A Novel Prognostic Nomogram for Patients With Recurrence of Intrahepatic Cholangiocarcinoma After Initial Surgery.

Background: The prognosis of patients with post-operative recurrent intrahepatic cholangiocarcinoma (ICC) is at great variance. We aimed to propose a novel efficient prognostic nomogram in facilitating the risk stratification for post-operative recurrent ICC patients. Methods: From 2000 to 2016, a total of 237 post-operative recurrent ICC patients were enrolled in this study, and randomly divided into training (n = 178) and validation cohorts (n = 59) at a ratio of 3:1. The performance of this nomogram was assessed by discrimination, calibration, and clinical usefulness, and the results were compared with four other currently used ICC staging systems. Results: On multivariate analysis of the training cohort, serum CA 19-9, albumin-bilirubin grade at recurrence, time from primary resection to recurrence, tumor number at recurrence, and treatment for recurrence were selected for the model. The concordance index (C-index) of our model was 0.791 [95% confidence interval (CI), 0.736-0.846], which was statistically higher than the values of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (0.610), Liver Cancer Study Group of Japan (0.613), Nathan (0.582), and Okabayashi (0.600; P < 0.001 for all). The nomogram performed well in terms of calibration when compared with actual observation. The findings were supported by the validation cohort. Conclusions: Compared with four currently used staging systems for ICC, our nomogram showed more promising clinical utility in improving individualized predictions of survival for post-operative recurrent ICC patients.

The impact of surgery in metastatic pancreatic neuroendocrine tumors: a competing risk analysis.

Aim The role of surgery in the treatment of metastatic pancreatic neuroendocrine tumors (PNETs) was controversial. The objectives of this study were to illustrate the impact of surgery in improving the prognosis of patients with metastatic PNETs and build nomograms to predict overall survival (OS) and cancer-specific survival (CSS) based on a large population-based cohort. Methods Patients diagnosed with metastatic PNETs between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Nomograms for estimating OS and CSS were established based on Cox regression model and Fine and Grey's model. The precision of the nomograms was evaluated and compared using concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). Results The study cohort included 1966 patients with metastatic PNETs. It was shown that the surgery provided survival benefit for all groups of patients with metastatic PNETs. In the whole study cohort, 1-, 2- and 3-year OS and CSS were 51.5, 37.1 and 29.4% and 53.0, 38.9 and 31.1%, respectively. The established nomograms were well calibrated, and had good discriminative ability, with C-indexes of 0.773 for OS prediction and 0.774 for CSS prediction. Conclusions Patients with metastatic PNETs could benefit from surgery when the surgery tolerance was acceptable. The established nomograms could stratify patients who were categorized as tumor-node-metastasis (TNM) IV stage into groups with diverse prognoses, showing better discrimination and calibration of the established nomograms, compared with 8th TNM stage system in predicting OS and CSS for patients with metastatic PNETs.

Transarterial chemoembolization combined with recombinant human adenovirus type 5 H101 prolongs overall survival of patients with intermediate to advanced hepatocellular carcinoma: a prognostic nomogram study.

BACKGROUND: Patients with intermediate to advanced hepatocellular carcinoma (HCC) are most commonly treated with transarterial chemoembolization (TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5 (H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an effective nomogram for predicting individual survival outcomes of these patients. METHODS: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat-sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101 (TACE with H101 group) and 238 patients who received TACE without H101 (TACE group) were analyzed. Overall survival (OS) was evaluated using the Kaplan-Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index (c-index) and calibration plots. RESULTS: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group (1-year OS rate, 53.8% vs. 61.3%; 2-year OS rate, 33.4% vs. 44.2%; 3-year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha-fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted survival and observed survival. The c-index of the nomogram for predicting OS was 0.716 (95% confidence interval 0.686-0.746). CONCLUSIONS: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.

Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101.

BACKGROUND: The systemic inflammatory response plays an important role in cancer development and progression. An original inflammation-based staging system for predicting survival in patients undergoing transarterial chemoembolization (TACE) combined with recombinant human type-5 adenovirus H101 is not available. This study aimed to validate the prognostic value of inflammation scores for patients with hepatocellular carcinoma (HCC) who were treated with TACE combined with H101. METHODS: The data from 216 patients with HCC who underwent TACE combined with H101 from January 2007 to July 2015 were retrospectively collected, and the association of the inflammation scores with overall survival (OS) was analyzed. Univariate and multivariate analyses were performed to identify variables associated with OS. The prognostic value of the inflammation scores, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil/ platelet-to-lymphocyte ratio (NLR-PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), prognostic index (PI), tumor-node-metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) staging systems were analyzed and compared using the areas under the receiver operating characteristic curves (AUROCs). RESULTS: The estimated 1-, 2-, and 3-year OS rates were 61.3%, 44.2%, and 40.5% for the entire study cohort, respectively; the median OS was 17 months. According to the multivariate Cox proportional hazards model, the pretreatment NLR, tumor diameter and pretreatment alpha-fetoprotein (AFP) levels were independent predictors of OS. The CLIP score had superior discriminative abilities compared with other staging systems, and the NLR-PLR score consistently displayed a higher AUROC value than the other inflammation-based prognostic scores. The combination of the NLR-PLR and CLIP scores exhibited a superior prognostic ability for OS compared to the NLR-PLR or CLIP scores alone. CONCLUSIONS: The NLR-PLR score is a more powerful predictive system than the other inflammation-based scores for patients with HCC who were treated with TACE and H101. The predictive ability may be improved by utilizing a combination of the NLR-PLR and CLIP scores.

Nanocomposites for bone tissue regeneration.

Natural bone tissue possesses a nanocomposite structure that provides appropriate physical and biological properties. For bone tissue regeneration, it is crucial for the biomaterial to mimic living bone tissue. Since no single type of material is able to mimic the composition, structure and properties of native bone, nanocomposites are the best choice for bone tissue regeneration as they can provide the appropriate matrix environment, integrate desirable biological properties, and provide controlled, sequential delivery of multiple growth factors for the different stages of bone tissue regeneration. This article reviews the composition, structure and properties of advanced nanocomposites for bone tissue regeneration. It covers aspects of interest such as the biomimetic synthesis of bone-like nanocomposites, guided bone regeneration from inert biomaterials and bioactive nanocomposites, and nanocomposite scaffolds for bone tissue regeneration. The design, fabrication, and in vitro and in vivo characterization of such nanocomposites are reviewed.

Enhanced ordering in gold nanoparticles self-assembly through excess free ligands.

Self-assembly of nanometer-sized particles is an elegant and economical approach to achieve dense patterns over large areas beyond the resolution and throughput capabilities of electron-beam lithography. In this paper, we present results of self-assembly of oleylamine-capped gold nanoparticles with 8.0 ± 0.3 nm diameter into densely packed and well-ordered monolayers with center-to-center distance of ∼11 nm. Self-assembly was done in a Langmuir-Blodgett trough and picked up onto Si substrates. The nanoparticles undesirably assembled within micrometer-sized "droplets" that were organic in nature. However, within these droplets, we observed that the addition of the excess ligand, oleylamine, drastically enhanced the self-assembly of the nanoparticles into monolayers with near-perfect ordering. This approach has the potential use in templated self-assembly of nanoparticles for rearranging poorly ordered assembly into a commensurate prepatterned substrate.

Designing poly[(R)-3-hydroxybutyrate]-based polyurethane block copolymers for electrospun nanofiber scaffolds with improved mechanical properties and enhanced mineralization capability.

Efforts to mineralize electrospun hydrophobic polyester scaffold often require prior surface modification such as plasma or alkaline treatment, which may affect the mechanical integrity of the resultant scaffold. Here through rational design we developed a series of polyurethane block copolymers containing poly[(R)-3-hydroxybutyrate] (PHB) as hard segment and poly(ethylene glycol) (PEG) as soft segment that could be easily fabricated into mineralizable electrospun scaffold without the need of additional surface treatment. To ensure that the block copolymers do not swell excessively in water, PEG content in the polymers was kept below 50 wt %. To obtain good dry and hydrated state mechanical properties with limited PEG, low-molecular-weight PHB-diol with M(n) 1230 and 1790 were used in various molar feed ratios. The macromolecular characteristics of the block copolymers were confirmed by (1)H NMR spectroscopy, gel permeation chromatography (GPC), and thermal gravimetric analyses (TGA). With the incorporation of the hydrophilic PEG segments, the surface and bulk hydrophilicity of the block copolymers were significantly improved. Differential scanning calorimetry (DSC) revealed that the block copolymers had low PHB crystallinity and no PEG crystallinity. This was further confirmed by X-ray diffraction analyses (XRD) in both dry and hydrated states. With short PHB segments and soft PEG coupled together, the block copolymers were no longer brittle. Tensile measurements showed that the block copolymers with higher PEG content or shorter PHB segments were more ductile. Furthermore, their ductility was enhanced in hydrated states with one particular example showing increment in strain at break from 1090 to 1962%. The block copolymers were fabricated into an electrospun fibrous scaffold that was easily mineralized by simple incubation in simulated body fluid. The materials have good potential for bone regeneration application and may be extended to other applications by simply coating them with other biologically active substances.

Effect of molecular orientation on mechanical property of single electrospun fiber of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate].

Electrospun poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] (PHBV) fibers were collected by using a counter electrode collector or a rotating disk collector. The molecular orientation and mechanical property of single PHBV fiber were studied. 2-D wide-angle X-ray diffraction and polarized Fourier transform infrared spectra of the macroscopically aligned fibers confirmed the orientation of polymer chains, with PHBV chains preferentially oriented along the fiber axis. The degree of orientation increased with increasing fiber take-up velocity. X-ray diffraction pattern also indicates the development of beta-form crystal in electrospun PHBV fibers collected at an angular velocity of 1500 rpm. The thermal behavior of electrospun PHBV fibers was studied using modulated differential scanning calorimetry. The tensile properties of single electrospun PHBV fibers were studied using a nanotensile tester. Our results indicate that electrospun PHBV fiber with a higher degree of molecular orientation exhibits a higher tensile modulus and strength but lower strain at break.

Improving hydrophilicity, mechanical properties and biocompatibility of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] through blending with poly[(R)-3-hydroxybutyrate]-alt-poly(ethylene oxide).

Natural source poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] (PHBV) with a low hydroxyvalerate (HV) content ( approximately 8wt.%) was modified by blending it with poly[(R)-3-hydroxybutyrate]-alt-poly(ethylene oxide) (HE) alternating block copolymer. We hypothesized that the adjoining PHB segments could improve the miscibility of the poly(ethylene oxide) segments of HE with the PHBV matrix and therefore improve the physical properties of the PHBV/HE blends. A differential scanning calorimetry study revealed the improved miscibility of PEO segments of HE characterized by the interference of the crystallization of PHBV. The decrease in water contact angle and the increase in equilibrium water uptake of the PHBV/HE blends indicated that both the surface and bulk hydrophilicity of PHBV could be improved through blending HE. The mechanical properties of the hydrated PHBV/HE blends were assessed by measuring their tensile strength. In contrast to the hydrated natural source PHBV, which failed in a brittle manner, the hydrated PHBV/HE blends were ductile. Their strain at break increased with increasing HE content, reaching a maximum of 394% at an HE content of 15wt.%. The excellent integrity of the PHBV/HE blends in water is attributed to the strong affinity between the PHB segments of HE and the PHBV matrix. Platelet adhesion on the film surface of the PHBV/HE blends was investigated in vitro to evaluate their blood compatibility. The results demonstrated that the PHBV/HE blends effectively resisted the adhesion of platelets due to the anchored PEO segments from HE on the film surface.