration of gender,age,and C24 h.

Computer Navigation-aided Resection of Sacral Chordomas

Background： Resection of sacral chordomas is challenging. The anatomy is complex, and there are often no bony landmarks to guide the resection. Achieving adequate surgical margins is, therefore, difficult, and the recurrence rate is high. Use of computer navigation may allow optimal preoperative planning and improve precision in tumor resection. The purpose of this study was to evaluate the safety and feasibility of computer navigation-aided resection of sacral chordomas. Methods： Between 2007 and 2013, a total of 26 patients with sacral chordoma underwent computer navigation-aided surgery were included and followed for a minimum of 18 months. There were 21 primary cases and 5 recurrent cases, with a mean age of 55.8 years old （range： 35 84 years old）. Tumors were located above the level of the $3 neural foramen in 23 patients and below the level of the $3 neural foramen in 3 patients. Three-dimensional images were reconstructed with a computed tomography-based navigation system combined with the magnetic resonance images using the navigation software. Tumors were resected via a posterior approach assisted by the computer navigation. Mean follow-up was 38.6 months （range： 18-84 months）. Results： Mean operative time was 307 min. Mean intraoperative blood loss was 3065 ml. For computer navigation, the mean registration deviation during surgery was 1.7 ram. There were 18 wide resections, 4 marginal resections, and 4 intralesional resections. All patients were alive at the final follow-up, with 2 （7.7%） exhibiting tumor recurrence. The other 24 patients were tumor-free. The mean Musculoskeletal Tumor Society Score was 27.3 （range： 19-30）. Conclusions： Computer-assisted navigation can be safely applied to the resection of the sacral chordomas, allowing execution of preoperative plans, and achieving good oncological outcomes. Nevertheless, this needs to be accomplished by surgeons with adequate experience and skill.

Computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction for bone sarcomas:long-term outcomes

Background:Computed tomography(CT)and magnetic resonance imaging(MRI)data can be fused to identify the tumor boundaries.This enables surgeons to set close but tumor-free surgical margins and excise the tumor more precisely.This study aimed to report our experience in performing computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction to treat bone sarcoma in the diaphysis and metaphysis of the femur and tibia.Methods:Between September 2008 and December 2015,24 patients with bone sarcomas underwent surgical resection and joint-sparing reconstruction under image-guided computer navigation.The cohort comprised 16 males and eight females with a median age of 19.5 years(range:12-48 years).The tumor location was the femoral diaphysis in three patients,distal femur in 19,and proximal tibia in two.The tumors were osteosarcoma(n=15),chondrosarcoma(n=3),Ewing sarcoma(n=3),and other sarcomas(n=3).We created a pre-operative plan for each patient using navigation system software and performed navigation-aided resection before reconstructing the defect with a custom-made prosthesis with extracortical plate fixation.Results:Pathological examination verified that all resected specimens had appropriate surgical margins.The median distance from the tumor resection margin to the joint was 30 mm(range:13-80 mm).The median follow-up duration was 62.5 months(range:24-134 months).Of the 24 patients,21 remain disease free,one is alive with disease,and two died of the disease.One patient developed local recurrence.Complications requiring additional surgical procedures occurred in six patients,including one with wound hematoma,one with delayed wound healing,one with superficial infection,one with deep infection,and two with mechanical failure of the prosthesis.The mean Musculoskeletal Tumor Society score at the final follow-up was 91%(range:80%-100%).The 5-and 10-year implant survival rates were 91.3%and 79.9%,respectively.Conclusions:Computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction with extracortical plate fixation is a reliable surgical treatment option for bone sarcoma in the diaphysis and metaphysis of the femur and tibia.

Is There a Reliable Method to Predict the Limb Length Discrepancy after Chemotherapy and Limb Salvage Surgery in Children with Osteosarcoma？

Background： For a child with osteosarcoma, prediction of the limb length discrepancy at maturity is important when planning for limb salvage surgery. The purpose of this study was to provide a reliable prediction method. Methods： A retrospective review of Chinese children receiving chemotherapy for osteosarcoma before skeletal maturity was conducted. Standing full-length radiographs of the lower extremity were used for length measurements. Length-for-age curves were constructed using the LMS method. The lower limb multiplier for a specific age and gender was calculated using the formula M =Lm/L, where M was the gender- and age-specific multiplier, Lm was the bone length at maturity, and L was the age-specific bone length. Prematurity and postmaturity radiographs were used to assess the accuracy of the prediction methods. Results： A total of 513 radiographs of 131 boys and 314 radiographs of 86 girls were used to calculate the coefficients of the multiplier. The multipliers of 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, and 18-year-old boys after chemotherapy for osteosarcoma were 1.394, 1.306, 1.231, 1.170, 1.119, 1.071, 1.032, 1.010, 1.004, 1.001, and 1.000, respectively; while for girls at the same ages, the multipliers were 1.311, 1.221, 1.146, 1.092, 1.049, 1.021, 1.006, 1.001, 1.000, 1.000, and 1.000, respectively. Prematurity and postmaturity femoral and tibial lengths of 21 patients were used to assess the prediction accuracy. The mean prediction error was 0 cm, 0.8 cm, and 1.6 cm fbr the multiplier method using our coefficients, Paley＇s coefficients, and Anderson＇s method, respectively. Conclusions： Our coefficients for the multiplier method are reliable in predicting lower limb length growth of Chinese children with osteosarcoma.

Magnetic Resonance Imaging for the Assessment of Long Bone Tumors

Background： Wide resection margins of osseous tumors are associated with a low incidence of local recurrence, making accurate measurement of the intraosseous extent of primary malignant long bone tumors is crucial. We compared the intraosseous tumor extent assessed by magnetic resonance imaging （MRI） with the gross specimen to evaluate the accuracy of MRI. Methods： A total of 255 patients with primary malignant tumors in the long bones were included. Using MRI, we defined the length of tumor as the distance from the articular surface to the boundary between abnormal and normal marrow signal. The extent of the abnormal intraosseous signal was measured on unenhanced T1-weighted （T1WI） magnetic resonance images after chemotherapy. All gross surgical specimens were sectioned, and tumor extent was measured. Wilcoxon signed-rank test was used to test the differences between MRI and gross specimen findings. Spearman＇s correlation analysis was used to test the correlation between groups. Results： Median tumor length by gross specimen （112 mm; range, 45–300 mm） was longer than that by MRI （108 mm; range, 45–304 mm;Z = -6.916, P 〈 0.001）. Of 255 images, tumor length was accurately represented on 27 T1WI magnetic resonance images, overestimated on 79 images, and underestimated on 149 images. The median difference between imaging and gross specimen measurements was 2.0 mm （range： 1.0–15.0 mm） for the 79 cases where tumor length was overestimated, and 5.0 mm （range： 1.0–18.0 mm） for the 149 cases where tumor length was underestimated. The Spearman correlation demonstrated a high correlation of tumor length on gross specimen with the tumor length on MRI （R = 0.99, P 〈 0.01）. Conclusions： We conclude that preoperative MRI could be a useful method in determining intramedullary malignant bone tumor boundaries and may serve as an accepted assessment method of long bone tumors before limb-sparing surgery.

The Surgical Treatment and Outcome of Nonmetastatic Extremity Osteosarcoma with Pathological Fractures

Background：Recent studies have suggested that the presence of a pathological fracture does not impact on oncologic outcomes and the feasibility of limb salvage surgery （LSS） in appropriately selected patients when combined with neoadjuvant chemotherapy.These have largely been single institutional studies with limited numbers.The Eastern Asian Musculoskeletal Oncology Group reviewed the data from three large volume Asian orthopedic oncology centers to determine whether the presence of a pathologic fracture affected outcomes in osteosarcoma patients.Methods：A retrospective review of the data was conducted.Ninety-five cases ofnonmetastatic extremity osteosarcoma with a pathological fracture and 887 cases without fracture treated during the same period were compared.Results：In the fracture group,the LSS rate was 62.1％,and the rate of amputation was 37.9％.In the nonfracture group,the LSS rate was 74.7％,and the amputation was 25.3％.In patients with a pathologic fracture,the rate of local recurrence for LSS and amputation groups was 8.5％ and 2.8％,respectively.In this group,the 5-year survival in the LSS group was 66％ as against.46.8％ in the amputation group.Conclusions：Our study suggests that surgically treated patients with pathologic fractures in osteosarcoma have adequate local control and do not have a poorer outcome compared to patients without a fracture.Though osteosarcoma with a pathologic fracture is not a contraindication for limb salvage,appropriate case selection is important when deciding local control options to ensure adequate oncologic clearance.

Transition from Tumor Tissue to Bone Marrow in Patients with Appendicular Osteosarcoma after Neoadjuvant Chemotherapy

Background：Limb-salvage surgery is the standard procedure for the treatment of appendicular osteosarcoma.Precise resection is the trend in limb-salvage surgery.The aim of this study was to evaluate a large series of cases to identify the histological relationship between the tumor and marrow and determine the intramedullary transition type and width from the tumor to normal marrow in patients with osteosarcoma after neoadjuvant chemotherapy.Methods：One hundred and six osteosarcoma specimens were evaluated.The tissue specimens were sectioned through the coronal axis by an electronic saw.The tissue was immersed in formalin solution for fixation and subsequently decalcified.The interface between the tumor and normal bone marrow was grossly determined and submitted for microscopic evaluation to detect the relationship between the tumor and bone marrow and identify the transition type and width.All histological slides were examined by experienced orthopedic pathologists.Results：Histologically,the interface between the tumor and normal bone marrow was classified into two patterns：＂clear＂ and ＂infiltrated.＂The clear pattern,characterized by a clear boundary between the tumor and marrow,was identified in sixty cases （56.6%）.A subtype of the clear type,characterized by fibrous bands between the tumor and marrow,was found in 13 cases （12.3%）.The infiltrated pattern,characterized by a boundary with tumor cell clusters embedded in the marrow,was found in 46 cases （43.4%）.The infiltrating depth varied from 1 to 4 mm （mean,2.6 ＋ 0.7 mm）.No tumor cells were observed in the normal bone marrow areas next to the interface.Conclusions：The transition from osteosarcoma tissue to bone marrow after neoadjuvant chemotherapy can be divided into two histological patterns：clear and infiltrated.The greatest infiltration width was 4 mm from tumor to normal marrow in this study.This depth should be considered in the presurgical plan.

Surface Patterns of a Tetrahedral Polyelectrolyte Brush Induced by Grafting Density and Charge Fraction

A tetrahedral polyelectrolyte brush in the presence of trivalent counterions is researched under the condition of good solution by mea ns of molecular dynamics simulati ons.Grafting density and charge fraction are varied to gen erate a series of surface patter ns.Lateral microphase separation happens and various interesting pinned patches appear at appropriate charge fraction and grafting density.Through a careful analysis on the brush thickness,the pair correlation functions,the distributions of net charge,and the four states of trivalent counterions in the brush,we find that the ordered surface patterns and special properties are induced by the pure electrostatic correlation effect of trivalent ions even in the good solvent.Furthermore,the dependences of electrostatic correlation on the charge fraction of tethered chains are evaluated for fixed grafting den sity.Also,our results can serve as a guide for precise control over the stimuli-responsive materials rational and self-assembly of nanoparticles.

Biomechanical Properties of Synthetic Mesh Reconstructed Glenohumeral Joint Capsule

Synthetic mesh is often used in soft tissue reconstruction after artificial prosthesis replacement for patients with proximal humeral bone tumors.We carried out biomechanical and histological tests on two amputated extremities to test the stability of the joint and the biocompatibility of the synthetic meshes.