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BackgroundThe therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in bladder cancer varies among individuals. Identifying reliable predictors of response to these therapies is crucial for optimizing patient outcomes.MethodsThis retrospective study analyzed 348 bladder cancer patients treated with ICIs, with additional validation using data from 248 patients at our institution who underwent PD-L1 immunohistochemical staining. We examined patient smoking history, clinicopathological characteristics, and immune phenotypes. The main focus was the correlation between smoking history and immunotherapy outcomes. Multivariate logistic and Cox proportional hazard regressions were used to adjust for confounders.ResultsThe study cohort comprised 348 bladder cancer patients receiving ICIs. Among them, 116 (33.3%) were never smokers, 197 (56.6%) were former smokers (median pack-years = 28), and 35 (10.1%) were current smokers (median pack-years = 40). Analysis revealed no statistically significant difference in overall survival across different smoking statuses (objective response rates were 11.4% for current smokers, 17.2% for never smokers, and 22.3% for former smokers; P = 0.142, 0.410, and 0.281, respectively). However, a notable trend indicated a potentially better response to immunotherapy in former smokers compared to current and never smokers. In the validation cohort of 248 patients from our institution, immunohistochemical analysis showed that PD-L1 expression was significantly higher in former smokers (55%) compared to current smokers (37%) and never smokers (47%). This observation underscores the potential influence of smoking history on the tumor microenvironment and its responsiveness to ICIs.ConclusionIn conclusion, our study demonstrates the importance of incorporating smoking history in predicting the response to immunotherapy in bladder cancer patients, highlighting its role in personalized cancer treatment approaches. Further research is suggested to explore the comprehensive impact of lifestyle factors on treatment outcomes.

Background: The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients. Methods: The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The “X-Tile” program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively. Results: A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using X-tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (＞8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, P

BackgroundNeoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) remains the cornerstone of treatment for muscle-invasive bladder cancer (MIBC). While platinum-based regimens have demonstrated benefits in tumor downstaging and improved long-term survival for selected patients, they may pose risks for those who are ineligible or unresponsive to chemotherapy.ObjectiveWe undertook a bibliometric analysis to elucidate the breadth of literature on NAC in bladder cancer, discern research trajectories, and underscore emerging avenues of investigation.MethodsA systematic search of the Web of Science Core Collection (WoSCC) was conducted to identify articles pertaining to NAC in bladder cancer from 1999 to 2022. Advanced bibliometric tools, such as VOSviewer, CiteSpace, and SCImago Graphica, facilitated the examination and depicted the publication trends, geographic contributions, institutional affiliations, journal prominence, author collaborations, and salient keywords, emphasizing the top 25 citation bursts.ResultsOur analysis included 1836 publications spanning 1999 to 2022, indicating a growing trend in both annual publications and citations related to NAC in bladder cancer. The United States emerged as the predominant contributor in terms of publications, citations, and international collaborations. The University of Texas was the leading institution in publication output. “Urologic Oncology Seminars and Original Investigations” was the primary publishing journal, while “European Urology” boasted the highest impact factor. Shariat, Shahrokh F., and Grossman, H.B., were identified as the most prolific and co-cited authors, respectively. Keyword analysis revealed both frequency of occurrence and citation bursts, highlighting areas of concentrated study. Notably, the integration of immunochemotherapy is projected to experience substantial growth in forthcoming research.ConclusionsOur bibliometric assessment provides a panoramic view of the research milieu surrounding neoadjuvant chemotherapy for bladder cancer, encapsulating the present state, evolving trends, and potential future directions, with a particular emphasis on the promise of immunochemotherapy.

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with a poor prognosis. The underlying functions and mechanisms of circular RNA and SUMOylation in the development of ICC remain poorly understood. Methods Circular RNA hsa_circ_0001681 (termed Circ-RAPGEF5 hereafter) was identified by circular RNA sequencing from 19 pairs of ICC and adjacent tissue samples. The biological function of Circ-RAPGEF5 in tumor proliferation and metastasis was examined by a series of in vitro assays. A preclinical model was used to validate the therapeutic effect of targeting Circ-RAPGEF5. RNA pull-down and dual-luciferase reporter assays were used to access the RNA interactions. Western blot and Co-IP assays were used to detect SUMOylation levels. Results Circ-RAPGEF5, which is generated from exons 2 to 6 of the host gene RAPGEF5, was upregulated in ICC. In vitro and in vivo assays showed that Circ-RAPGEF5 promoted ICC tumor proliferation and metastasis, and inhibited apoptosis. Additionally, high Circ-RAPGEF5 expression was significantly correlated with a poor prognosis. Further investigation showed that SAE1, a potential target of Circ-RAPGEF5, was also associated with poor oncological outcomes. RNA pull-down and dual-luciferase reporter assays showed an interaction of miR-3185 with Circ-RAPGEF5 and SAE1. Co-IP and western blot assays showed that Circ-RAPGEF5 is capable of regulating SUMOylation. Conclusion Circ-RAPGEF5 promotes ICC tumor progression and SUMOylation by acting as a sponge for miR-3185 to stabilize SAE1. Targeting Circ-RAPGEF5 or SAE1 might be a novel diagnostic and therapeutic strategy in ICC.

Abstract Background Laparoscopic liver resection (LLR) is controversial in treating intrahepatic cholangiocarcinoma (ICC). Therefore, this study aimed to evaluate the safety and feasibility of LLR for the treatment of ICC and explored the independent factors affecting the long-term prognosis of ICC. Methods We included 170 patients undergoing hepatectomy for ICC from December 2010 to December 2021 and divided them into LLR group and open liver resection (OLR) group. We used propensity score matching (PSM) analysis to reduce the impact of data bias and confounding variables and then compared the short-term and long-term prognosis of LLR and OLR in treating ICC; Cox proportional hazards regression model was adopted to explore the independent factors affecting the long-term prognosis of ICC. Results A total of 105 patients (70 in the LLR group and 35 in the OLR group) were included after 2:1 PSM analysis. There was no difference in demographic characteristics and preoperative indexes between the two groups. The perioperative results of the OLR group were worse than those of the LLR group, that is, the intraoperative blood transfusion rate (24 (68.6) vs 21 (30.0)), blood loss (500 (200–1500) vs 200 (100–525)), and the morbidity of major postoperative complications (9 (25.7) vs 6 (8.5)) in the OLR group were worse than those in LLR group. LLR could enable patients to obtain an equivalent long-term prognosis compared to OLR. The Cox proportional hazards regression model exhibited that no matter before or after PSM, preoperative serum CA12-5 and postoperative hospital stay were independent factors affecting overall survival, while only lymph node metastasis independently influenced recurrence-free survival. Conclusions Compared with ICC treated by OLR, the LLR group obtained superior perioperative period outcomes. In the long run, LLR could enable ICC patients to receive an equivalent long-term prognosis compared to OLR. In addition, ICC patients with preoperative abnormal CA12-5, lymph node metastasis, and more extended postoperative hospital stay might suffer from a worse long-term prognosis. However, these conclusions still need multicenter extensive sample prospective research to demonstrate.

Background: Robotic liver resection is a hot topic in the field of liver surgery in recent years. We report our initial experience with robotic liver caudate lobectomy and discuss its safety. Methods: We retrospectively analyzed the clinical data of 13 patients who underwent the robotic liver caudate lobectomy between May 2018 and May 2021 in a single institution. The details of the surgical strategy were described. Results: All operations were performed robotically, and six operations were combined with other sites resection. The average operation time was 207.69 ​± ​104.81 ​min (single caudate lobectomy: 155.71 ​± ​45.41 ​min); intraoperative bleeding volume was 102.31 ​± ​158.84 ​ml (single: 42.14 ​± ​30.26 ​ml); and the average postoperative hospital stay was 5.08 ​± ​3.04 days (single: 3 ​± ​0.82 days). No deaths or serious surgical complications occurred perioperatively. Conclusion: This study suggests that robotic surgery is safe, effective, and feasible for liver caudate lobectomy.

Abstract Background With the development of digital pathology and the renewal of deep learning algorithm, artificial intelligence (AI) is widely applied in tumor pathology. Previous researches have demonstrated that AI-based tumor pathology may help to solve the challenges faced by traditional pathology. This technology has attracted the attention of scholars in many fields and a large amount of articles have been published. This study mainly summarizes the knowledge structure of AI-based tumor pathology through bibliometric analysis, and discusses the potential research trends and foci. Methods Publications related to AI-based tumor pathology from 1999 to 2021 were selected from Web of Science Core Collection. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. Results A total of 2753 papers were included. The papers on AI-based tumor pathology research had been continuously increased since 1999. The United States made the largest contribution in this field, in terms of publications (1138, 41.34%), H-index (85) and total citations (35,539 times). We identified the most productive institution and author were Harvard Medical School and Madabhushi Anant, while Jemal Ahmedin was the most co-cited author. Scientific Reports was the most prominent journal and after analysis, Lecture Notes in Computer Science was the journal with highest total link strength. According to the result of references and keywords analysis, “breast cancer histopathology” “convolutional neural network” and “histopathological image” were identified as the major future research foci. Conclusions AI-based tumor pathology is in the stage of vigorous development and has a bright prospect. International transboundary cooperation among countries and institutions should be strengthened in the future. It is foreseeable that more research foci will be lied in the interpretability of deep learning-based model and the development of multi-modal fusion model.

Background: Clostridioides (clostridium) difficile infection (CDI) is the most common cause of nosocomial diarrheal disease, which has become a public health problem worldwide; gut dysbiosis plays a central role in its pathophysiology. This study conducted a bibliometric analysis of publications on gut microbiota and CDI to summarize the current status of research including research hotspots. Methods: Relevant publications from January 2004 to February 2022 were identified from the Web of Science Core Collection. Three bibliometric tools were used to perform visualization analyses. Results: A total of 1983 publications were analyzed. Annual publications increased from 11 in 2004–237 in 2021, with the US being the leading producer (47.55 % of all papers). EG Pamer had the highest average citations per article (average citations per item = 153.03, H-index = 29). Frontiers in Microbiology published the most papers. The main research foci were “fecal microbiota transplantation,” “colonization resistance,” and “multidrug-resistant bacteria.” The keywords with the highest frequency in recent years include: gut dysbiosis, antibiotic resistance, bile-acids, 16 s sequencing, multidrug-resistant bacteria, and short chain fatty acids. Conclusions: Gut microbiota and CDI is likely to remain a prominent area of research in the foreseeable future. Current research hotspots (“fecal microbiota transplantation,” “colonization resistance,” and “multidrug-resistant bacteria”) should receive even more attention in future studies.

IntroductionInflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients’ quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses.MethodsGenome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis.ResultsGenetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn’s disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified.DiscussionThis study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.

Abstract Introduction Laparoscopic repeat hepatectomy (LRH) is considered to be a technically challenging procedure which has not been widely applied. This study aimed to assess the accessibility and security of LRH for patients with hepatic tumor recurrence. Methods Between January 2010 and October 2020, we performed 48 LRHs and 31 open repeat hepatectomies (ORHs) for recurrent liver cancer. LRHs were matched to ORHs (1:1) using propensity score matching (PSM) created by comparing preoperative factors. The perioperative data of patients were retrospectively analyzed, including baseline data, operative time, intraoperative blood loss, pathology, days of postoperative stay, complication morbidity, and mortality within 30 days. Overall survival and recurrence-free survival rates with appropriate follow-up were obtained to evaluate the long-term outcomes. Results Compared with the ORH, LRH was related with shorter operative duration (169.9 versus 232.9 ml, p < 0.01), less intraoperative bleeding (100.0 versus 500.0 ml, p < 0.01), lower rate of blood transfusion (8.3% versus 58.1%, p < 0.01), and shorter hospitalization (5.0 versus 11.0 days, p < 0.01). The median follow-up was 31 months. The LRH 1-, 3-, and 5-year overall survival were 77.1%, 61.6%, and 46.2% versus 82.3%, 66.5%, and 29.5% for ORH (p = 0.77). The 1-, 3-, and 5-year disease-free survival rates of the two groups were 73.4%, 62.0%, and 44.3% versus 66.1%, 44.1%, and 14.7%, respectively (p = 0.22). Conclusions Laparoscopic repeated hepatectomy is safe and practicable with great short-term results for selected patients.

Background: Ultrasound-triggered sonodynamic therapy (SDT), as a non-invasive approach, has attracted considerable attention in a wide variety of malignant tumors and other diseases. Over the past 2 decades, the number of scientific publications on SDT has increased rapidly. However, there is still a lack of one comprehensive report that summarizes the global research trends and knowledge landscapes in the field of SDT in detail. Thus, we performed a bibliometric analysis on SDT from 2000 to 2021 to track the current hotspots and highlight future directions.Methods: We collected publications on SDT research from the Web of Science Core Collection database. The annual number of publications and citations, major contributors, popular journals, international collaborations, co-cited references and co-occurrence keywords were analyzed and visualized with CiteSpace, VOSviewer, and R-bibliometrix.Results: A total of 701 publications were included. The annual publication output increased from 5 in 2000 to 175 in 2021, and the average growth rate was 18.4%. China was the most productive country with 463 documents (66.05%), and Harbin Medical University was the most prolific institution (N = 73). Ultrasound in Medicine and Biology published the most papers related to SDT. Materials Science, and Chemistry were the research areas receiving the most interest. All the keywords were divided into four different clusters including studies on mechanisms, studies on drug delivery and nanoparticles, studies on cancer therapy, as well as studies on ultrasound and sonosensitizers. In addition to nanomaterials-related studies including nanoparticles, mesoporous silica nanoparticles, nanosheets, liposomes, microbubble and TiO2 nanoparticle, the following research directions such as immunogenic cell death, metal-organic framework, photothermal therapy, hypoxia, tumor microenvironment, chemodynamic therapy, combination therapy, tumor resistance, intensity focused ultrasound, drug delivery, and Staphylococcus aureus also deserve further attention and may continue to explode in the future.Conclusion: SDT has a bright future in the field of cancer treatment, and nanomaterials have increasingly influenced the SDT field with the development of nano-technology. Overall, this comprehensive bibliometric study was the first attempt to analyze the field of SDT, which could provide valuable references for later researchers to better understand the global research trends, hotspots and frontiers in this domain.

Intravesical instillation of Bacillus Calmette-Guérin has been used as an immunotherapy to treat superficial bladder cancer for almost half a century. In recent years, the approval of several monoclonal antibody treatments has transformed the treatment landscape for patients with muscle-invasive or metastatic uroepithelial carcinoma. The purpose of this study was to conduct a thorough review of immunotherapy in bladder cancer through a bibliometric approach. Publications related to bladder cancer immunotherapy were obtained from the Web of Science Core Collection on July 1st, 2022. We conducted a bibliometric analysis of literature information using CiteSpace IV, VOSviewer, and Scimago Graphica, including co-authorship or co-citation of authors, countries/regions, journals, references, and keyword co-occurrence. There was a total of 2,352 papers included, with the most contributions coming from the United States, China, and Italy. The United States had the highest H-index value and was the leading country in this field. Meanwhile, the number of publications in China was steadily growing. The top three productive researchers were Kamat AM, Necchi A, and Shariat SF, with Powles T as the top co-cited author. Most papers were published by the University of Texas System. The majority of papers in this field were published in Urologic Oncology Seminars and Original Investigations and European Urology was the most influential journal with the highest H-index. The tumor microenvironment and complete molecular characterization may still be the frontier in this research area, allowing us to obtain a better understanding of the pathogenesis and clinical prognosis of bladder cancer. More research are conducted to identify clinically meaningful biomarkers that may provide opportunities for the personalization of bladder cancer therapy. This study provides clinicians and researchers with an overview and helpful guidance on how to choose the research direction and management of bladder cancer immunotherapy.

BackgroundProstate cancer (PCa) is the second most common malignancy in men worldwide. Growing evidence substantiates the important role of immunotherapy in human tumors. Given that immunotherapy is often unsatisfactory on PCa, many studies have been conducted on PCa immunotherapy to improve treatment efficacy. However, no relevant bibliometric study of PCa immunotherapy has hitherto been reported. A bibliometric analysis was performed to evaluate the global scientific production of PCa immunotherapy research and characterize the development trends for future studies in this article.MethodsThe publications related to PCa immunotherapy were extracted from the Web of Science Core Collection. The contribution and co-occurrence relationships of countries/regions, institutions, journals, references, authors, and keywords were assessed and visualized by VOSviewer and CiteSpace to identify research hotspots and potential future trends.ResultsA total of 3,583 publications related to PCa immunotherapy from 1999 to 2021 were collected. The results of annual publications and citations exhibited a steady increase over the past 22 years. The National Cancer Institute in the USA published far more papers during the study than any institute. Accordingly, the USA had the most publications (n = 1,954, 54.54%). Gulley, James L. had the most number of published papers, and Small, Eric J. was the most co-cited authors in this field. Cancer Immunology Immunotherapy was the most productive journal, with 145 publications on PCa immunotherapy. Keyword cluster and keyword burst analyses showed that research in PCa immunotherapy shifted from “t cell infiltration” and “sipuleucel t” to “immune checkpoint inhibitor”, “CTLA-4”, and “PD-L1 expression”.ConclusionPCa immunotherapy has attracted much attention, reflected by the increasing number of annual publications and citations. Much emphasis has been placed on exploring the complex immunogenicity and tumor microenvironment for PCa and identifying the patient population who can benefit from immunotherapy. Combining immune checkpoint inhibitors with other therapeutic options and cancer vaccines represents the future development trends in PCa immunotherapy.

BackgroundProstate cancer (PCa) is the second most diagnosed cancer in men. Most PCa-related deaths result from metastatic disease. Metastases occur most often in the bones (90%). However, the current treatments for bone metastases in PCa are not very effective. Here we present an overview of the current research situation of bone metastases in PCa, focusing on hotspots and trends.MethodsWe searched the Web of Science Core Collection database for publications related to bone metastases in PCa published between 1999 and 2021. We used VOSviewer, CiteSpace, and a bibliometric online platform to perform a bibliometric analysis of countries, institutions, authors, journals, references, and keywords.ResultsA total of 4,832 related articles were included in the present study. The USA published the most articles in the field, followed by China and England. The University of Texas MD Anderson Cancer Center is the leading institution in the research field of bone metastases in PCa. Saad F, from Canada, has made great achievements in this area by publishing 91 related articles. Prostate is the journal which published most related articles, and Mundy GR, 2002, Nat Rev Cancer, is the most cited article in this field. Furthermore, the analysis of author keywords can be divided into five clusters: (1) diagnosis of PCa, (2) mechanism of bone metastasis, (3) drug treatments of bone metastases, (4) radiotherapy of bone metastases, and (5) treatments and prognosis of PCa.ConclusionsmCRPC has been the hottest topic in PCa in recent years. CT is the most common diagnostic method for bone metastases. Enzalutamide and radium-223, as important treatments for bone metastases in PCa, bring about widespread attention. Furthermore, the researchers focus on the tumor microenvironment and biomarkers to explore the mechanism and the therapeutic targets of bone metastases in PCa.

PurposeImmune checkpoint blockade agents were shown to provide a survival advantage in urothelial carcinoma, while some patients got minimal benefit or side effects. Therefore, we aimed to investigate the prognostic value of m6A methylation regulators, and developed a nomogram for predicting the response to atezolizumab in urothelial carcinoma patients.MethodsA total of 298 advanced urothelial carcinoma patients with response data in the IMvigor210 cohort were included. Differential expressions of 23 m6A methylation regulators in different treatment outcomes were conducted. Subsequently, a gene signature was developed in the training set using the least absolute shrinkage and selection operator (LASSO) regression. Based on the multivariable logistic regression, a nomogram was constructed by incorporating the gene signature and independent clinicopathological predictors. The performance of the nomogram was assessed by its discrimination, calibration, and clinical utility with internal validation.ResultsSix m6A methylation regulators, including IGF2BP1, IGF2BP3, YTHDF2, HNRNPA2B1, FMR1, and FTO, were significantly differentially expressed between the responders and non-responders. These six regulators were also significantly correlated with the treatment outcomes. Based on the LASSO regression analysis, the gene signature consisting of two selected m6A methylation regulators (FMR1 and HNRNPA2B1) was constructed and showed favorable discrimination. The nomogram integrating the gene signature, TMB, and PD-L1 expression on immune cells, showed favorable calibration and discrimination in the training set (AUC 0.768), which was confirmed in the validation set (AUC 0.755). Decision curve analysis confirmed the potential clinical usefulness of the nomogram.ConclusionsThis study confirmed the prognostic value of FMR1 and HNRNPA2B1, and constructed a nomogram for individualized prediction of the response to atezolizumab in patients with urothelial carcinoma, which may aid in making treatment strategies.

BackgroundCentral nervous system tumor (CNST) is one of the most complicated and lethal forms of human tumors with very limited treatment options. In recent years, growing evidence indicates that oncolytic virotherapy (OVT) has emerged as a promising therapeutic strategy for CNSTs. And a considerable amount of literature on OVT-CNSTs has been published. However, there are still no studies summarizing the global research trends and hotspots of this field through a bibliometric approach. To fulfill this knowledge gap, bibliometric analysis was conducted based on all publications relating to OVT-CNSTs since 2000s.MethodsWe searched the Web of Science Core Collection for all relevant studies published between 2000 and 2022. Four different tools (online analysis platform, R-bibliometrix, CiteSpace and VOSviewer) were used to perform bibliometric analysis and network visualization, including annual publication output, active journals, contribution of countries, institutions, and authors, references, as well as keywords.ResultsA total of 473 articles and reviews were included. The annual number of publications on OVT-CNSTs showed a significant increasing trend. Molecular Therapy and Cancer Research were the most active and co-cited journals, respectively. In terms of contributions, there is no doubt that the United States occupied a leading position with the most publications (n=307, 64.9%) and the highest H-index (57). The institution and author that contributed the largest number of publications were Ohio State University and Chiocca EA, respectively. As can be seen from citation analysis, the current studies mainly focused on preclinical and phase I/II clinical results of various oncolytic virus for CNSTs treatment. Keywords co-occurrence and burst analysis revealed that the following research topics including immunotherapy, T-cells, tumor microenvironment, vaccine, blood-brain-barrier, checkpoint inhibitors, macrophage, stem cell, and recurrent glioblastoma have been research frontiers of this field and also have great potential to continue to be research hotspots in the future.ConclusionThere has been increasing attention on oncolytic viruses for use as CNSTs therapeutics. Oncolytic immunotherapy is a topic of great concern in this field. This bibliometric study provides a comprehensive analysis of the knowledge base, research hotspots, development perspective in the field of OVT-CNSTs, which could become an essential reference for scholars in this area.

In recent years, ferroptosis has become a research hotspot in programmed cell death. Since the concept of ferroptosis was proposed, a growing number of articles have been published on this topic. Nevertheless, to our knowledge, these ferroptosis-related publications that have received a great deal of attention have not been quantitatively evaluated. In this study, we analyzed the top 100 most influential articles over the past decade through a bibliometric method to characterize the research status and trends in this field. Web of Science Core Collection was searched to identify relevant studies. After being manually screened, the top 100 most cited studies with original data were identified and analyzed. Bibliometric software including VOSviewer and R-Bibliometrix were used to perform visualization analysis. The citation frequency for the top 100 selected articles ranged from 135 to 3603 (326.6 citations on average). These articles originated from 25 countries/regions, with more than half originating from the United States and China. The most frequently nominated author was Stockwell BR from the Columbia University, and of the top 100 articles, 19 listed his name. Three core journals were Nature, Cell and Proceedings of the National Academy of Sciences of the United States of America. In addition to term of ferroptosis, these terms or phrases including cell death, cancer cell, GPX4, pathway, inhibitor, mechanism, iron, lipid peroxidation, resistance, erastin, sorafenib, P53, reactive oxygen species, necroptosis, apoptosis, glutathione peroxidase, ACSL4, autophagy, and SLC7A11 appeared more frequently in the top 100 articles. Overall, although much progress has been made, the research on ferroptosis is still at an early stage. The current attention in this field mainly focuses on potential regulatory mechanism and pathways including key ferroptosis-related genes/molecules, oxidant and antioxidant system, ferroptosis-inducing agents or nanomedicine for cancer therapy, as well as the role of ferroptosis in non-neoplastic disorders. Meanwhile, combination therapeutic strategies targeting ferroptosis in radiotherapy or immunotherapy also deserve further attention.

BackgroundRenal cell carcinoma (RCC) is one of the most lethal urological malignancies, and because early-stage RCC is asymptomatic, many patients present metastatic diseases at first diagnosis. With the development of immunotherapy, the treatment of RCC has entered a new stage and has made a series of progress. This study mainly outlines the knowledge map and detects the potential research hotspots by using bibliometric analysis.MethodsPublications concerning RCC immunotherapy from 2002 to 2021 in the Web of Science Core Collection were collected. Visualization and statistical analysis were mainly performed by freeware tools VOSviewer, CiteSpace, R software, and Microsoft Office Excel 2019.ResultsA total of 3,432 papers were collected in this study, and the annual number of papers and citations showed a steady growth trend. The United States is the leading country with the most high-quality publications and is also the country with the most international cooperation. The University of Texas MD Anderson Cancer Center is the most productive organization. The Journal of Clinical Oncology is the highest co-cited journal, and Brian I. Rini is both the most prolific author and the author with the largest centrality. The current research hotspots may be focused on “immune checkpoint inhibitors (ICIs),” “PD-1,” and “mammalian target of rapamycin.”ConclusionImmunotherapy has a bright future in the field of RCC treatment, among which ICIs are one of the most important research hotspots. The main future research directions of ICI-based immunotherapy may focus on combination therapy, ICI monotherapy, and the development of new predictive biomarkers.

A growing body of research has illuminated that photodynamic therapy (PDT) serves as an important therapeutic strategy in oncology and has become a hot topic in recent years. Although numerous papers related to cancer PDT (CPDT) have been published, no bibliometric studies have been conducted to summarize the research landscape, and highlight the research trends and hotspots in this field. This study collected 5,804 records on CPDT published between 2000 and 2021 from Web of Science Core Collection. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace, and one online platform. The annual publication and citation results revealed significant increasing trends over the past 22 years. China and the United States, contributing 56.24% of the total publications, were the main driving force in this field. Chinese Academy of Sciences was the most prolific institution. Photodiagnosis and Photodynamic Therapy and Photochemistry and Photobiology were the most productive and most co-cited journals, respectively. All keywords were categorized into four clusters including studies on nanomaterial technology, clinical applications, mechanism, and photosensitizers. “nanotech-based PDT” and “enhanced PDT” were current research hotspots. In addition to several nano-related topics such as “nanosphere,” “nanoparticle,” “nanomaterial,” “nanoplatform,” “nanomedicine” and “gold nanoparticle,” the following topics including “photothermal therapy,” “metal organic framework,” “checkpoint blockade,” “tumor microenvironment,” “prodrug” also deserve further attention in the near future.

BackgroundWith the rapid development of technology, artificial intelligence (AI) has been widely used in the diagnosis and prognosis prediction of a variety of diseases, including prostate cancer. Facts have proved that AI has broad prospects in the accurate diagnosis and treatment of prostate cancer.ObjectiveThis study mainly summarizes the research on the application of artificial intelligence in the field of prostate cancer through bibliometric analysis and explores possible future research hotspots.MethodsThe articles and reviews regarding application of AI in prostate cancer between 1999 and 2020 were selected from Web of Science Core Collection on August 23, 2021. Microsoft Excel 2019 and GraphPad Prism 8 were applied to analyze the targeted variables. VOSviewer (version 1.6.16), Citespace (version 5.8.R2), and a widely used online bibliometric platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references, and keywords in this field.ResultsA total of 2,749 articles were selected in this study. AI-related research on prostate cancer increased exponentially in recent years, of which the USA was the most productive country with 1,342 publications, and had close cooperation with many countries. The most productive institution and researcher were the Henry Ford Health System and Tewari. However, the cooperation among most institutions or researchers was not close even if the high research outputs. The result of keyword analysis could divide all studies into three clusters: “Diagnosis and Prediction AI-related study”, “Non-surgery AI-related study”, and “Surgery AI-related study”. Meanwhile, the current research hotspots were “deep learning” and “multiparametric MRI”.ConclusionsArtificial intelligence has broad application prospects in prostate cancer, and a growing number of scholars are devoted to AI-related research on prostate cancer. Meanwhile, the cooperation among various countries and institutions needs to be strengthened in the future. It can be projected that noninvasive diagnosis and accurate minimally invasive treatment through deep learning technology will still be the research focus in the next few years.

BackgroundSome studies have revealed a close relationship between metabolism-related genes and the prognosis of bladder cancer. However, the relationship between metabolism-related long non-coding RNAs (lncRNA) regulating the expression of genetic material and bladder cancer is still blank. From this, we developed and validated a prognostic model based on metabolism-associated lncRNA to analyze the prognosis of bladder cancer.MethodsGene expression, lncRNA sequencing data, and related clinical information were extracted from The Cancer Genome Atlas (TCGA). And we downloaded metabolism-related gene sets from the human metabolism database. Differential expression analysis is used to screen differentially expressed metabolism-related genes and lncRNAs between tumors and paracancer tissues. We then obtained metabolism-related lncRNAs associated with prognosis by correlational analyses, univariate Cox analysis, and logistic least absolute shrinkage and selection operator (LASSO) regression. A risk scoring model is constructed based on the regression coefficient corresponding to lncRNA calculated by multivariate Cox analysis. According to the median risk score, patients were divided into a high-risk group and a low-risk group. Then, we developed and evaluated a nomogram including risk scores and Clinical baseline data to predict the prognosis. Furthermore, we performed gene-set enrichment analysis (GSEA) to explore the role of these metabolism-related lncRNAs in the prognosis of bladder cancer.ResultsBy analyzing the extracted data, our research screened out 12 metabolism-related lncRNAs. There are significant differences in survival between high and low-risk groups divided by the median risk scoring model, and the low-risk group has a more favorable prognosis than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk score was closely related to the prognosis of bladder cancer. Then we established a nomogram based on multivariate analysis. After evaluation, the modified model has good predictive efficiency and clinical application value. Furthermore, the GSEA showed that these lncRNAs affected bladder cancer prognosis through multiple links.ConclusionsA predictive model was established and validated based on 12 metabolism-related lncRNAs and clinical information, and we found these lncRNA affected bladder cancer prognosis through multiple links.

BackgroundA survival benefit was observed in metastatic bladder cancer patients who underwent primary tumor resection, but it was still confusing which patients are suitable for the surgery. For this purpose, we developed a model to screen stage M1 patients who would benefit from primary tumor resection.MethodsPatients with metastatic bladder cancer were screened from the Surveillance, Epidemiology, and End Results database (2004–2016) and then were divided into surgery (partial or complete cystectomy) group and non-surgery group. To balance the characteristics between them, a 1:1 propensity score matching analysis was applied. A hypothesis was proposed that the received primary tumor resection group has a more optimistic prognosis than the other group. The multivariable Cox model was used to explore the independent factors of survival time in two groups (beneficial and non-beneficial groups). Logistic regression was used to build a nomogram based on the significant predictive factors. Finally, a variety of methods are used to evaluate our model.ResultsA total of 7,965 patients with metastatic bladder cancer were included. And 3,314 patients met filtering standards, of which 545 (16.4%) received partial or complete cystectomy. Plots of the Kaplan–Meier and subgroup analyses confirmed our hypothesis. After propensity score matching analysis, a survival benefit was still observed that the surgery group has a longer median overall survival time (11.0 vs. 6.0 months, p < 0.001). Among the surgery cohort, 303 (65.8%) patients lived longer than 6 months (beneficial group). Differentiated characteristics included age, gender, TNM stage, histologic type, differentiation grade, and therapy, which were integrated as predictors to build a nomogram. The nomogram showed good discrimination in both training and validation cohorts (area under the receiver operating characteristic curve (AUC): 0.806 and 0.742, respectively), and the calibration curves demonstrated good consistency. Decision curve analysis showed that the nomogram was clinically useful. Compared with TNM staging, our model shows a better predictive value in identifying optimal patients for primary tumor resection.ConclusionsA practical predictive model was created and verified, which might be used to identify the optimal candidates for the partial or complete cystectomy group of the primary tumor among metastatic bladder cancer.

Abstract Background Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are two representative bariatric surgeries. This study aimed to compare the effects of the LSG and LRYGB based on high-quality analysis and massive amount of data. Methods For this study databases of PubMed, Web of Science, EBSCO, Medline, and Cochrane Library were searched for articles published until January 2019 comparing the outcomes of LSG and LRYGB. Results This study included 28 articles. Overall, 9038 patients (4597, LSG group; 4441, LRYGB group) were included. The remission rate of type 2 diabetes mellitus (T2DM) in the LRYGB group was superior to that in the LSG group at the 3-years follow-up. Five-year follow-up results showed that LRYGB had an advantage over LSG for the percentage of excess weight loss and remission of T2DM, hypertension, dyslipidemia, and abnormally low-density lipoprotein. Conclusions In terms of the long-term effects of bariatric surgery, the effect of LRYGB was better than of LSG.

Abstract Background Immune checkpoint inhibitors, which are a milestone in anti-cancer therapy, have been applied in the treatment of multiple malignancies. Real-world data have suggested that smoking status may be associated with the efficacy of anti-PD-1/PD-L1 therapy. Hereby, to evaluate “smoking benefit or not”, we included numerous high-quality randomized controlled clinical trials (RCTs) without any restriction on category. Methods A systematic search of online database was performed from July 2010 to July 2019. Eligible studies included phase II/III RCTs comparing PD-1/PD-L1 inhibitors with chemotherapy in the treatment of multiple carcinomas and contained subgroup analysis of smoking status. Then, related hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) were pooled. Results In the initial meta-analysis, compared with chemotherapy, the OS of non-smokers (HR, 0.81; 95% CI, 0.67–0.98) and smokers (HR, 0.77; 95% CI, 0.71–0.83) were significantly prolonged with PD-1/PD-L1 inhibitors. Outcomes from subgroup analysis showed that in anti-PD-1/PD-L1 monotherapy groups, non-smokers showed no significant improvement in OS (HR, 0.94; 95% CI, 0.83–1.06), while the OS of smokers was significantly prolonged (HR, 0.79; 95% CI, 0.74–0.85); in groups of PD-1/PD-L1 inhibitors combined with chemotherapy, the OS of non-smokers (HR, 0.45; 95% CI, 0.28–0.71) and smokers (HR, 0.72; 95% CI, 0.61–0.85) were significantly prolonged. Combined ipilimumab and chemotherapy showed no significance in both groups. Conclusion Smokers benefit from either anti-PD-1/PD-L1 monotherapy or the combined regimen compared with chemotherapy. Considering cost-effectiveness, monotherapy was recommended to smokers. For non-smokers, only the combined regimen was feasible in non-small cell lung cancer.

Abstract Background By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical modality for duodenal gastrointestinal stromal tumors (GISTs). Methods Two authors independently searched PubMed, Web of Science, Embase, and the Cochrane Library for published articles comparing the long-term prognostic and clinicopathological factors of duodenal GIST patients undergoing PD versus LR. Relevant information was extracted and analyzed. Results After screening, 10 items comprising 623 cases were eventually included. This meta-analysis explicitly indicated that PD treatment was associated with worse long-term prognosis (hazard ratio = 1.93; 95% confidence interval [CI], 1.39–2.69; p 5/50 high-power fields; OR = 2.24; 95% CI, 1.42–3.52; p

Abstract Background In theory, proximal gastrectomy with double-tract reconstruction (PG-DT) was superior to total gastrectomy (TG) in hematologic and nutritional outcomes. However, its clinical effects in proximal early gastric cancer (EGC) have been controversial. Methods The purpose of this study was to investigate the outcomes of laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DT) for proximal EGC. For this systematic review and meta-analysis, we searched for articles published before December of 2018 in the following databases: PubMed, Web of Science, EBSCO, Medline, and Cochrane Library. Results The results showed no significant difference in the anastomotic stenosis (OR = 0.91, 95%CI = 0.33–2.50, p = 0.85) and reflux esophagitis (OR = 1.87, 95%CI = 0.62–5.65, p = 0.27) between LPG-DT and laparoscopic total gastrectomy (LTG). The vitamin B12 supplementation rate in the LPG-DT group was lower than the LTG group (OR = 0.06, 95%Cl = 0.01–0.59, p = 0.02). Conclusions Due to comparable clinical effect, PG-DT is comparable to TG for patients with proximal EGC. In addition, LPG-DT not only appears superior to TG in terms of preventing vitamin B12 deficiency, but also does not increase the risk of anastomotic stricture and reflux esophagitis.

Abstract Objective To analyze the prognostic value of programmed death factor ligand 1 (PD-L1) in colorectal cancer. Methods Electronic databases, such as PubMed, Web of Science, Embase, and Cochrane library, were searched to identify studies evaluating the PD-L1 expression and overall survival (OS) in these patients. Afterwards, the relevant data were extracted to perform the meta-analysis. Results A total of 3481 patients were included in 10 studies. The combined hazard ratio (HR) was 1.22 (95%CI = 1.01–1.48, P = 0.04), indicating that high expression of PD-L1 was significantly correlated with poor prognosis of colorectal cancer. Apropos of clinicopathological features, the merged odds ratio (OR) exhibited that highly expressed PD-L1 was firmly related to lymphatic invasion (OR = 3.49, 95%CI = 1.54–7.90, P = 0.003) and advanced stage (OR = 1.77, 95%CI = 1.41–2.23, P

Background: The existing studies on primary bladder lymphoma (PBL) are retrospective analyses based on individual cases or small series studies, and the research on PBL is not unified and in-depth enough at present because of the scarcity of PBL and the lack of relevant literature. This study is designed to develop and validate nomograms for overall survival (OS) and cancer-specific survival (CSS) prediction in patients with PBL. Methods: According to the Surveillance, Epidemiology, and End Results (SEER) database, 405 patients diagnosed with PBL from 1975 to 2016 were collected and randomly assigned to training (n = 283) and validation (n = 122) cohort. After the multivariable Cox regression, the OS and CSS nomograms were developed. The discrimination, calibration and clinical usefulness of the nomograms were assessed and validated, respectively, by the training and validation cohort. Furthermore, all of the patients were reclassified into high- and low-risk groups and their survival were compared through Kaplan-Meier method and log-rank test. Results: Age, subtype, Ann Arbor stage, radiation and chemotherapy were identified as independent prognostic factors for OS and age, sex, and subtype for CSS, then corresponding nomograms predicting the 3- and 5-year survival were constructed. The presented nomograms demonstrated good discrimination and calibration, which the C-index in the training and validation cohort were 0.744 (95% confidence interval [CI], 0.705–0.783) and 0.675 (95% CI, 0.603–0.747) for OS nomogram and 0.692 (95% CI, 0.632–0.752) and 0.646 (95% CI, 0.549–0.743) for CSS nomogram, respectively. Furthermore, the nomograms can be used to effectively distinguish Patients with PBL at high risk of death. The clinical usefulness of the nomograms was visually displayed by decision curve analysis. Conclusion: We updated the baseline characteristics of patients with PBL and constructed OS and CSS nomograms to predict their 3- and 5-year survival. Using these nomograms, it would be convenient to individually predict the prognosis of patients with PBL and provide guidance for clinical treatment.

Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary, pancreatic, and gastrointestinal surgery can inadvertently cause iatrogenic BDI. The commonly utilized clinical treatment of BDI is biliary-enteric anastomosis. However, removal of the Oddi sphincter, which serves as a valve control over the unidirectional flow of bile to the intestine, can result in complications such as reflux cholangitis, restenosis of the bile duct, and cholangiocarcinoma. Tissue engineering and biomaterials offer alternative approaches for BDI treatment. Reconstruction of mechanically functional and biomimetic structures to replace bile ducts aims to promote the ingrowth of bile duct cells and realize tissue regeneration of bile ducts. Current research on artificial bile ducts has remained within preclinical animal model experiments. As more research shows artificial bile duct replacements achieving effective mechanical and functional prevention of biliary peritonitis caused by bile leakage or obstructive jaundice after bile duct reconstruction, clinical translation of tissue-engineered bile ducts has become a theoretical possibility. This literature review provides a comprehensive collection of published works in relation to three tissue engineering approaches for biomimetic bile duct construction: mechanical support from scaffold materials, cell seeding methods, and the incorporation of biologically active factors to identify the advancements and current limitations of materials and methods for the development of effective artificial bile ducts that promote tissue regeneration.