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Background: Functional performance as measured by the Karnofsky Performance Status (KPS) scale has been linked to the outcomes of liver transplant patients; however, the effect of KPS on the outcomes of the hepatocellular carcinoma (HCC) liver transplant population has not been fully elucidated. We aimed to investigate the association between pre-transplant KPS score and long-term outcomes in HCC patients listed for liver transplantation. Methods: Adult HCC candidates listed on the Scientific Registry of Transplant Recipients (SRTR) database from January 1, 2011 to December 31, 2017 were grouped into group I (KPS 80–100%, n = 8,379), group II (KPS 50–70%, n = 8,091), and group III (KPS 10–40%, n = 1,256) based on percentage KPS score at listing. Survival was compared and multivariable analysis was performed to identify independent predictors. Results: Patients with low KPS score had a higher risk of removal from the waiting list. The 5-year intent-to-treat survival was 57.7% in group I, 53.2% in group II and 46.7% in group III (P < 0.001). The corresponding overall survival was 77.6%, 73.7% and 66.3% in three groups, respectively (P < 0.001). Multivariable analysis demonstrated that KPS was an independent predictor of intent-to-treat survival (P < 0.001, reference group I; HR 1.19 [95%CI 1.07–1.31] for group II, P = 0.001; HR 1.63 [95%CI 1.34–1.99] for group III, P < 0.001) and overall survival(P < 0.001, reference group I; HR 1.16 [95%CI 1.05–1.28] for group II, P = 0.004; HR 1.53 [95%CI 1.26–1.87] for group III, P < 0.001). The cumulative 5-year recurrence rates was higher in group III patients (7.4%), compared with 5.2% in group I and 5.5% in group II (P = 0.037). However, this was not significant in the competing regression analysis. Conclusions: Low pre-transplant KPS score is associated with inferior long-term survival in liver transplant HCC patients, but is not significantly associated with post-transplant tumor recurrence. [ABSTRACT FROM AUTHOR]

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1–π–A–D2–R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes. [ABSTRACT FROM AUTHOR]

Cerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various radionuclides and radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various fluorescent probes have been combined with radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it's interaction with fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+ doped gadolinium oxide (Gd2O3:Eu) was synthesized and combined with radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and radiopharmaceutical were investigated using 18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and 18F-FDG reached 369 times as high as that of CLI using 18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative tumor imaging. Compared with 18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and 18F-FDG combination achieved a much higher tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24 vs. 1.87 ± 0.73, P = 0.0030). The use of Gd2O3:Eu@PVA and 18F-FDG also assisted intraoperative detection of tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of image-guided surgery demonstrated feasibility of image-guided tumor resection using Gd2O3:Eu@PVA and 18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with 18F-FDG in intraoperative tumor imaging and image-guided tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of tumor and intraoperatively guide tumor resection. [ABSTRACT FROM AUTHOR]

Background: Primary hyperoxaluria (PH) is an inherited disease lacking of hepatic oxalic acid metabolic enzymes which could lead to irreverisible renal damage. Currently, liver-kidney transplantation is a curative but highly invasive therapy used to treat patients with PH. However, limited studies have focused on combined liver-kidney transplantation (CLKT) and sequential liver and kidney transplantation (SLKT) in patients with PH.Methods: The present study included 201 patients with PH who received both liver and kidney transplants and who were listed on the Scientific Registry of Transplant Recipients from 1987 to 2018. According to the liver-kidney transplant procedure, patients were separated into a CLKT group and a SLKT group. Patient demographics and transplant outcomes were assessed in each group.Results: Compared with the SLKT group, The CLKT group got a worse pretransplant dialysis condition in both the proportion of patients under pretransplant dialysis (p = 0.048) and the duration of the pretransplant dialysis (p < 0.001). The SLKT group got higher human leukocyte antigen mismatch score of kidney donor (p < 0.001) and liver donor (p = 0.003). The CLKT group utilized higher proportion (98.9%) of organs from a single deceased donor, while the SLKT group utilized 75.0% of organs from deceased liver donors and only 35.0% of organs from deceased kidney donors (p < 0.001). Kidney function measured by serum creatinine concentration before liver transplantation (LT) or CLKT was similar (p = 0.305) between groups. Patient survival was not significantly different between the two groups (p = 0.717) and liver (p = 0.685) and kidney (p = 0.464) graft outcomes were comparable between the two groups.Conclusions: SLKT seems to be an alternative option with strict condition for CLKT, further exploration about the SLKT is still required. [ABSTRACT FROM AUTHOR]

Background: The ubiquitin-proteasome system and macroautophagy (hereafter referred to autophagy) are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy. Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired. Method: Autophagy activation was measured using acridine orange staining and LC3 transition. Cell viability and apoptosis were measured using MTT assay and flow cytometry, respectively. Beclin 1 expression vectors or shRNA against Beclin 1 (shBeclin 1) were transfected to investigate the role of Beclin 1 in autophagy activation and cytotoxicity of ovarian cancer cells induced by proteasome inhibitors. Results: Proteasome inhibitors suppressed proliferation and induced autophagy in ovarian cancer cells. Neither phosphoinositide 3-kinase (PI3K) inhibitors nor shRNA against Beclin 1 could abolish the formation of acidic vacuoles and the processing of LC3 induced by proteasome inhibitors. Moreover, Beclin 1 overexpression enhanced anti-proliferative effects of proteasome inhibitors in ovarian cancer cells. Conclusions: For the first time, the current study demonstrated that proteasome inhibitors induced PI3K and Beclin 1-independent autophagy in ovarian cancer cells. In addition, this study revealed autophagy-independent tumor suppressive effects of Beclin 1 in ovarian cancer cells. [ABSTRACT FROM AUTHOR]