Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.
Abstract Background The influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC. Methods We retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease‐free survival (DFS), surgery‐related outcomes, and surgical approaches were collected. Results A total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT ( p < 0.001). There was no significance in OS ( p = 0.790), DFS ( p = 0.580), and surgery‐related outcomes (all p > 0.05) between both groups. Decreased referrals ( p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation ( p = 0.004) were all associated with better OS, while fewer positive LNs ( p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery‐related outcomes between different TTT groups of incidental GBC patients (all p > 0.05). Conclusions Positive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery‐related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.
The primary laparoscopic approach (PLA) for T1b/T2 gallbladder cancer (GBC) remains contradicted. We aimed to compare the perioperative and long-term outcomes after PLA versus open approach (OA) for T1b/T2 GBC.Patients with resected T1b/T2 GBC were selected from our hospital between January 2011 and August 2018. Overall survival (OS), disease-free survival (DFS), and several secondary outcomes were used to evaluate safety and effectiveness. Subgroup analyses were performed to identify significant risk factors for OS/DFS in GBC patients undergoing PLA/OA.A total of 114 patients who underwent OA (n = 61) or PLA (n = 53) were included in the study. The percent of PLA cases was increased over time from 40.0% in 2011 to 70.0% in 2018 (p < 0.05). There was no significant difference in OS [hazard ratio (HR), 1.572; 95% confidence interval (CI), 0.866-2.855; p = 0.13] and DFS (HR, 1.225; 95% CI, 0.677-2.218; p = 0.49). No significance was found for intraoperative drainage placement (p = 0.253), intraoperative blood loss (p = 0.497), operation time (p = 0.105), postoperative hospitalization (p = 0.797), positive LNs (p = 0.494), total harvested LNs (p = 0.067), and recurrence rates (P = 0.334). Subgroup analyses demonstrated no significance of conversion rates after PLA (all p > 0.05). Patients undergoing PLA with good/poor OS would have similar recurrence rates (p = 0.402). Positive LNs (p = 0.032) and tumor differentiation (p = 0.048) were identified as risk factors for OS after PLA, while positive LNs (p = 0.005) was identified for OS after OA. Moreover, age (p = 0.013), gallbladder stone (p = 0.008), tumor size (p = 0.028), and positive LNs (p = 0.044) were potential risk factors for DFS after OA.PLA for T1b/T2 GBC was comparable to OA in terms of perioperative and long-term outcomes. Less positive LNs and well-differentiated tumors were independent predictors for better OS after PLA, and less positive LNs were also identified for better OS after OA. Additionally, younger age, without gallbladder stone, smaller tumor size, and less positive LNs were potential risk factors for better DFS after OA.
BACKGROUNDPostoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC).However, the prognostic and predictive factors remain unclear. AIMTo assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC. METHODSUnivariate and multivariate analyses were performed to identify the potential prognostic factors for OS.In order to assess the predictive factors of PA-TACE benefit, the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model. RESULTSA total of 378 patients (PA-TACE vs surgery alone, 189:189) from three centers
Exposure of the hepatic artery is a fundamental step in many surgeries, during which iatrogenic hepatic artery injury may occur. Although the incidence of hepatic artery haemorrhage is low, its occurrence can lead to life-threatening haemorrhage. It is difficult and dangerous to accumulate clinical experience in laparoscopic hepatic artery repair in actual patients, and simulation training models for laparoscopic hepatic artery repair are currently lacking. In this study, a 3D printed model was designed to simulate the training curriculum for sudden hepatic artery haemorrhage, but whether training with the 3D printed model could yield superior skill improvement for surgeons remained to be determined.
Aim: To determine if PD-L1 can be used as a biomarker to predict the efficacy of anti-PD-1/PD-L1 inhibitors in hepatocellular carcinoma (HCC). Methods: Relevant studies from a specific search of the four databases from October 2014 to December 2022 were included in this meta-analysis. Results: Higher PD-L1 expression levels were associated with a higher objective response rate (ORR). Higher PD-L1 expression levels on tumor cells and tumor proportion score were associated with higher ORR. PD-L1 was capable of predicting the effectiveness of nivolumab. Dako 28-8 is a promising assay for HCC. Conclusion: PD-L1 is a predictive biomarker for ORR in HCC. Tumor proportion score and PD-L1 expression levels on tumor cells are potential scoring algorithms.Clinically, liver cancer patients with high PD-L1 levels may not benefit from immunotherapy. Conversely, some patients with low PD-L1 level can benefit from it. Therefore, the concept of PD-L1 as a predictive indicator in liver cancer is defective. Whether PD-L1 can serve as an indicator in liver cancer patients receiving immunotherapy needs urgent confirmation. In this work, we evaluated the feasibility of PD-L1 as a prognostic biomarker for immunotherapy. The results suggested that high expression of PD-L1 by tumor cells rather than tumor tissue was correlated with better prognosis.
Background: The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. Objective: To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. Methods: A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model’s performance. Results: The final CR model consisted of 5 independent predictors, including TPR-signature (p < 0.001), AFP (p = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification (p = 0.01), tumor location (p = 0.039), and arterial hyperenhancement (p = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60–3.69; p < 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. Conclusions: The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE.
Accumulating evidence has shown many similarities and differences of gene profiles and pathways between pediatric and adult ulcerative colitis (UC) patients. In this study, we aimed to investigate the shared genes and pathways in intestinal tissues of pediatric and adult UC. Differentially expressed genes (DEGs) between pediatric and adult UC were identified via bioinformatic analysis of Gene Expression Omnibus datasets GSE87473 and GSE126124. Gene Ontology and pathway enrichment were used to analyze overlapped and distinguished DEGs. Gene Set Variation Analysis (GSVA) was utilized for contrast consistency. Mice colitis models were induced by dextran sulfate sodium (DSS) and Citrobacter rodentium. 2616 DEGs were screened out in intestinal tissues of adult UC compared with those of adult healthy controls, and 1195 DEGs in pediatrics. Same pathways between pediatric and adult UC were enriched using overlapped DEGs, mainly related to immune responses and metabolic processes, including butyrate metabolism, which was also identified by GSVA analysis. Of note, butyrate metabolism was the exclusive down-regulated pathway enriched by these two analyses, indicating that butyrate metabolism is one of the key pathways associated with both pediatric and adult UC. In addition, butyrate suppressed DSS-induced and Citrobacter rodentium-induced intestinal inflammation in mice. Therefore, the study revealed that butyrate metabolism was critical in both pediatric and adult UC. And butyrate suppressed colitis in mice, which provided a theoretical basis for the potential treatment of butyrate for UC patients. Abbreviations: UC, Ulcerative colitis; IBD, Inflammatory bowel disease; DEGs, Differentially expressed genes; GEO, Gene Expression Omnibus; SVA, Spatial variant apodization; LIMMA, Linear models for the microarray data; FC, Fold change; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; GSVA, Gene Set Variation Analysis; MSigDB, Molecular Signatures Database; WT, Wild-type; DSS, Dextran sulfate sodium; HC, Healthy control; SD, Standard deviation; SNHG5, Small nucleolar RNA host gene 5; GLP-2, Glucagon-like peptide 2; GSE, Gene set enrichment; ECM, Extracellular matrix; TCA, Tricarboxylic acid cycle; NA, Not available.
There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC). We hypothesized that the laparoscopic approach is an alternative for early GBC.To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early GBC.A comprehensive search of online databases, including MEDLINE (PubMed), Cochrane libraries, and Web of Science, was performed to identify non-comparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019. A fixed-effects meta-analysis was performed for 1- and 5-year overall survival and postoperative complications, while 3-year overall survival, operation time, blood loss, the number of lymph node dissected, and postoperative hospital stay were analyzed by random-effects models.The review identified 7 comparative studies and 8 non-comparative studies. 1068 patients (laparoscopic surgery: 613; open surgery: 455) were included in the meta-analysis of 1-, 3-, and 5-year overall survival with no significant differences observed [(HR = 0.54; 95%CI: 0.29-1.00; I2 = 0.0%; P = 0.051), (HR = 0.75; 95%CI: 0.34-1.65; I2 = 60.7%; P = 0.474), (HR = 0.71; 95%CI: 0.47-1.08; I2 = 49.6%; P = 0.107), respectively]. There were no significant differences in operation time [weighted mean difference (WMD) = 18.69; 95%CI: -19.98-57.36; I2 = 81.4%; P = 0.343], intraoperative blood loss (WMD = -169.14; 95%CI: -377.86-39.57; I2 = 89.5%; P = 0.112), the number of lymph nodes resected (WMD = 0.12; 95%CI: -2.95-3.18; I2 = 73.4%; P = 0.940), and the complication rate (OR = 0.69; 95%CI: 0.30-1.58; I2 = 0.0%; P = 0.377 ) between the two groups, while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD = -5.09; 95%CI: -8.74- -1.45; I2 = 91.0%; P= 0.006).This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open surgery with comparable survival and operation-related outcomes for early GBC.
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