Global, regional, and national burden of pancreatitis in older adults, 1990-2019: A systematic analysis for the global burden of disease study 2019.

Background: To describe the past, present and future burden of pancreatitis in older adults, and to explore cross-national inequalities across socio-demographic index (SDI). Methods: Data on pancreatitis in older adults, including mortality and disability-adjusted life years (DALYs) rates, were collected from the Global Burden of Disease (GBD) 2019 study. Temporal trends were measured using joinpoint analyses and predicted using a Bayesian age-period-cohort model. Additionally, the unequal distribution of the burden of pancreatitis in older adults was quantified. Results: From 1990 to 2019, the number of deaths and DALYs due to pancreatitis in older adults has been increasing annually. However, in most regions of the world, age-standardized death rates (ASDR) and age-standardized DALYs rates have been declining. The burden of pancreatitis in older adults was highest in low SDI region, primarily affecting the population aged 65-74, with a greater burden on males than females. Furthermore, from 1990 to 2019, absolute and relative cross-national inequalities in pancreatitis among older adults have remained largely unchanged. It is projected that in the next 11 years, the number of deaths in older adults due to pancreatitis will continue to increase, but the ASDR is expected to decline. Conclusion: Over the past 30 years, the ASDR and age-standardized DALYs rate of pancreatitis in older adults have shown a decline globally, but the absolute burden continues to increase. Cross-national health inequalities persist. Therefore, it is necessary to develop targeted intervention measures and enhance awareness among this vulnerable population regarding the risk factors associated with pancreatitis.

Interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma after hepatectomy: a multicenter population-based study.

An interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma (ES-HHCC) after hepatectomy is still lacking. This study was aimed at exploring the independent risk parameters and developing an interactive model for predicting the cancer-specific survival (CSS) of ES-HHCC. Data from patients with ES-HHCC who underwent hepatectomy were collected. The dimensionality of the clinical features was reduced by least absolute shrinkage and selection operator regression and further screened as predictors of CSS by Cox regression. Then, an interactive prediction model was developed and validated. Among the 514 screened patients, 311 and 203 of them were assigned into the training and validation cohort, respectively. Six independent variables, including alpha-fetoprotein, cirrhosis, microvascular invasion, satellite, tumor morphology, and tumor diameter, were identified and incorporated into the prediction model for CSS. The model achieved C-indices of 0.724 and 0.711 in the training and validation cohorts, respectively. Calibration curves showed general consistency in both cohorts. Compared with single predictor, the model had a better performance and greater benefit according to the time-independent receiver operating characteristic curve and decision curve analysis (P < 0.05). The calculator owned satisfactory accuracy and flexible operability for predicting the CSS of ES-HHCC, which could serve as a practical tool to stratify patients with different risks, and guide decision-making.

RNF125­mediated ubiquitination of MCM6 regulates the proliferation of human liver hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. Minichromosome maintenance proteins (MCMs), particularly MCM2-7, are upregulated in various cancers, including HCC. The aim of the present study was to investigate the role of MCM2-7 in human liver HCC (LIHC) and the regulation of the protein homeostasis of MCM6 by a specific E3 ligase. Bioinformatics analyses demonstrated that MCM2-7 were highly expressed in LIHC compared with corresponding normal tissues at the mRNA and protein levels, and patients with LIHC and high mRNA expression levels of MCM2, MCM3, MCM6 and MCM7 had poor overall survival rates. Cell Counting Kit-8 and colony formation assays revealed that the knockdown of MCM2, MCM3, MCM6 or MCM7 in Huh7 and Hep3B HCC cells inhibited cell proliferation and colony formation. In addition, pull-down, co-immunoprecipitation and ubiquitination assays demonstrated that RNF125 interacts with MCM6 and mediates its ubiquitination. Furthermore, co-transfection experiments indicated that RNF125 promoted the proliferation of HCC cells mainly through MCM6. In summary, the present study suggests that the RNF125-MCM6 axis plays an important role in the regulation of HCC cell proliferation and is a promising therapeutic target for the treatment of LIHC.

Prognoses of Patients Treated With Surgical Therapy Versus Continuation of Local-Plus-Systemic Therapy Following Successful Down-Staging of Intermediate-Advanced Hepatocellular Carcinoma: A Multicenter Real-World Study.

BACKGROUND: The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy. The differences between long-term prognoses of the 2 groups were compared. Subgroup analysis was performed in 173 HCC patients who met the criteria for surgical resection following down-staging. RESULTS: Multivariable analysis of all patients showed that surgical therapy, hazard ratio (HR): 0.289, 95% confidence interval, CI, 0.136-0.613) was a protective factor for overall survival (OS), but not for event-free survival (EFS). Multivariable analysis of 173 intermediate-advanced HCC patients who met the criteria for surgical resection after conversion therapy showed that surgical therapy (HR: 0.282, 95% CI, 0.121-0.655) was a protective factor for OS, but not for EFS. Similar results were obtained after propensity score matching. For patients with Barcelona Clinic Liver Cancer stage B (HR: 0.171, 95% CI, 0.039-0.751) and C (HR: 0.269, 95% CI, 0.085-0.854), surgical therapy was also a protective factor for OS. CONCLUSIONS: Overall, for patients with intermediate-advanced HCC who underwent local-plus-systemic therapies, surgical therapy is a protective factor for long-term prognosis and can prolong OS, and for those who met the surgical resection criteria after conversion therapy, surgical therapy is recommended.

LCRNet: local cross-channel recalibration network for liver cancer classification based on CT images.

Liver cancer is the leading cause of mortality in the world. Over the years, researchers have spent much effort in developing computer-aided techniques to improve clinicians' diagnosis efficiency and precision, aiming at helping patients with liver cancer to take treatment early. Recently, attention mechanisms can enhance the representational power of convolutional neural networks (CNNs), which have been widely used in medical image analysis. In this paper, we propose a novel architectural unit, local cross-channel recalibration (LCR) module, dynamically adjusting the relative importance of intermediate feature maps by considering the roles of different global context features and building the local dependencies between channels. LCR first extracts different global context features and integrates them by global context integration operator, then estimates per channel attention weight with a local cross-channel interaction manner. We combine the LCR module with the residual block to form a Residual-LCR module and construct a deep neural network termed local cross-channel recalibration network (LCRNet) based on a stack of Residual-LCR modules to recognize live cancer atomically based on CT images. Furthermore, This paper collects a clinical CT image dataset of liver cancer, AMU-CT, to verify the effectiveness of LCRNet, which will be publicly available. The experiments on the AMU-CT dataset and public SD-OCT dataset demonstrate our LCRNet significantly outperforms state-of-the-art attention-based CNNs. Specifically, our LCRNet improves accuracy by over 11% than ECANet on the AMU-CT dataset. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00263-6.

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study.

PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment.

The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors.

Online calculators for predicting the risk of anastomotic stricture after hepaticojejunostomy for bile duct injury after cholecystectomy: a multicenter retrospective study.

BACKGROUND: Anastomotic stricture is a common underlying cause of long-term morbidity after hepaticojejunostomy (HJ) for bile duct injury (BDI) following cholecystectomy. However, there are no methods for predicting stricture risk. This study was aimed at establishing two online calculators for predicting anastomotic stricture occurrence (ASO) and stricture-free survival (SFS) in this patient population. METHODS: The clinicopathological characteristics and follow-up information of patients who underwent HJ for BDI after cholecystectomy from a multi-institutional database were reviewed. Univariate and multivariate analyses of the risk factors of ASO and SFS were performed in the training cohort. Two nomogram-based online calculators were developed and validated by internal bootstrapping resamples ( n =1000) and an external cohort. RESULTS: Among 220 screened patients, 41 (18.64%) experienced anastomotic strictures after a median follow-up of 110.7 months. Using multivariate analysis, four variables, including previous repair, sepsis, HJ phase, and bile duct fistula, were identified as independent risk factors associated with both ASO and SFS. Two nomogram models and their corresponding online calculators were subsequently developed. In the training cohort, the novel calculators achieved concordance indices ( C -indices) of 0.841 and 0.763 in predicting ASO and SFS, respectively, much higher than those of the above variables. The predictive accuracy of the resulting models was also good in the internal ( C -indices: 0.867 and 0.821) and external ( C -indices: 0.852 and 0.823) validation cohorts. CONCLUSIONS: The two easy-to-use online calculators demonstrated optimal predictive performance for identifying patients at high risk for ASO and with dismal SFS. The estimation of individual risks will help guide decision-making and long-term personalized surveillance.

The value of three-dimensional visualization techniques in hepatectomy for complicated hepatolithiasis: A propensity score matching study.

OBJECTIVE: The present study aimed to investigate the safety, feasibility, and efficacy of three-dimensional visualization technique (3DVT)-guided hepatectomy in the treatment of complicated hepatolithiasis. METHODS: The clinical and follow-up data of 279 patients with complicated hepatolithiasis were retrospectively analyzed. The patients were divided into a 3DVT group (group A, 66 cases) and a non-3DVT group (group B, 213 cases). After baseline data were balanced using propensity score matching (PSM), the clinical characteristics and follow-up data of the two groups were observed. RESULTS: After 1:1 PSM, 58 patients in each group were successfully matched with each other. When the groups were compared, the surgical duration (p = 0.033) and intraoperative blood loss (p = 0.002) of group A were lower than those of group B. The immediate stone clearance rate (91.4% vs. 75.9%, p = 0.024) and quality of life outcome (p = 0.034) of group A were significantly higher than those of group B. Logistic regression analysis showed that history of two or more biliary tract operations (odds ratio [OR] = 6.544, 95% confidence interval [CI] = 1.193-35.890, p = 0.031), bilateral stone distribution (OR = 4.198, 95% CI = 1.186-14.854, p = 0.026), and Geng grade III or IV (OR = 12.262, 95% CI = 2.224-67.617, p = 0.004) were independent risk factors for poor outcomes in patients with complicated hepatolithiasis. CONCLUSION: Compared to conventional imaging examinations, 3DVT can be used to guide and achieve accurate preoperative diagnosis of complicated hepatolithiasis and has good safety, feasibility, and efficacy.

Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients.

BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.

Adjuvant immunotherapy improves recurrence-free and overall survival following surgical resection for intermediate/advanced hepatocellular carcinoma a multicenter propensity matching analysis.

Background & aims: The effectiveness of adjuvant immunotherapy to diminish recurrence and improve long-term prognosis following curative-intent surgical resection for hepatocellular carcinoma (HCC) is of increased interest, especially among individuals at high risk of recurrence. The objective of the current study was to investigate the impact of adjuvant immunotherapy on long-term recurrence and survival after curative resection among patients with intermediate/advanced HCC. Methods: Using a prospectively-collected multicenter database, patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC were identified. Propensity score matching (PSM) analysis was used to compare recurrence-free survival (RFS) and overall survival (OS) between patients treated with and without adjuvant immune checkpoint inhibitors (ICIs). Multivariate Cox-regression analysis further identified independent factors of RFS and OS. Results: Among the 627 enrolled patients, 109 patients (23.3%) received adjuvant immunotherapy. Most ICI-related adverse reactions were grading I-II. PSM analysis created 99 matched pairs of patients with comparable baseline characteristics between patients treated with and without adjuvant immunotherapy. In the PSM cohort, the median RFS (29.6 vs. 19.3 months, P=0.031) and OS (35.1 vs. 27.8 months, P=0.036) were better among patients who received adjuvant immunotherapy versus patients who did not. After adjustment for other confounding factors on multivariable analyzes, adjuvant immunotherapy remained independently associated with favorable RFS (HR: 0.630; 95% CI: 0.435-0.914; P=0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P=0.013). Subgroup analyzes identified potentially prognostic benefits of adjuvant immunotherapy among patients with intermediate-stage and advanced-stage HCC. Conclusion: This real-world observational study demonstrated that adjuvant immunotherapy was associated with improved RFS and OS following curative-intent resection of intermediate/advanced HCC. Future randomized controlled trials are warranted to establish definitive evidence for this specific population at high risks of recurrence.

EIF3H stabilizes CCND1 to promotes intrahepatic cholangiocarcinoma progression via Wnt/ß-catenin signaling.

Cholangiocarcinoma (CCA) is a group of tumors that arise along the human biliary duct tree, ranking second in primary hepatic malignancies. Intrahepatic CCA (iCCA) represents about 10%-20% of CCAs. There is an increasing body of evidence suggesting that iCCAs' incidence and mortality have been increasing globally over the past few decades. In this study, we found that the EIF3H expression level in iCCA tissues was significantly increased compared to the adjacent non-cancerous tissues by immunohistochemistry analysis (IHC). A similar tendency of EIF3H mRNA and protein level was confirmed in iCCA cell lines using RT-qPCR and Western blot. EIF3H has been identified as a critical molecule that plays a pro-neoplasmic role in iCCA both in vivo and in vitro, such as proliferation, migration, and anti-apoptosis. Mechanistically, we found that EIF3H knockdown can promote the degradation of CCND1 and the proteolysis of CCND1 is mediated by ubiquitin-proteasome system (UPS). Thus, we come to the conclusion that EIF3H promotes proliferation and migration of iCCAs, inhibiting apoptosis of iCCA cells at the same time by stabilizing the CCND1 protein structure. Our findings provide insights into the mechanism of tumorigenesis role of EIF3H in iCCAs and a potential therapeutic target for iCCA treatment.

Online calculator for predicting the risk of malignancy in patients with pancreatic cystic neoplasms: A multicenter, retrospective study.

BACKGROUND: Efficient and practical methods for predicting the risk of malignancy in patients with pancreatic cystic neoplasms (PCNs) are lacking. AIM: To establish a nomogram-based online calculator for predicting the risk of malignancy in patients with PCNs. METHODS: In this study, the clinicopathological data of target patients in three medical centers were analyzed. The independent sample t-test, Mann-Whitney U test or chi-squared test were used as appropriate for statistical analysis. After univariable and multivariable logistic regression analysis, five independent factors were screened and incorporated to develop a calculator for predicting the risk of malignancy. Finally, the concordance index (C-index), calibration, area under the curve, decision curve analysis and clinical impact curves were used to evaluate the performance of the calculator. RESULTS: Enhanced mural nodules [odds ratio (OR): 4.314; 95% confidence interval (CI): 1.618-11.503, P = 0.003], tumor diameter ≥ 40 mm (OR: 3.514; 95%CI: 1.138-10.849, P = 0.029), main pancreatic duct dilatation (OR: 3.267; 95%CI: 1.230-8.678, P = 0.018), preoperative neutrophil-to-lymphocyte ratio ≥ 2.288 (OR: 2.702; 95%CI: 1.008-7.244, P = 0.048], and preoperative serum CA19-9 concentration ≥ 34 U/mL (OR: 3.267; 95%CI: 1.274-13.007, P = 0.018) were independent risk factors for a high risk of malignancy in patients with PCNs. In the training cohort, the nomogram achieved a C-index of 0.824 for predicting the risk of malignancy. The predictive ability of the model was then validated in an external cohort (C-index: 0.893). Compared with the risk factors identified in the relevant guidelines, the current model showed better predictive performance and clinical utility. CONCLUSION: The calculator demonstrates optimal predictive performance for identifying the risk of malignancy, potentially yielding a personalized method for patient selection and decision-making in clinical practice.

Development and validation of safety and efficacy-associated risk calculator for hepatocellular carcinoma in the elderly after resection (SEARCHER): A multi-institutional observational study.

BACKGROUND: Increased life expectancy and improved perioperative management have resulted in increased utilization of hepatectomy for hepatocellular carcinoma (HCC) among elderly patients. However, individualized model for predicting the surgical safety and efficacy is lacking. The present study aimed to develop a safety and efficacy-associated risk calculator for HCC in the elderly after resection (SEARCHER). METHODS: From an international multicenter database, elderly patients who underwent curative-intent hepatectomy for HCC were stratified by patient age: 65-69 years, 70-74 years, 75-79 years, and ≥80 years. Short- and long-term outcomes among the 4 groups were compared. Univariate and multivariate analyses of risk factors of postoperative major morbidity, cancer-specific survival (CSS) and overall survival (OS) were performed in the training cohort. A nomogram-based online calculator was then constructed and validated in the validation cohort. RESULTS: With increasing age, the risk of postoperative major morbidity and worse OS increased (P = 0.001 and 0.020), but not postoperative mortality and CSS (P = 0.577 and 0.890) among patients across the 4 groups. Based on three nomograms to predict major morbidity, CSS and OS, the SEARCHER model was constructed and made available at https://elderlyhcc.shinyapps.io/SEARCHER. The model demonstrated excellent calibration and optimal performance in both the training and validation cohorts, and performed better than the several commonly-used conventional scoring and staging systems of HCC. CONCLUSIONS: With higher potential postoperative major morbidity and worse OS as patients age, the decision of whether to perform a hepatectomy for HCC needs to be comprehensively considered in the elderly. The proposed SEARCHER model demonstrated good performance to individually predict safety and efficacy of hepatectomy in elderly patients with HCC.

Prognostic Value of Drug Targets Predicted Using Deep Bioinformatic Analysis of m6A-Associated lncRNA-Based Pancreatic Cancer Model Characteristics and Its Tumour Microenvironment.

The role of N6-methyladenosine (m6A)-associated long-stranded non-coding RNA (lncRNA) in pancreatic cancer is unclear. Therefore, we analysed the characteristics and tumour microenvironment in pancreatic cancer and determined the value of m6A-related lncRNAs for prognosis and drug target prediction. An m6A-lncRNA co-expression network was constructed using The Cancer Genome Atlas database to screen m6A-related lncRNAs. Prognosis-related lncRNAs were screened using univariate Cox regression; patients were divided into high- and low-risk groups and randomised into training and test groups. In the training group, least absolute shrinkage and selection operator (LASSO) was used for regression analysis and to construct a prognostic model, which was validated in the test group. Tumor mutational burden (TMB), immune evasion, and immune function of risk genes were analysed using R; drug sensitivity and potential drugs were examined using the Genomics of Drug Sensitivity in Cancer database. We screened 129 m6A-related lncRNAs; 17 prognosis-related m6A-related lncRNAs were obtained using multivariate analysis and three m6A-related lncRNAs (AC092171.5, MEG9, and AC002091.1) were screened using LASSO regression. Survival rates were significantly higher (p < 0.05) in the low-risk than in the high-risk group. Risk score was an independent predictor affecting survival (p < 0.001), with the highest risk score being obtained by calculating the c-index. The TMB significantly differed between the high- and low-risk groups (p < 0.05). In the high- and low-risk groups, mutations were detected in 61 of 70 samples and 49 of 71 samples, respectively, with KRAS, TP53, and SMAD4 showing the highest mutation frequencies in both groups. A lower survival rate was observed in patients with a high versus low TMB. Immune function HLA, Cytolytic activity, and Inflammation-promoting, T cell co-inhibition, Check-point, and T cell co-stimulation significantly differed in different subgroups (p < 0.05). Immune evasion scores were significantly higher in the high-risk group than in the low-risk group. Eight sensitive drugs were screened: ABT.888, ATRA, AP.24534, AG.014699, ABT.263, axitinib, A.443654, and A.770041. We screened m6A-related lncRNAs using bioinformatics, constructed a prognosis-related model, explored TMB and immune function differences in pancreatic cancer, and identified potential therapeutic agents, providing a foundation for further studies of pancreatic cancer diagnosis and treatment.

Chinese expert consensus on conversion therapy for hepatocellular carcinoma (2021 edition).

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma (HCC) have resulted in improved response rates. This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection, a 'conversion therapy' strategy. However, conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed. Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice. Evidence review: Many research centers in China have accumulated significant experience implementing HCC conversion therapy. Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC; however, there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields. In order to summarize and learn from past experience and review current challenges, the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma (2021 Edition) was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice. Sixteen consensus statements on the implementation of conversion therapy for HCC were developed. The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

Development and Validation of a Prediction Model for Predicting the Prognosis of Postoperative Patients with Hepatocellular Carcinoma.

Purpose: The aims of this study were to identify the prognosis-related risk factors for HCC patients after surgery and to develop a predictive model by analysing the medical records of 152 HCC patients in our hospital. Patients and Methods: Univariate Cox regression analysis was applied to identify potential risk factors for HCC patients after surgery and to determine independent prognosis-related risk factors by multivariate analysis. Subsequently, a nomogram model was developed based on all independent factors and was validated by a validation set. Calibration and receiver operating characteristic curves were employed to evaluate the accuracy of the model. Finally, decision curve analyses were used to assess its clinical utility. Results: The univariate Cox regression analysis indicated that the patient's age, sex, grade, different AJCC TNM stages, vascular invasion, lymphatic infiltration, and tumour size were potential prognostic-related risk factors for HCC patients (p < 0.2), and the findings of multivariate analysis revealed that grade, different AJCC TNM stages, vascular invasion, and lymphatic infiltration were independent prognostic-related risk factors for HCC patients (p < 0.05). Subsequently, we constructed a prognosis-related prediction model based on all independent prognostic predictors and validated it with internal and external validation sets. The validation results indicated that the prediction model showed good accuracy (AUC = 0.81, 0.728) and consistency. More importantly, decision curve analysis illustrated that the nomogram model is a practical tool for predicting prognosis. Conclusion: This study found that grade, different AJCC TNM stages, vascular invasion, and lymphatic infiltration were independent prognosis-related predictors for HCC patients after surgery, and a nomogram model built on these predictors exhibited great accuracy and clinical usefulness.

Clinical online nomogram for predicting prognosis in recurrent hepatolithiasis after biliary surgery: A multicenter, retrospective study.

BACKGROUND: Methods for predicting the prognosis of patients undergoing surgery for recurrent hepatolithiasis after biliary surgery are currently lacking. AIM: To establish a nomogram to predict the prognosis of patients with recurrent hepatolithiasis after biliary surgery. METHODS: In this multicenter, retrospective study, data of consecutive patients in four large medical centers who underwent surgery for recurrent hepatolithiasis after biliary surgery were retrospectively analyzed. We constructed a nomogram to predict the prognosis of recurrent hepatolithiasis in a training cohort of 299 patients, following which we independently tested the nomogram in an external validation cohort of 142 patients. Finally, we used the concordance index (C-index), calibra-tion, area under curve, decision curve analysis, clinical impact curves, and visual fit indices to evaluate the accuracy of the nomogram. RESULTS: Multiple previous surgeries [2 surgeries: Odds ratio (95% confidence interval), 1.451 (0.719-2.932); 3 surgeries: 4.573 (2.015-10.378); ≥ 4 surgeries: 5.741 (1.347-24.470)], bilateral hepatolithiasis [1.965 (1.039-3.717)], absence of immediate clearance [2.398 (1.304-4.409)], neutrophil-to-lymphocyte ratio ≥ 2.462 [1.915 (1.099-3.337)], and albumin-to-globulin ratio ≤ 1.5 [1.949 (1.056-3.595)] were found to be independent factors influencing the prognosis. The nomogram constructed on the basis of these variables showed good reliability in the training (C-index: 0.748) and validation (C-index: 0.743) cohorts. Compared with predictions using traditional classification models, those using our nomogram showed better agreement with actual observations in the calibration curve for the probability of endpoints and the receiver operating characteristic curve. Dichloroacetate and clinical impact curves showed a larger net benefit of the nomogram. CONCLUSION: The nomogram developed in this study demonstrated superior performance and discriminative power compared to the three traditional classifications. It is easy to use, highly accurate, and shows excellent calibration.

Chinese Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021 Edition).

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the "Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)" based on current clinical studies and clinical medication experience for reference in China. Key Messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.