Development and validation of a preoperative nomogram for predicting positive surgical margins after laparoscopic radical prostatectomy.

BACKGROUND: Positive surgical margins are independent risk factor for biochemical recurrence, local recurrence, and distant metastasis after radical prostatectomy. However, limited predictive tools are available. This study aimed to develop and validate a preoperative nomogram for predicting positive surgical margins after laparoscopic radical prostatectomy (LRP). METHODS: From January 2010 to March 2016, a total of 418 patients who underwent LRP without receiving neoadjuvant therapy at Peking University Third Hospital were retrospectively involved in this study. Clinical and pathological results of each patient were collected for further analysis. Univariable and multivariable logistic regression (backward stepwise method) were used for the nomogram development. The concordance index (CI), calibration curve analysis and decision curve analysis were used to evaluate the performance of our model. RESULTS: Of 418 patients involved in this study, 142 patients (34.0%) had a positive surgical margin on final pathology. Based on the backward selection, four variables were included in the final multivariable regression model, including the percentage of positive cores in preoperative biopsy, clinical stage, free prostate specific antigen (fPSA)/total PSA (tPSA), and age. A nomogram was developed using these four variables. The concordance index (C-index) of the nomogram was 0.722 in the development cohort and 0.700 in the bootstrap validations. The bias-corrected calibration plot showed a limited departure from the ideal line with a mean absolute error of 2.0%. In decision curve analyses, the nomogram showed net benefits in the range from 0.2 to 0.7. CONCLUSION: A nomogram to predict positive surgical margins after LRP was developed and validated, which could help urologists plan surgical procedures.

[Variations in expressions of periostin and related factors in early stage of wound healing and scar remodeling in rats].

OBJECTIVE: To investigate the expressions of periostin (PN), angiopoietin-1 (Ang-1), vascular epithelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1) during the processes of scar formation and modulation in rat cutaneous wounds and probe into their roles in wound healing and scaring. METHODS: Eighty-two male Sprague-Dawley (SD) rats were randomly divided into 10 groups with 8-9 rats in each group. Two 2 cm×2 cm full-thickness excisional wounds in the back were created in each rat. The wound surface was observed, and the healing area was measured. The pathological change was observed after hematoxylin and eosin (HE) staining. The expressions of PN, Ang-1, VEGF and Flk-1 in wound surface scar at 4-8 weeks were determined with immunohistochemistry. The expressions of PN, Ang-1 and VEGF were determined by Western blotting. The normal skin was served as control. RESULTS: HE staining showed that the wound surface tissue had healed with epithelization at 4-8 weeks. Immunohistochemistry results showed that there was no significant difference in Flk-1 expression between wound surface tissue and normal skin. The PN expression (A value/µm(2)) in wound surface tissue was significantly lower than that in normal skin at 5 weeks (2.43±0.44 vs. 4.24±0.50, P<0.05), and the expression of Ang-1 and VEGF (A value/µm(2)) at 4, 5, 6, 8 weeks was significantly lower than that in normal skin (Ang-1: 3.51±0.93, 3.10±0.57, 2.77±0.59, 2.77±1.26 vs. 4.89±0.48; VEGF: 1.76±0.68, 1.75±0.49, 1.99±0.42, 1.94±0.86 vs. 4.86±1.63, all P<0.05). In wound surface scar, PN and Flk-1 positive signal was found in cell, and the Ang-1 and VEGF positive signal in extracellular matrix. Western blotting data demonstrated that the expressions of PN, Ang-1 and VEGF peaked at the 10th day after excision with increases to 7.90-22.56 folds compared with normal skin (PN: 2.45±1.51 vs. 0.31±0.19, Ang-1: 18.43±15.20 vs. 1.53±1.42, VEGF: 6.09±4.66 vs. 0.27±0.13, P<0.05 or P<0.01), and then followed with a decrease. CONCLUSIONS: PN, Ang-1, VEGF and Flk-1 are transiently overexpressed in early stage of full-thickness cutaneous wound healing in rats. Their expressions vary in wounds and scars. They participate in the healing of full-thickness cutaneous wounds together and may be essential for the proliferation stage during wound healing.

[The expressions of periostin and the related factors during healing process of full-thickness cutaneous wound in rat].

OBJECTIVE: To observe the expression of osteoblast-specific factor 2 (periostin, PN), angiopoietin-1 (Ang-1), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 [VEGFR-2/fetal liver kinase-1 (FLK-1)] in wound surface and its peripheral skin, and their effects on wound healing in rats. METHODS: Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups, with 8 rats in each group. An area of 2 cm×2 cm full-thickness skin was excised on both sides of the back of rats. Specimens from wounds were obtained on 1, 4, 7, 10, 14, 21 days after operation, and histological evaluation and immunohistochemical staining of PN, Ang-1, VEGF and FLK-1 were made to determine their expression levels. Normal skin specimens were obtained as normal controls. RESULTS: The expressions of PN, Ang-1, VEGF and FLK-1 were significantly increased in wound surface after operation. Compared with the skin of normal controls, the expression of PN in the tissues of wound increased by 234.4% on the 1st day, and then increased continuously up to 597.9% on the 7th day (reaching the peak) after operation, followed by a decrease, the increase rate was 280.9% on the 21st day, and still remained at a high level (all P < 0.05). The expression of Ang-1 in the tissue of wound increased by 128.1% on the 1st day and 327.5% on the 4th day (reaching the peak), and then, it was gradually decreased. The increase rate was only 80.5% on the 14th day and it rose slightly later (all P < 0.05). The expression of VEGF in the tissues of wound reached the peak (165.8%) on the 7th day. Then it decreased with a slight fluctuation (all P < 0.05). The expression of FLK-1 in the tissues of wound was increased by 56.1% on the 1st day, and the level remained. It reached the peak by an increase of 70.1% on the 7th day (both P < 0.05). Then, it was lowered after the 10th day (all P > 0.05). CONCLUSIONS: The expressions of PN, Ang-1, VEGF, FLK-1 were obviously increased during healing of skin wound, with different peaking time and expressing rates. The increase in expression of PN showed the longest duration and highest peak value. The PN, Ang-1, VEGF, FLK-1 all play a role in the wound healing process, and PN might play an important role during the healing process of a full-thickness cutaneous wound.

[Literature mining and bioinformatic analysis of dysregulated genes in hypertrophic scar].

OBJECTIVE: To explore the pathogenesis mechanism of hypertrophic scar (HS) and the effective means for its clinical treatment, the difference of the gene expressions between HS and normal skin was compared. METHODS: The differentially expressed genes between HS and normal skin were obtained by mining PubMed. The dysregulated genes in HS were analyzed by a series of bioinformatics methods, including protein-protein interaction networks, pathways, Gene Ontology and functional annotation clustering analysis. RESULTS: A total of 55 dysregulated genes in HS was identified (46 up-regulated genes and 9 down-regulated genes). Fifty-one genes were found to encode proteins with interaction network, including up-regulated genes TGFB1, FN1, JUN, COL1A1, CTGF, VEGFA, FOS, COL3A1, IGF1, IL4, PELO, SMAD2, TIMP1, PCNA, and ITGA4 and down-regulated genes ITGB1 and DCN as the central nodes for this network. The dysregulated genes in HS involved in a variety of biological pathways, such as focal adhesion formation, integrin signal transduction, and tumor formation. Furthermore, the dysregulated genes in HS played the important roles in biological processes of cell surface receptor linked signal transduction, tissue development, cell proliferation and apoptosis, and macromolecule biosynthetic process, as well as in molecular function of calcium ion binding, double-stranded DNA binding, heparin binding, promoter binding and MAP kinase activity. The results of functional annotation clustering analysis revealed that the dysregulated genes in HS involved in epidermis development, angiogenesis, and apoptosis. CONCLUSION: Such key genes as TGFB1, FN1, and JUN, along with the pathways, biological processes and molecular functions involving epidermis development, angiogenesis, and extracellular matrix-integrin-focal adhesion signal transduction may play the important roles in the development of HS. The investigations of the dysregulated genes in HS could provide the new targets for clinical treatment.