In this study, we evaluated the bone regenerative capability of a customizable hydroxyapatite (HA) and tricalcium phosphate (TCP) scaffold using a digital light processing (DLP)-type 3D printing system. Twelve healthy adult male beagle dogs were the study subjects. A total of 48 defects were created, with two defects on each side of the mandible in all the dogs. The defect sites in the negative control group (sixteen defects) were left untreated (the NS group), whereas those in the positive control group (sixteen defects) were filled with a particle-type substitute (the PS group). The defect sites in the experimental groups (sixteen defects) were filled with a 3D printed substitute (the 3DS group). Six dogs each were exterminated after healing periods of 4 and 8 weeks. Radiological and histomorphometrical evaluations were then performed. None of the groups showed any specific problems. In radiological evaluation, there was a significant difference in the amount of new bone formation after 4 weeks (p < 0.05) between the PS and 3DS groups. For both of the evaluations, the difference in the total amount of bone after 8 weeks was statistically significant (p < 0.05). There was no statistically significant difference in new bone between the PS and 3DS groups in both evaluations after 8 weeks (p > 0.05). The proposed HA/TCP scaffold without polymers, obtained using the DLP-type 3D printing system, can be applied for bone regeneration. The 3D printing of a HA/TCP scaffold without polymers can be used for fabricating customized bone grafting substitutes.

Reduced expression of SET7/9, a histone mono-methyltransferase, is associated with gastric cancer progression

This study evaluated the mechanical properties and bone regeneration ability of 3D-printed pure hydroxyapatite (HA)/tricalcium phosphate (TCP) pure ceramic scaffolds with variable pore architectures. A digital light processing (DLP) 3D printer was used to construct block-type scaffolds containing only HA and TCP after the polymer binder was completely removed by heat treatment. The compressive strength and porosity of the blocks with various structures were measured; scaffolds with different pore sizes were implanted in rabbit calvarial models. The animals were observed for eight weeks, and six animals were euthanized in the fourth and eighth weeks. Then, the specimens were evaluated using radiological and histological analyses. Larger scaffold pore sizes resulted in enhanced bone formation after four weeks (p < 0.05). However, in the eighth week, a correlation between pore size and bone formation was not observed (p > 0.05). The findings showed that various pore architectures of HA/TCP scaffolds can be achieved using DLP 3D printing, which can be a valuable tool for optimizing bone-scaffold properties for specific clinical treatments. As the pore size only influenced bone regeneration in the initial stage, further studies are required for pore-size optimization to balance the initial bone regeneration and mechanical strength of the scaffold.

Sacrococcygeal teratomas are the most common solid tumor in newborn infants. The diagnosis is not difficult in many cases; however, there should be additional information on imaging studies in order to manage those infants properly. Details include histology, morphologic classification, complications such as rupture, bleeding, and mass effects on the adjacent structures. Although imaging features cannot accurately predict the histologic subtypes of the tumors, thorough evaluation of the imaging features can help distinguish malignant tumors from benign tumors. In this article, pathogenesis, histological characteristics, clinical considerations, and morphologic characteristics will be discussed.

This study was designed to evaluate 4 new cases of papillary glioneuronal tumors (PGNTs), 2 of which had atypical histologic features, provides extensive IHC characterization, performed comparative genomic hybridization in 2 of our cases, and reviews the recent literature. The study group comprised 3 women and 1 man, with ages ranging from 12 to 75 years. Patients presented with seizures (n=3) or muscle spasm (n=1), and the tumors were located in the supratentorial region of the brain (3 in the frontal and 1 in the parietotemporal lobe). The 2 atypical tumors showed a moderately high mitotic rate (4 and 7/10 HPF, each), vascular endothelial hyperplasia, and necrosis. Tumor cells expressed both neuronal and glial markers, but the degree of neuronal versus glial expression was varied. None of the tumors expressed p53, EGFR wild type/vIII, IDH1, or CD34; however, nestin, galectin-3, and S100 were positive in the tumor cells. No EGFR gene amplification or 1p/19q deletion was found by fluorescence in situ hybridization. Half of the cases revealed PTEN loss by immunohistochemistry, and MGMT methylation was positive in 3 cases by MGMT methylation-specific polymerase chain reaction. Ultrastructurally, either astrocytic or neuronal differentiation was observed, but we could not identify any hybrid cells. An array-based comparative genomic hybridization study revealed loss of 1q, 6p, 8p, 9p, 9q, and 16q and gain of 2q, 3p, 5q, 6p, 7q, 10q, 16q, 19p, and 22q in 2 cases simultaneously. The first patient, who underwent subtotal resection, died because of progression of the tumor within 9 months after surgery; however, 2 patients were symptom free and progression free at 34 and 48 months after gross total resection (the patient 2: plus radiotherapy, the patient 3: no adjuvant chemo- or radiotherapy). The last patient developed seizures after a long symptom-free period (40 mo) with no evidence of tumor recurrence. Our 4 new cases, in conjunction with the literature review, reinforce that PGNTs are tumors that usually occur in young adults (mean age, 24 y); they are most often cystic with a mural nodule or are cystic/solid, supratentorial, closely located with the ventricle, molecularly genetically different from astrocytic or oligodendroglial tumors, and indolent in behavior. Cases (2 of 4 in our study) with atypical histologic features or that occur in advanced age (75 y), and sporadic reports of histologically or biologically aggressive PGNTs, serve to remind pathologists that the full spectrum of PGNTs is as yet unknown.

Background: The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. Methods: We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. Results: PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. “Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8^+/low tumor-infiltrating lymphocytes (TILs),” and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3^+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3^+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines. Conclusions: The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of “tumoral PD-L1/immune cell PD-L1/CD8⁺ TILs” may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8^+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.