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Background: Bibliometric analysis has become popular in recent years, and increasingly more articles focusing on a particular disease are being published. The present study was performed to analyse the 100 most frequently cited papers in liver cancer (LC). Methods: We searched the Thomson Reuters Web of Science database on 14 July 2018 to identify all potential manuscripts for this study. The search terms were 'liver cancer' and its synonyms. Manuscripts were listed in descending order by the total citations (TCs), and the 100 most frequently cited papers were identified and analysed by topic, journal, author, year and institution. Results: We retrieved 235 687 papers from the Web of Science database. The TC of the 100 most frequently cited papers in LC ranged from 612 to 5358. The 100 papers were published in 31 journals and came from nine countries. The University of Barcelona published the highest number of papers and had the most TC. Ten authors published more than one paper. Treatment of LC was the most widely studied topic. A significant correlation was found between the journal's 2017 impact factor and the TC (P = 0.003). Conclusion: We assessed the landmark papers in the field of LC. These 100 most frequently cited papers reflect major advances and several hot topics in LC during the recent decades. Our study is of great value for young investigators, provides insights into the trends of LC and can guide directions for future academic research. [ABSTRACT FROM AUTHOR]

The article presents several abstracts on medical topics including prognostic significance and correlation between Igr5 and regulatory T cells in gastric cancer, upper gastrointestinal toxicity in chronic ketamine abusers, and microwave versus radiofrequency ablation for hepatocellular carcinoma.

In this work, a self‐powered electrowetting valve (SPEV) driven by an energy‐harvesting triboelectric nanogenerator (TENG) is reported. The TENG (5 × 5 cm2) can produce an open‐circuit voltage of 380 V by applying a mechanical stimulus, which is much higher than the actuation voltage of the SPEV (130 V). Once actuated, the electrowetting valve can be instantly switched on at a response time of 0.18 s, allowing liquid reagent to flow through the valve. The SPEV can be used for simultaneous addition of multiple reagents in an enzyme‐linked immunosorbent assay on a paper‐based microfluidic analytical device (µPAD). This assay involves a chromogenic reaction that achieves effective detection of alpha‐fetoprotein, a critical tumor marker for early diagnosis of liver cancer. The SPEV reported in this work can be potentially used in other complex multiprocedure µPADs, which will potentially enable portable, accessible, and cost‐effective assays for early diagnosis, food safety, pollution detection, etc. A self‐powered electrowetting valve (SPEV) enabled by a triboelectric nanogenerator is demonstrated in this work. The SPEV allows an instantaneous flow of liquid reagent once agitated by a mechanical stimulus. Integrated with a microfluidic paper‐based device, the SPEV achieves simultaneous addition of multiple reagents in an enzyme‐linked immunosorbent essay, making it possible for portable, acccesible, and cost‐effective essays. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B is a major public health concern as one third of the world's population is infected with hepatitis B virus (HBV). The risk of HBV infection remains primarily through percutaneous or mucosal contact with infected blood or body fluids. Aim: To update the society on hepatitis B immunization strategies and its associated factors. Materials and Methods: The review paper utilized different search engines such as Pubmed Central, Scopus, Web of Science, Google Scholar, and so on to conduct this review paper. Results: Improving immunity through general vaccination recommendations has reduced the number of chronic hepatitis B cases among children and adolescents, but an influx of infections from endemic countries has increased the number of chronically infected adults. This is due to immigration from endemic countries to Hepatitis less burden areas like developed countries. Introduction of infant immunization programs in some countries has reportedly reduced the prevalence of HBV infection and reduced the incidence of liver cancer in children and young adults. Conclusion: While hepatitis B vaccination coverage is low, a significant number of people are not adhering to full hepatitis B vaccination posing a potential hazard to health. [ABSTRACT FROM AUTHOR]

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two‐stage meta‐analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person‐years]), follow‐up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person‐years]), follow‐up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p <.0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p <.0001) (n = 595,193; events = 4110). A two‐stage meta‐analytic approach showed similar results. This paper adds important population‐based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta‐analysis across studies with large number of subjects makes the results robust. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effects of laparoscopic repeat liver resection (LRLR) and open repeat liver resection (ORLR) on surgical site wound infection and pain in recurrent hepatocellular carcinoma. PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data were systematically searched for studies comparing LRLR with ORLR for the treatment of recurrent hepatocellular carcinoma, with a search timeframe from their inception to December 2022. Two investigators independently screened the literature, extracted information, and evaluated the quality of the studies according to the inclusion and exclusion criteria. This study was performed using RevMan 5.4 software. A total of 20 publications with 4380 patients were included, with 1108 and 3289 patients in the LRLR and ORLR groups, respectively. The results showed that LRLR significantly reduced surgical site wound infection rate (1.71% vs. 5.16%, odds ratio [OR]:0.32, 95% confidence interval [CI]: 0.18‐0.56, P <.001), superficial wound infection rate (1.29% vs. 4.92%, OR: 0.29, 95% CI: 0.14‐0.58, P <.001), bile leakage (3.34% vs. 6.05%, OR: 0.59, 95% CI: 0.39‐0.90, P =.01), organ/space wound infection rate (0.4% vs. 5.11%, OR: 0.23, 95% CI: 0.07‐0.81, P =.02), and surgical site wound pain (mean difference: −2.00, 95% CI: −2.99 to −1.02, P <.001). Thus, the findings of this study showed that LRLR for recurrent hepatocellular carcinoma significantly reduced wound infection rates and improved postoperative wound pain. [ABSTRACT FROM AUTHOR]

Background: For hepatocellular carcinoma and metastatic hepatic carcinoma, imaging is one of the main diagnostic methods. In clinical practice, diagnosis mainly relied on experienced imaging physicians, which was inefficient and cannot met the demand for rapid and accurate diagnosis. Therefore, how to efficiently and accurately classify the two types of liver cancer based on imaging is an urgent problem to be solved at present. Purpose: The purpose of this study was to use the deep learning classification model to help radiologists classify the single metastatic hepatic carcinoma and hepatocellular carcinoma based on the enhanced features of enhanced CT (Computer Tomography) portal phase images of the liver site. Methods: In this retrospective study, 52 patients with metastatic hepatic carcinoma and 50 patients with hepatocellular carcinoma were among the patients who underwent preoperative enhanced CT examinations from 2017–2020. A total of 565 CT slices from these patients were used to train and validate the classification network (EI‐CNNet, training/validation: 452/113). First, the EI block was used to extract edge information from CT slices to enrich fine‐grained information and classify them. Then, ROC (Receiver Operating Characteristic) curve was used to evaluate the performance, accuracy, and recall of the EI‐CNNet. Finally, the classification results of EI‐CNNet were compared with popular classification models. Results: By utilizing 80% data for model training and 20% data for model validation, the average accuracy of this experiment was 98.2% ± 0.62 (mean ± standard deviation (SD)), the recall rate was 97.23% ± 2.77, the precision rate was 98.02% ± 2.07, the network parameters were 11.83 MB, and the validation time was 9.83 s/sample. The classification accuracy was improved by 20.98% compared to the base CNN network and the validation time was 10.38 s/sample. Compared with other classification networks, the InceptionV3 network showed improved classification results, but the number of parameters was increased and the validation time was 33 s/sample, and the classification accuracy was improved by 6.51% using this method. Conclusion: EI‐CNNet demonstrated promised diagnostic performance and has potential to reduce the workload of radiologists and may help distinguish whether the tumor is primary or metastatic in time; otherwise, it may be missed or misjudged. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra‐ or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular‐targeted therapies, targeted radionuclide therapies and epigenetic modification‐based therapies. These topics are trending headlines and their combination with cell‐based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced. [ABSTRACT FROM AUTHOR]

Various signaling mechanisms contribute significantly to the development of multiple cancers. Small molecules with the potential of influencing a wide variety of molecular targets may prove as broad‐spectrum anticancer agents. Flavonoids from plant sources are strongly emerging as promising antineoplastic molecules because of their ability to hamper different cancer‐driving signaling pathways. Further, these flavonoids offer an additional benefit due to their congenital antioxidant potential. This paper discusses the anticancer activity of luteolin against a number of cancers including leukemias, prostate cancer, pancreatic cancer, breast cancer, lung cancer, colorectal cancer, melanoma, liver, gastric, and brain cancer. Strong emphasis has been laid on key molecular mechanisms impacted by luteolin for exerting antineoplastic effect. Importantly, certain epigenetic targets like histone deacetylases (HDACs), DNA methylation regulator enzymes that are influenced by this befitting flavone for inducing cytotoxicity in certain preclinical cancer models, have also been made the part of this review. Additionally, the significantly improved therapeutic benefits of luteolin in combination with other therapeutics are comprehensively discussed. The current loopholes in luteolin research are also considered, which may open novel routes for further valuable studies on this promising flavone. [ABSTRACT FROM AUTHOR]

Low levels of oxygen (hypoxia) have been reported in solid tumours. This hypoxic microenvironment modulates the expression of genes linked to a more aggressive disease. However, it is unclear if the expression of drug‐metabolizing enzymes as cytochromes P450 (CYPs) is affected by hypoxia in cancer. We aimed to define which cytochromes are affected by hypoxia using a liver cancer model in vitro. For this purpose, we assessed whole‐genome expression microarrays of HepG2 liver cancer cell line from free repository databases, looking for gene expression hypoxia‐associated profiles and selected those cytochromes with significant differences. Then, we corroborated their mRNA expression and protein levels by RT‐qPCR and western blot, respectively, as well as immunofluorescence. Based on microarray analysis, we found that the expression of CYP2S1 and CYP24A1 were up‐regulated with at least twice fold change compared with normoxia. The levels of mRNA and protein of CYP2S1 and CYP24A1 were increased significantly in hypoxic conditions (P <.05), and this tendency was also observed by immunofluorescence assays. Our data show that the expression of cytochromes CYP2S1 and CYP24A1 are induced in hypoxia, being the first time that CYP24A1 expression is associated with tumour hypoxia; which might have consequences in cancer progression and drug resistance. Significance of the study: Hypoxia is among the most important factors for cellular adaptation to stress. Especially in cancer, a major public health issue, hypoxia plays a substantial role in angiogenesis, metastasis and resistance to therapy. Tumoral hypoxia has been described at least in the brain, breast, cervical, liver, renal, lung, pancreatic and renal cancer. However, the understanding of how hypoxia drives cancer progression is still a major challenge. One emerging question is the role of hypoxia over the expression of drug‐metabolizing enzymes, with a significant impact on drug treatment. In this context, our paper focus on the effect of hypoxia on CYPs, which is an essential group of drug‐metabolizing enzymes. We show that hypoxia induces the expression of two members of the CYPs family: CYP2S1 and CYP24A1. Importantly, CYP2S1 is a major metabolizer of carcinogenic substances being relevant that hypoxia could promote this function. Interestingly, CYP24A1 limits the action of the active form of vitamin D, which is an anti‐proliferative factor in cancer. Our evidence shows for the first time that hypoxia can induce CYP24A1 expression, with a potential effect on cancer progression. Our contribution clarifies a particular effect of tumoral hypoxia and the implications will be useful in the understanding of the progression of cancer, the resistance to treatment and the development of alternative therapies. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Lin et al papers. To view these articles visit https://doi.org/10.1111/apt.13774 and https://doi.org/10.1111/apt.13849. [ABSTRACT FROM AUTHOR]

COVID-19 and liver cancer clinical trials: Not everything is lost Keywords: BTC; clinical trials; COVID-19; HCC; liver cancer; SARS-CoV-2 EN BTC clinical trials COVID-19 HCC liver cancer SARS-CoV-2 1541 1544 4 06/25/20 20200701 NES 200701 Since the first cases in Wuhan, China, during the month of December 2019, coronavirus disease (COVID-19) evolved into a worldwide emergency, becoming one of the deadliest pandemics of modern history. Furthermore, these patients do not always have a valid therapeutic standard-of-care alternative, so for us it was of utmost importance to ensure the continuum of care for these patients even during the pandemic. Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper. [Extracted from the article]

Aims: Primary mixed liver cancers (PLCs), combined hepatocellular‐cholangiocellular (cHCC‐CC) and intermediate‐cell carcinomas are rare tumours characterised by different molecular mechanisms. Nestin is a marker of progenitor cells with a promising application in human tumours. The aims of the present paper are (i) to determine the expression of Nestin in mixed PLCs; and (ii) to correlate the PLC immunoprofile with the gene expression in each tumour component. Methods and results: We selected 28 mixed PLCs, 13 (46.4%) cHCC‐CC and 15 (53.6%) intermediate‐cell carcinomas. The immunohistochemistry panel consisted of keratin 7, keratin 19, CD56 and Nestin. Next‐generation sequencing analysis was performed on 17 cases (27 specimens) using a multi‐gene custom panel. The differentiated HCC and CC components of cHCC‐CC were negative for Nestin in all cases. The intermediate areas of cHCC‐CC were immunoreactive for Nestin in 92.3% of cases, for CD56 in 76.9% and for K7/K19 in all cases. The immunoprofile of the intermediate‐cell carcinomas showed 73.3% of cases positive for Nestin and 66.7% for CD56. TP53 and TERT were the most frequently mutated genes (31.3% and 17.6% of samples, respectively). Mutations were also found in IDH1, IDH2, PIK3CA and NRAS genes. Intermediate and HCC areas of cHCC‐CC seemed to share the same mutational profile, and both harboured different mutations than the CC component. Conclusions: According to our preliminary data, Nestin was not expressed by hepatocellular or cholangiocellular‐cell components, but was expressed by most of the intermediate cells in PLCs, and therefore could be considered in the differential diagnosis of PLCs, together with mutational profile. [ABSTRACT FROM AUTHOR]

Accumulating experimental evidence has demonstrated that microRNAs (miRNAs) have a huge impact on numerous critical biological processes and they are associated with different complex human diseases. Nevertheless, the task to predict potential miRNAs related to diseases remains difficult. In this paper, we developed a Kernel Fusion‐based Regularized Least Squares for MiRNA‐Disease Association prediction model (KFRLSMDA), which applied kernel fusion technique to fuse similarity matrices and then utilized regularized least squares to predict potential miRNA‐disease associations. To prove the effectiveness of KFRLSMDA, we adopted leave‐one‐out cross‐validation (LOOCV) and 5‐fold cross‐validation and then compared KFRLSMDA with 10 previous computational models (MaxFlow, MiRAI, MIDP, RKNNMDA, MCMDA, HGIMDA, RLSMDA, HDMP, WBSMDA and RWRMDA). Outperforming other models, KFRLSMDA achieved AUCs of 0.9246 in global LOOCV, 0.8243 in local LOOCV and average AUC of 0.9175 ± 0.0008 in 5‐fold cross‐validation. In addition, respectively, 96%, 100% and 90% of the top 50 potential miRNAs for breast neoplasms, colon neoplasms and oesophageal neoplasms were confirmed by experimental discoveries. We also predicted potential miRNAs related to hepatocellular cancer by removing all known related miRNAs of this cancer and 98% of the top 50 potential miRNAs were verified. Furthermore, we predicted potential miRNAs related to lymphoma using the data set in the old version of the HMDD database and 80% of the top 50 potential miRNAs were confirmed. Therefore, it can be concluded that KFRLSMDA has reliable prediction performance. [ABSTRACT FROM AUTHOR]

To date, despite many scientific evidences, the guidelines of the principal hepatological societies, such as the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver, do not recognize the diagnostic superiority of magnetic resonance imaging (MRI) over computed tomography in the diagnosis of hepatocellular carcinoma (HCC) and, for the most part, do not contemplate the use of hepatospecific contrast media, such as gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB). The aim of this paper was to analyze the recent results of EOB-MRI in the study of chronic liver disease and the differences between the American Association for the Study of Liver Diseases and the Japan Society of Hepatology guidelines, of which the latter represents the most consolidated experience on EOB-MRI use for HCC diagnosis. Finally, a new diagnostic algorithm for HCC in patients under surveillance for chronic liver disease was formulated, which contemplates the use of EOB. This new diagnostic algorithm is based on the Japan Society of Hepatology algorithm but goes beyond it by adapting it to the Western world, taking into account both the difference between the two and the latest results concerning the diagnosis of HCC. This new diagnostic algorithm for HCC is proposed in order to provide useful diagnostic tools to all those Western countries where the use of EOB (more expensive than extracellular contrast media) is widespread but in which common strategies to manage the nodules that this new contrast agent allows identifying have not been available to date. [ABSTRACT FROM AUTHOR]

Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof‐of‐concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p and interacts with Ago2. Trp/Ago2/miR‐193a increases miR‐193a‐3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR‐103 and miR‐107 in the Trp complex enhance miR‐193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR‐193a complex interacts with Trp‐binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR‐193a‐3p complex is more efficient than miR‐193a‐3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA‐induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy. [ABSTRACT FROM AUTHOR]

Glucagon‐like peptide‐1 (GLP‐1) regulates glycemic excursions by augmenting insulin production and inhibiting glucagon secretion. Liraglutide, a long‐acting GLP‐1 analog, can improve glycemic control for treating type 2 diabetes and prevent neutrophil extravasation in inflammation. Here, we explored the role of liraglutide in the development and therapy of murine lung and liver cancers. In this study, liraglutide substantially decreased circulating neutrophil extracellular trap (NET) markers myeloperoxidase, elastase, and dsDNA in Lewis lung cancer (LLC) and Hepa1‐6 tumor‐bearing mice. Furthermore, liraglutide downregulated NETs and reactive oxygen species (ROS) of neutrophils in the tumor microenvironment. Functionally, in vitro experiments showed that liraglutide reduced NET formation by inhibiting ROS. In addition, we showed that liraglutide enhanced the anti‐tumoral efficiency of programmed cell death‐1 (PD‐1) inhibition in LLC and Hepa1‐6 tumor‐bearing C57BL/6 mice. However, the removal of NETs significantly weakened the antitumor efficiency of liraglutide. We further demonstrated that the long‐term antitumor CD8+ T cell responses induced by the combination therapy rejected rechallenges by respective tumor cell lines. Taken together, our findings suggest that liraglutide may promote the anti‐tumoral efficiency of PD‐1 inhibition by reducing NETs in lung and liver cancers. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Grigg et al and Cholongitas papers. To view these articles, visit https://doi.org/10.1111/apt.15253 and https://doi.org/10.1111/apt.15310. [ABSTRACT FROM AUTHOR]

Background and aim: Several papers have shown that preoperative inflammation-based prognostic scores and/or immunonutritional status are associated with survival in patients with hepatocellular carcinoma (HCC). However, the validity of prognostic factors of these scores remains controversial. This study aimed to validate the power of prognostic scores based on the preoperative inflammatory and immunonutritional indices of patients who underwent hepatectomy for HCC with curative intent. Methods: Clinicopathological parameters and inflammation-based prognostic scores and immunonutritional status, including the Glasgow Prognostic Score, neutrophil to lymphocyte ratio (NLR), and prognostic nutritional index (PNI), were retrospectively analyzed to identify the predictors of overall and recurrence-free survival in 256 patients. Results: In multivariate analysis, NLR was an independent prognostic factor for overall, and recurrence-free survival (hazard ratio [HR] 2.59, 95 % confidence interval [CI] 1.56-4.31, P < 0.001, and HR 2.11, 95 % CI 1.44-3.11, P < 0.001, respectively). Additionally, PNI was an independent predictor of overall survival (HR 2.01, CI 1.21-3.36, P = 0.007). Conclusions: The present study shows that the NLR and PNI based on preoperative inflammatory and immunonutritional indices are predictors of overall survival in patients who undergo hepatectomy for HCC with curative intent. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Ramai et al and Ramai & Facciorusso papers. To view these articles, visit https://doi.org/10.1111/apt.16335 and https://doi.org/10.1111/apt.16360 [ABSTRACT FROM AUTHOR]

Keywords: Ablation; COVID-19; Hepatocellular carcinoma; Surgery; TACE; Tyrosine kinase inhibitor EN Ablation COVID-19 Hepatocellular carcinoma Surgery TACE Tyrosine kinase inhibitor 1823 1825 3 07/23/20 20200801 NES 200801 As COVID-19, the disease caused by SARS-CoV-2, continues to have a profound impact on global health, there have been a number of guidelines recently published addressing the management of patients with liver disease during the COVID-19 pandemic including the recently published EASL-ESCMID Position Paper, guidelines issued by the International Liver Cancer Association and the American Association for the Study of Liver Diseases (1-3). Currently, there is no evidence suggesting that tyrosine kinase inhibitors increase the risk COVID-19 and currently our centre has continued their use on an outpatient basis in those patients who fit EASL guidelines(7). There is sound evidence that patients and their carers benefit from advanced planning and given the contagious and deadly nature of COVID-19, we believe that this should be a key discussion point when counselling patients for any treatment. [Extracted from the article]

Summary: Hepatitis B virus infection is the cause of liver diseases such as cirrhosis and liver cancer. Understanding the host‐virus mechanisms that mediate virus pathogenesis can help design better preventive measures for disease control. Mathematical models have been used alongside experimental data to provide insight into the role of immune responses during the acute and chronic hepatitis B infections as well as virus dynamics following administration of combined drug therapy. In this paper, we review several modeling studies on virus‐host interactions during acute infection, the virus‐host characteristics responsible for transition to chronic disease, and the efficacy and optimal control measures of drug therapy. We conclude by presenting our opinion on the future directions of the field. [ABSTRACT FROM AUTHOR]

Abstract: Partial hepatectomy and liver transplantation are potentially curative treatments in selected patients with hepatocellular carcinoma (HCC). Unfortunately, a high postoperative tumor recurrence rate significantly decreases long‐term survival outcomes. Among multiple prognostic factors, the presence of microvascular invasion (MVI) has increasingly been recognized to reflect enhanced abilities of local invasion and distant metastasis of HCC. Unfortunately, MVI can only currently be identified through histopathological studies on resected surgical specimens. Accurate preoperative tests to predict the presence of MVI are urgently needed. This paper reviews the current studies on incidence, pathological diagnosis, and classification of MVI; possible mechanisms of MVI formation; and preoperative prediction of the presence of MVI. Furthermore, focusing on how the postoperative management can be improved on histopathologically confirmed patients with HCC with MVI, and the potential roles of using predictive tests to estimate the risk of presence of MVI, helps in preoperative therapeutic decision‐making in patients with HCC. [ABSTRACT FROM AUTHOR]

Purpose In liver microwave ablation (MWA) surgery, the ablation area covers the tumor to generate tissue necrosis and treat the cancer. As the liver deforms during the operation, deviation between the target area determined during preoperative planning and the resultant ablation area is inevitable. Therefore, an accurate assessment of tumor coverage is crucial for treatment. Through registration between the pre- and postoperative livers, the ablation area is warped on the preoperative liver for the computation of tumor coverage. However, large deformations between the pre- and postoperative livers are caused by multiple factors, and these diverse deformations make registration a challenging task. The purpose of this paper was to develop an automatic method that can accurately register post- to preoperative livers. Methods In the proposed method, nonrigid deformations caused by respiratory movement and edema are separately considered and estimated by the local incompressible model in the registration of livers. The pre- and postoperative livers are first aligned by a rigid registration based on a convex hull. In the nonrigid registrations, local incompressible constraints are then set on the liver and the ablation area to estimate the deformations caused by respiratory movement and edema, respectively. The concatenation of the rigid and nonrigid deformations is used to warp the ablation area on the preoperative liver. Results The proposed method was evaluated using clinical CT datasets from 20 patients. The Dice similarity coefficient (DSC) between the preoperative and warped postoperative livers is 94.35%, the mean surface distance (MSD) between the livers is 1.65 mm, the mean Hausdorff distance (HDD) between the livers is 3.36 mm, and the mean corresponding distance (MCD) between the corresponding landmarks is 1.70 mm. Compared with five other state-of-the-art methods, the proposed method achieves automatic ablation assessment with highly accurate registration. Conclusions The proposed method achieves a high accuracy for registering the livers. The sizes and positions of the ablation area and tumor are accurately compared for the assessment of ablation surgery. [ABSTRACT FROM AUTHOR]

CD47 blockade has emerged as a promising immunotherapy against liver cancer. However, the optimization of its antitumor effectiveness using efficient drug delivery systems or combinations of therapeutic agents remains largely incomplete. Here, patients with liver cancer co‐expressing CD47 and CDC7 (cell division cycle 7, a negative senescence‐related gene) are found to have the worst prognosis. Moreover, CD47 is highly expressed, and senescence is inhibited after the development of chemoresistance, suggesting that combination therapy targeting CD47 and CDC7 to inhibit CD47 and induce senescence may be a promising strategy for liver cancer. The efficacy of intravenously administered CDC7 and CD47 inhibitors is limited by low uptake and short circulation times. Here, inhibitors are coloaded into a dual‐targeted nanosystem. The sequential release of the inhibitors from the nanosystem under acidic conditions first induces cellular senescence and then promotes immune responses. In an in situ liver cancer mouse model and a chemotherapy‐resistant mouse model, the nanosystem effectively inhibited tumor growth by 90.33% and 85.15%, respectively. Overall, the nanosystem in this work achieved the sequential release of CDC7 and CD47 inhibitors in situ to trigger senescence and induce immunotherapy, effectively combating liver cancer and overcoming chemoresistance. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood‐based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. Methods: A three‐phase multicentre study was conducted to screen, optimise and validate HCC‐specific differentially methylated regions (DMRs) using next‐generation sequencing and quantitative methylation‐specific PCR (qMSP). Results: Genome‐wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre‐ and postoperative plasma samples from 103 HCC patients and correlated with 2‐year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p <.001). Conclusions: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC‐specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at‐risk populations. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Ramai et al and Pirola & Sookoian papers. To view these articles, visit https://doi.org/10.1111/apt.16335 and https://doi.org/10.1111/apt.16357 [ABSTRACT FROM AUTHOR]

In this study, a series of trinitroaniline derivatives (TNA1‐8) were synthesized and investigated as potential antitumor agents for enzyme‐prodrug therapy. Enzymatic efficiency of Ssap‐NtrB on prodrug candidates was determined with HPLC analysis and kinetic studies. The anti‐proliferative properties of compounds were determined against four cancer cell lines (Hep3B, PC3, HT‐29, and Saos‐2) and a healthy cell line (HUVEC) via MTT assay. Intracellular and extracellular prodrug‐enzyme treatments were carried out on Hep3B cells. Herewith, the expression of the Ssap‐NtrB gene was confirmed with this study. IC50 values of piperidine and 1,3‐cyclohexyl derivatives (TNA4 and TNA7) were identified as 1.724 nM and 1.640 nM at extracellular conditions. In intracellular conditions, it was determined as 0.293 μM and 0.393 μM, respectively. In summary, 2,4,6‐trinitroaniline derivatives, especially compounds TNA4 and TNA7 might be used as prodrug candidates along with Ssap‐NtrB for hepatocellular carcinoma therapy and the development of new prodrugs at cancer treatments. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a form of malignancy with limited curative options available. To improve therapeutic outcomes, it is imperative to develop novel, potent therapeutic modalities. Ketoconazole (KET) has shown excellent therapeutic efficacy against HCC by eliciting apoptosis. However, its limited water solubility hampers its application in clinical treatment. Herein, a mitochondria‐targeted chemo‐photodynamic nanoplatform, CS@KET/P780 NPs, is designed using a nanoprecipitation strategy by integrating a newly synthesized mitochondria‐targeted photosensitizer (P780) and chemotherapeutic agent KET coated with chondroitin sulfate (CS) to amplify HCC therapy. In this nanoplatform, CS confers tumor‐targeted and subsequently pH‐responsive drug delivery behavior by binding to glycoprotein CD44, leading to the release of P780 and KET. Mechanistically, following laser irradiation, P780 targets and destroys mitochondrial integrity, thus inducing apoptosis through the enhancement of reactive oxygen species (ROS) buildup. Meanwhile, KET‐induced apoptosis synergistically enhances the anticancer effect of P780. In addition, tumor cells undergoing apoptosis can trigger immunogenic cell death (ICD) and a longer‐term antitumor response by releasing tumor‐associated antigens (TAAs) and damage‐associated molecular patterns (DAMPs), which together contribute to improved therapeutic outcomes in HCC. Taken together, CS@KET/P780 NPs improve the bioavailability of KET and exhibit excellent therapeutic efficacy against HCC by exerting chemophototherapy and antitumor immunity. [ABSTRACT FROM AUTHOR]

Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl‐CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle‐type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6‐HMGCS1‐YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non‐alcoholic fatty liver diseases‐ associated HCC. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain‐gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA‐ and DR‐related drugs for digestive system diseases. [ABSTRACT FROM AUTHOR]

Accurately identifies the cellular composition of complex tissues, which is critical for understanding disease pathogenesis, early diagnosis, and prevention. However, current methods for deconvoluting bulk RNA sequencing (RNA‐seq) typically rely on matched single‐cell RNA sequencing (scRNA‐seq) as a reference, which can be limiting due to differences in sequencing distribution and the potential for invalid information from single‐cell references. Hence, a novel computational method named SCROAM is introduced to address these challenges. SCROAM transforms scRNA‐seq and bulk RNA‐seq into a shared feature space, effectively eliminating distributional differences in the latent space. Subsequently, cell‐type‐specific expression matrices are generated from the scRNA‐seq data, facilitating the precise identification of cell types within bulk tissues. The performance of SCROAM is assessed through benchmarking against simulated and real datasets, demonstrating its accuracy and robustness. To further validate SCROAM's performance, single‐cell and bulk RNA‐seq experiments are conducted on mouse spinal cord tissue, with SCROAM applied to identify cell types in bulk tissue. Results indicate that SCROAM is a highly effective tool for identifying similar cell types. An integrated analysis of liver cancer and primary glioblastoma is then performed. Overall, this research offers a novel perspective for delivering precise insights into disease pathogenesis and potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

FGF19 hormone has pleiotropic metabolic functions, including the modulation of insulin sensitivity, glucose/lipid metabolism and energy homeostasis. On top of its physiological metabolic role, FGF19 has been identified as a potentially targetable oncogenic driver, notably in hepatocellular carcinoma (HCC). Nevertheless, FGF19 remained an attractive candidate for treatment of metabolic disease, prompting the development of analogs uncoupling its metabolic and tumor-promoting activities. Using pre-clinical mice models of somatic mutation driven HCC, we assessed the oncogenicity of FGF19 in combination with frequent HCC tumorigenic alterations: p53 inactivation, CTNNB1 mutation, CCND1 or MYC overexpression. Our data revealed a strong oncogenic cooperation between FGF19 and MYC. Most importantly, we show that this oncogenic synergy is conserved with a FGF19-analog Aldafermin (NGM282), designed to solely mimic the hormone's metabolic functions. In particular, even a short systemic treatment with recombinant proteins triggered rapid appearance of proliferative foci of MYC-expressing hepatocytes. The fact that FGF19 analog Aldafermin is not fully devoid of the hormone's oncogenic properties raises concerns in the context of its potential use for patients with damaged, mutation-prone liver. Synopsis: FGF19-analog Aldafermin, reportedly devoid of the hormone oncogenic properties, is envisioned as a therapeutic tool for the treatment of chronic liver diseases. Using pre-clinical mouse models, we found that FGF19 and Aldafermin cooperate with oncogenes implicated in liver carcinogenesis. FGF19/FGF15 cooperate with MYC, giving rise to aggressive, fast-growing tumors. Aldafermin retains oncogenic properties in the context of MYC overexpression. The hormone and its analog promote carcinogenesis through deregulation of identical pathways. FGF19-analog Aldafermin, reportedly devoid of the hormone oncogenic properties, is envisioned as a therapeutic tool for the treatment of chronic liver diseases. Using pre-clinical mouse models, we found that FGF19 and Aldafermin cooperate with oncogenes implicated in liver carcinogenesis. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Poynard et al and Drake and Bird papers. To view these articles, visit https://doi.org/10.1111/apt.15082 and https://doi.org/10.1111/apt.15119. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Wang et al papers. To view these articles, visit https://doi.org/10.1111/apt.15074 and https://doi.org/10.1111/apt.15142. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Menon et al papers. To view these articles visit https://doi.org/10.1111/apt.12185 and https://doi.org/10.1111/apt.15038. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Shao et al and Shao and Wu papers. To view these articles visit https://doi.org/10.1111/apt.14835 and https://doi.org/10.1111/apt.15014. [ABSTRACT FROM AUTHOR]

In this paper, variation tendency of phosphorylated Nrf2, as the activated form of native Nrf2, was studied in 107 primary hepatocellular carcinoma (HCC) specimens treated by curative hepatectomy. Moreover, the coexpression of oxidative stress markers Keap1 and pNrf2, and their association with pathological features were also evaluated based on those specimens. The results showed that preserved cytoplasmic Keap1 expression of cancer cells was observed in 59 HCCs, while reduced Keap1 expression was determined in remaining 48 ones. With regarding to nuclear pNrf2 expression, 75 HCCs were defined as high and the other 32 ones as low. There was a significant association between Keap1 and pNrf2 expression in HCCs. Higher pNrf2 expression was observed, at a more substantial proportion, in those specimens with reduced Keap1 expression, compared to those with preserved Keap1 expression. The subset with higher pNrf2 and reduced Keap1 expression was defined as pNrf2+ Keap1−. According to the analysis of prognosis, this subset was significantly associated with poor 5-year overall survival and worse disease-free survival in HCCs, indicating that pNrf2 and Keap1 were two-functional biomolecules, not only the oxidative stress markers but also biomarkers for prognosis of HCCs. [ABSTRACT FROM AUTHOR]

HSF1-mediated heat shock response is activated in most tumors and plays important roles in regulating tumor homeostasis. However, the signals underlying HSF1 activation is still not completely understood. In this paper, we find that glucose, the dominant tumor energy supplement, participates in regulating HSF1's activation in HCC cell lines. The immunoblotting results indicate that the phosphorylation of HSF1/S326, a hallmark of HSF1 activation, varies between the HCC cell lines (e.g., SMMC7721, HapG2, plc/prf5, and Chang-liver). Glucose, but not 2D-glucose, can induce the phosphorylation of HSF1 at S326 and upregulate the expression of HSF1's downstream alpha B-crystallin and Hsp70 as well as the none-heat shock proteins CSK2 and RBM23 in two tested hepatocellular carcinoma cell lines (prl/prf5 and SMMC7721). Rapamycin, an inhibitor of mTOR, can suppress the glucose-induced phosphorylation of HSF1/S326 and the expression of alpha B-crystallin. Knockdown of HSF1 with shRNA enhances the glucose-depletion-mediated inhibition of plc/prf5 cell proliferation. Our data reveal that HSF1 can be activated by glucose-mTOR pathway, providing an alternative pathway for targeting HSF1 in tumor therapy. [ABSTRACT FROM AUTHOR]

This article is linked to Liu et al paper. To view this article visit https://doi.org/10.1111/apt.13634. [ABSTRACT FROM AUTHOR]

Composite of polyaniline, bovine serum albumin and silver nanoparticles was used as the enriched immobilization matrix (EIM)‐cum‐electrode material for detection of liver cancer biomarker, α‐fetoprotein (AFP) in blood serum. In the sandwich biosensor, signal amplification was bestowed by EIM and detection probe. EIM entrapped large amount of capture antibody due to its higher surface area and amine‐rich nature, whereas detection probe enhanced the electrochemical signal during its binding with AFP. Biosensor exhibited excellent sensitivity, selectivity, reproducibility with a detection limit of 4.7 pg/mL. The amplification strategy adopted herein has potential for clinical detection of cancer biomarkers in point‐of‐care diagnostics. [ABSTRACT FROM AUTHOR]

Electrochemiluminescence (ECL) of poly‐amidoamine (PAMAM) dendrimers functionalized to Fe3O4 nanoparticles (PAMAM@Fe3O4 NPs) based on Ru(bpy)32+ complex is reported. Different generations of PAMAM dendrimer consisted of 5 (D5), 10 (D10), 8 (D8) and 16 (D16) surface primary amine‐terminated groups. D5@Fe3O4 NPs enhanced ECL emission in comparison to others. A possible mechanism is elucidated based on structural functionality of PAMAM with respect to amines, carbonyl, hydroxyl groups and size‐based diffusion. ECL biosensing of alpha‐fetoprotein (AFP) and glypican‐3 (GPC‐3) using 1 mM tri‐propylamine is demonstrated using D5@Fe3O4NP@antibodies as detection probes. Detection limit for AFP and GPC‐3 was 6 pg/mL and 0.03 pg/mL, respectively. [ABSTRACT FROM AUTHOR]

Purpose: In image-guided radio frequency ablation for liver cancer treatment, pre- and post-interventional CT images are typically used to verify the treatment success of the therapy. In current clinical practice, the tumor zone in the diagnostic, preinterventional images is mentally or manually mapped to the ablation zone in the post-interventional images to decide success of the treatment. However, liver deformation and differences in image quality as well as in texture of the ablation zone and the tumor area make the mental or manual registration a challenging task. Purpose of this paper is to develop an automatic framework to register the pre-interventional image to the post-interventional image. Methods: The authors propose a registration approach enabling a nonrigid deformation of the tumor to the ablation zone, while keeping locally rigid deformation of the tumor area. The method was evaluated on CT images of 38 patient datasets from Erasmus MC. The evaluation is based on Dice coefficients of the liver segmentation on both the pre-interventional and post-interventional images, and mean distances between the liver segmentations. Additionally, residual distances after registration between corresponding landmarks and local mean surface distance in the images were computed. Results: The results show that rigid registration gives a Dice coefficient of 87.9%, a mean distance of the liver surfaces of 5.53 mm, and a landmark error of 5.38 mm, while non-rigid registration with local rigid deformation has a Dice coefficient of 92.2%, a mean distance between the liver segmentation boundaries near the tumor area of 3.83 mm, and a landmark error of 2.91 mm, where a part of this error can be attributed to the slice spacing in the authors' CT images. Conclusions: This method is thus a promising tool to assess the success of RFA liver cancer treatment. [ABSTRACT FROM AUTHOR]

Background and Aim Anatomic left hepatic trisectionectomy ( ALHT) is a complex hepatic resection, and its outcomes in hepatocellular carcinoma ( HCC) still remain unclear. This paper focuses on the assessment of the safety and long-term effects of ALHT on intermediate and advanced HCC patients with tumors that occupy the left liver lobe. Methods This study performed a retrospective analysis of consecutive HCC patients who underwent ALHT in a single-center cohort between December 2004 and December 2011. Results ALHT was performed on 34 intermediate and advanced HCC patients (0.05%) of 17 064 HCC patients who had undergone hepatic resection. Among them, 12 (33.3%) developed postoperative complications. Based on the multivariate analysis, we found that a serum prealbumin level of 170 mg/L is associated with an increased risk of morbidity ( P = 0.008). The one-year, two-year, three-year, and five-year overall survival rates were 61%, 27%, 11%, and 11%, respectively. The median overall survival was 13 months (range, 2-89 months). Based on the multivariate analysis, we also found that patients with an A/G ratio < 1.5 are more likely to have poor prognosis than those with an A/G ratio ≥ 1.5 ( P = 0.014). Multiple tumors are associated with worse outcomes ( P = 0.020). Conclusions ALHT is safe for intermediate and advanced HCC patients with tumors that occupy the left lobe and with preoperative Child-Pugh class A liver function. Low preoperative serum prealbumin level may increase the risk of postoperative complications. Although early intrahepatic recurrence rate is high, some patients, especially those with a single tumor and normal A/G ratio, exhibit long-term survival. [ABSTRACT FROM AUTHOR]

Background: Only a few papers have focused on the surgical outcomes of patients with hepatocellular carcinoma (HCC) associated with the metabolic syndrome. We compared the outcomes of patients with metabolic HCC with those of patients with non-B, non-C HCC associated with other etiologies. Methods: Metabolic HCC was defined as HCC arising in patients with at least three of the following metabolic disorders: central obesity, dyslipidemia, hypertension, and diabetes mellitus. A total of 246 patients with non-B, non-C HCC were divided into three groups: metabolic HCC ( n = 35), alcoholic HCC ( n = 114), and cryptogenic HCC ( n = 97). Clinical characteristics, surgical data, and survival were compared among the three groups. Results: Metabolic HCC was diagnosed at a significantly higher age than alcoholic (75 vs. 68 years, P = 0.004) and cryptogenic HCCs (75 vs. 71 years, P = 0.027). Postoperative complications occurred significantly higher in patients with metabolic HCC compared with those with cryptogenic HCC (40.0 vs. 22.7 %, P = 0.049). Especially, pulmonary complications were significant in metabolic HCC compared with cryptogenic HCC (22.9 vs. 8.2 %, P = 0.023). The overall survival rates in the metabolic, alcoholic, and cryptogenic HCC groups were 96.7 % (95 % CI, 90.5-100), 96.3 % (95 % CI, 92.8-99.9), and 95.6 % (95 % CI, 91.5-99.9) at 1 year, respectively, and 87.2 % (95 % CI, 74.5-100), 82.9 % (95 % CI, 74.6-92.2), and 84.5 % (95 % CI, 75.7-94.3) at 3 years, respectively ( P = 0.84). The disease-free survival rates in each group were 74.4 % (95 % CI, 60.5-91.5), 76.9 % (95 % CI, 69.2-85.5), and 74.3 % (95 % CI, 65.0-84.8) at 1 year, respectively, and 29.3 % (95 % CI, 16.6-51.8), 39.0 % (95 % CI, 29.7-51.2), and 41.1 % (95 % CI, 29.7-56.8) at 3 years, respectively, ( P = 0.90). Conclusions: Metabolic HCC patients have specific risks of postoperative complication related to the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood immunomarkers are associated with prognosis in patients with solid tumors receiving chemotherapy or immunotherapy. In this study, the associations of circulating neutrophil‐to‐lymphocyte ratio (NLR), monocyte‐to‐lymphocyte ratio (MLR), and platelet‐to‐lymphocyte ratio (PLR), as well as their dynamic changes were investigated in relation to the efficacy of immunotherapy in patients with primary liver cancer. Methods: Comparisons were made between NLR, MLR, and PLR among individuals exhibiting disease control (defined as the best response of partial response [PR] or stable disease [SD]) and those with progressive disease (PD). Additionally, disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) were compared between individuals with different NLR, MLR, and PLR levels before initiating palliative immunotherapy. Furthermore, comparisons were made between patients with different alterations in the ratios at the second cycle of immunotherapy compared to baseline. These analyses were performed using univariate and multivariate approaches. A total of 119 Chinese patients with liver cancer who underwent immunotherapy were included in this study, which focused on hepatocellular carcinoma (HCC). Results: In cases with HCC (n = 104), the cutoffs of NLR, MLR, and PLR to differentiate treatment responders from nonresponders were 3.38, 0.28, and 227.18, respectively. Patients with the best response of PR or SD had significantly lower NLR and MLR. Patients with NLR <3.38 and those with MLR <0.28 significantly had longer OS and PFS than their counterparts, and those with PLR <227.18 had significantly longer PFS, both in overall patients and in various patient subgroups. Lower NLR, MLR, or PLR was associated with earlier BCLC stage, fewer metastatic sites, less frequent extrahepatic metastasis, or better performance status. For individuals who had an unfavorable baseline NLR ≥3.38, MLR ≥0.28, or a favorable baseline PLR <227.18 prior to first immunotherapy, a decrease in NLR, MLR, or PLR at Cycle 2 of immunotherapy was significantly associated with a higher DCR. Conclusions: Among patients with HCC who received immunotherapy, lower NLR, and MLR at baseline in overall patients were significantly associated with better disease control and more favorable survival outcomes (both OS and PFS), and lower PLR was significantly associated with longer PFS. The findings of this research may offer useful hints foranoptimized selection of patients with liver cancer who may benefit more from immunotherapy. [ABSTRACT FROM AUTHOR]

A meta‐analysis research was implemented to appraise the effect of retrieval bags (RBs) in preventing surgical site wound infection (SSWI) in elective laparoscopic cholecystectomy (ELC) in liver cancer (LC) patients. Inclusive literature research until April 2023 was done, and 1273 interconnected researches were reviewed. From a total of 11 researches that were chosen, 2559 ELC procedures in LC patients were at the starting point of the researches: 1273 of them were utilising RBs and 1286 were controls. Odds ratio (OR) and 95% confidence intervals (CIs) were utilised to appraise the consequence of RBs in preventing SSWI in ELC in LC patients by the dichotomous approach and a fixed or random model. RBs had significantly lower SSWI (OR, 0.54; 95% CI, 0.38–0.76, p < 0.001) compared with controls in ELC in LC patients. However, no significant difference was found between RBs and controls in ELC in LC patients in bile spillage (OR, 0.51; 95% CI, 0.21–1.24, p = 0.14), fascial extension (OR, 0.54; 95% CI, 0.07–4.11, p = 0.55), postoperative collection (OR, 0.66; 95% CI, 0.24–1.76, p = 0.40) and port site hernia (OR, 0.72; 95% CI, 0.25–2.06, p = 0.54). RBs had significantly lower SSWI, and no significant difference was found in bile spillage, fascial extension, postoperative collection and port site hernia compared with controls in ELC in LC patients. However, caution needs to be taken when interacting with its values because there was a low sample size in some of the chosen researches and a low number of researches were found for some of the comparisons in the meta‐analysis. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Gounder et al papers. To view these articles visit https://doi.org/10.1111/apt.14026 and https://doi.org/10.1111/apt.13621. [ABSTRACT FROM AUTHOR]