To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC...To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC)treated with liver transplantation(LT)[1].As a matter of fact,morphology and biology represent the two sides of the same展开更多
We read with great interest the article titled“Oncological survival in pancreatic head ductal carcinoma:hybrid minimally invasive versus open pancreatoduodenectomy-a single centre analysis”recently published in the ...We read with great interest the article titled“Oncological survival in pancreatic head ductal carcinoma:hybrid minimally invasive versus open pancreatoduodenectomy-a single centre analysis”recently published in the International Journal of Surgery(1).This research conducted a single centre and retrospective analysis to compare the oncological survival in patients with pancreatic head ductal carcinoma(PHDC)undergoing the hybrid minimally invasive versus open pancreatoduodenectomy.The study found that the laparoscopic procedure was significantly superior in terms of intraoperative blood loss(575 vs.600 mL,P=0.02)and operative time(413 vs.427 min,P=0.03),and that patients who underwent hybrid laparoscopic resection of PHDC showed significantly improved oncological outcomes.展开更多
BACKGROUND Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma(HCC),but its comparative efficacy remains under evaluation.AIM To evaluate the efficacy and safety of regorafenib vs ...BACKGROUND Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma(HCC),but its comparative efficacy remains under evaluation.AIM To evaluate the efficacy and safety of regorafenib vs other second-line therapies in advanced HCC.METHODS This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.A comprehensive search of PubMed,EMBASE,Web of Science,and the Cochrane Library was performed on June 6,2025.Studies were included if they reported at least one relevant clinical outcome:Overall survival,progression-free survival,objective response rate,or disease control rate.Data was extracted independently by two reviewers.Quality was assessed using the Cochrane Risk of Bias 2.0 tool for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies.Pooled effect estimates were calculated using random-or fixed-effects models depending on the degree of heterogeneity.Sensitivity analyses and Egger’s test were performed to evaluate the robustness of the results and potential publication bias.RESULTS Nine studies met inclusion criteria.Regorafenib significantly improved overall survival compared to controls[weighted mean difference=2.54 months;95%confidence interval(CI):0.26-4.81;P<0.05],but no significant benefit was observed for progression-free survival(weighted mean difference=1.04;95%CI:-1.27 to 3.36).The pooled objective response rate showed no overall difference,though regorafenib was inferior to nivolumab in subgroup analysis(odds ratio=0.34;95% CI:0.20-0.58).Disease control rate did not differ significantly.No publication bias was detected.CONCLUSION Regorafenib offers a survival advantage in advanced HCC but does not significantly improve tumor response rates compared to alternative therapies.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of pr...BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.展开更多
AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospecti...AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospective cohort study enrolled 29 patients diagnosed with OA-DLBCL based on histopathological biopsy between 2006 and 2023.Patients were stratified into two subgroups:primary OA-DLBCL(no prior history of lymphoma)and secondary OA-DLBCL(history of DLBCL at non-ocular adnexal sites).OS was defined as the time interval from OA-DLBCL diagnosis to death from any cause.Survival analysis was performed using the Kaplan–Meier method,and prognostic factors affecting OS were identified using multivariate Cox proportional hazards regression with a stepwise selection approach.RESULTS:The cohort included 24 patients with primary OA-DLBCL(13 males,11 females;mean age:61.36±18.29y)and 5 patients with secondary OA-DLBCL(2 males,3 females;mean age:50.94±18.17y).Among the primary OA-DLBCL subgroup,12 patients(50%)presented with advanced disease(Ann Arbor stage IIIE–IV),and 16 patients(66%)were classified as T4 disease according to the tumor-node-metastasis(TNM)staging system.The mean final visual acuity was 1.72±1.10 in the primary group and 0.90±1.18 in the secondary group.The 5-year OS rate for the entire cohort was 27.7%.Multivariate analysis identified five factors significantly associated with poor survival outcomes:epiphora[adjusted hazard ratio(aHR),36.95],atherosclerotic cardiovascular disease(aHR,10.08),human immunodeficiency virus(HIV)infection(aHR,12.47),M1 stage(aHR,6.99),and secondary OA-DLBCL(aHR,6.03;all P<0.05).The median OS was 1.68y for primary OA-DLBCL and 1.12y for secondary OA-DLBCL.CONCLUSION:A substantial proportion of patients with primary OA-DLBCL present with advanced-stage disease at diagnosis.Epiphora,atherosclerotic cardiovascular disease,HIV infection,M1 stage,and secondary OA-DLBCL are independent prognostic factors for poor survival outcomes.These findings emphasize the urgent need for optimized therapeutic strategies and early screening protocols to improve the management of OA-DLBCL,particularly in developing countries.展开更多
Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor...Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably ass...Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.展开更多
In this paper, we proposed a dynamic stress–strength model for coherent system. It is supposedthat the system consists of n components with initial random strength and each component issubjected to random stresses. T...In this paper, we proposed a dynamic stress–strength model for coherent system. It is supposedthat the system consists of n components with initial random strength and each component issubjected to random stresses. The stresses, applied repeatedly at random cycle times, will causethe degradation of strength. In addition, the number of cycles in an interval is assumed to followa Poisson distribution. In the case of the strength and stress random variables following exponential distributions, the expression for the reliability of the proposed dynamic stress–strengthmodel is derived based on survival signature. The reliability is estimated by using the best linearunbiased estimation (BLUE). Considering the Type-II censored failure times, the best linear unbiased predictors (BLUP) for the unobserved coherent system failure times are developed basedon the observed failure times. Monte Carlo simulations are performed to compare the BLUE ofparameters with different values and compute the BLUP. A real data set is also analysed for anillustration of the findings.展开更多
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteri...BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteristics and clinical results of oesophageal GISTs.AIM To investigate endoscopic treatment effective of oesophageal GISTs.METHODS It was retrospective research that collected 32 patients with oesophageal GISTs treated by endoscopic resection(ER)between January 2012 and January 2023 in two Hospital.Clinicopathologic,endoscopic records,and follow-up data were collected and analysed.RESULTS Thirty-one patients underwent en bloc resection and 24(75.0%)lesions underwent R0 resection.The size of GISTs was 2.12±1.88 cm.The overall complication rate was 25.0%,including hydrothorax and post-endoscopic submucosal dissection electrocoagulation syndrome.The mean mitotic index was 3.34±5.04(median,1.50;range,1.00-4.00).Eighteen(56.3%),6(18.8%),2(6.3%),and 6(18.8%)patients were identified as very low,low,intermediate,and high risk,respectively.Three patients developed recurrence after a median follow-up of 64.69±33.13 months.The 5-year overall survival rate was 100%,and the disease-free survival rate was 90.6%.CONCLUSION ER is safe and effective for patients with low-risk oesophageal GISTs.Early detection of oesophageal GISTs is essential to achieve a favourable prognosis.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases pos...BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.展开更多
Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarte...Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.展开更多
BACKGROUND Cholangiocarcinoma(CCA)comprises heterogeneous malignancies arising at different anatomical locations:Intrahepatic cholangiocarcinoma(IHCC),perihilar cholangiocarcinoma(PHCC),and distal cholangiocarcinoma(D...BACKGROUND Cholangiocarcinoma(CCA)comprises heterogeneous malignancies arising at different anatomical locations:Intrahepatic cholangiocarcinoma(IHCC),perihilar cholangiocarcinoma(PHCC),and distal cholangiocarcinoma(DCC).These subtypes exhibit distinct clinical behaviors,treatment approaches,and outcomes.Despite advances in surgical and adjuvant therapies,the prognostic implications of tumor location remain unclear and inconsistently reported.Understanding these variations is essential for personalized management and staging refinement.We hypothesized that the anatomical subtype of CCA significantly influences prognostic outcomes and pathological features.AIM To compare prognostic outcomes and clinicopathological characteristics among IHCC,PHCC,and DCC based on current evidence.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.PubMed,EMBASE,and the Cochrane Library were searched,yielding 11 eligible retrospective comparative studies involving 14484 patients(IHCC:6260;PHCC:6895;DCC:1329).Outcomes assessed included overall survival(OS),lymph node metastasis,neural invasion,and vascular invasion.Statistical analyses were performed using RevMan 5.3 and Stata 13.0.RESULTS DCC demonstrated the most favorable prognosis among all subtypes.Despite the highest lymph node metastasis rate(DCC:56.9%),it was associated with better OS than PHCC and IHCC.Vascular invasion was more prevalent in IHCC(OR=1.66,95%CI:1.22-2.28,P=0.001).OS comparisons showed no significant difference between PHCC and IHCC(HR=1.02,P=0.88),while DCC showed consistent trends toward better survival against both.CONCLUSION Anatomical subtype is a significant prognostic factor in CCA.DCC patients experience superior outcomes despite aggressive lymphatic spread,suggesting better resectability and surgical outcomes.These insights underscore the need for subtype-specific management strategies and future prospective validation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and life-threatening cancer with increasing incidence worldwide.High Ki-67 risk stratification is closely associated with higher recurrence rates and worse outcom...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and life-threatening cancer with increasing incidence worldwide.High Ki-67 risk stratification is closely associated with higher recurrence rates and worse outcomes following curative therapies in patients with HCC.However,the performance of radiomic and deep transfer learning(DTL)models derived from biparametric magnetic resonance imaging(bpMRI)in predicting Ki-67 risk stratification and recurrence-free survival(RFS)in patients with HCC remains limited.AIM To develop a nomogram model integrating bpMRI-based radiomic and DTL signatures for predicting Ki-67 risk stratification and RFS in patients with HCC.METHODS This study included 198 patients with histopathologically confirmed HCC who underwent preoperative bpMRI.Ki-67 risk stratification was categorized as high(>20%)or low(≤20%)according to immunohistochemical staining.Radiomic and DTL signatures were extracted from the T2-weighted and arterial-phase images and combined through a random forest algorithm to establish radiomic and DTL models,respectively.Multivariate regression analysis identified clinical risk factors for high Ki-67 risk stratification,and a predictive nomogram model was developed.RESULTS A nonsmooth margin and the absence of an enhanced capsule were independent factors for high Ki-67 risk stratification.The area under the curve(AUC)of the clinical model was 0.77,while those of the radiomic and DTL models were 0.81 and 0.87,respectively,for the prediction of high Ki-67 risk stratification,and the nomogram model achieved a better AUC of 0.92.The median RFS times for patients with high and low Ki-67 risk stratification were 33.00 months and 66.73 months,respectively(P<0.001).Additionally,patients who were predicted to have high Ki-67 risk stratification by the nomogram model had a lower median RFS than those who were predicted to have low Ki-67 risk stratification(33.53 vs 66.74 months,P=0.007).CONCLUSION Our developed nomogram model demonstrated good performance in predicting Ki-67 risk stratification and predicting survival outcomes in patients with HCC.展开更多
The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the ...The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.展开更多
BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical...BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.展开更多
Rectal neuroendocrine tumors(r-NETs)are the second most common type of neuroendocrine tumor in the gastrointestinal tract,with an increase in incidence in the last decades.They are low-grade tumors and,given their low...Rectal neuroendocrine tumors(r-NETs)are the second most common type of neuroendocrine tumor in the gastrointestinal tract,with an increase in incidence in the last decades.They are low-grade tumors and,given their low risk of meta-stasis,current guidelines recommend endoscopic resection for small lesions.The GATIS predicting score,proposed by Zeng et al,represents an innovative model designed to predict individualized survival outcomes for patients with r-NETs,analyzing the relationship between clinicopathological features and patient prog-noses.The authors identified tumor grade,T stage,tumor size,age,and progno-stic nutritional index as key prognostic factors,demonstrating that the GATIS Score provides a more accurate prognosis assessment compared to the World Health Organization classification or the tumor-node-metastasis staging system.Nevertheless,further larger prospective studies are necessary,and the scientific community's efforts in this context should be directed toward developing interna-tional multicentric prospective studies,with the ultimate aim of accurately de-fining and understanding the behavior of these conditions.展开更多
文摘To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC)treated with liver transplantation(LT)[1].As a matter of fact,morphology and biology represent the two sides of the same
基金supported by Guilin Science and Technology Plan Project(No.20220139-5-3)The Technology Project within the No.924 Hospital of PLA Joint Logistic Support Force(No.S2022FH01)+1 种基金Guangxi Healthcare Science and Technology Plan Project(No.Z-C20241574)The Fundamental Research Funds for the Central Universities of HIT.
文摘We read with great interest the article titled“Oncological survival in pancreatic head ductal carcinoma:hybrid minimally invasive versus open pancreatoduodenectomy-a single centre analysis”recently published in the International Journal of Surgery(1).This research conducted a single centre and retrospective analysis to compare the oncological survival in patients with pancreatic head ductal carcinoma(PHDC)undergoing the hybrid minimally invasive versus open pancreatoduodenectomy.The study found that the laparoscopic procedure was significantly superior in terms of intraoperative blood loss(575 vs.600 mL,P=0.02)and operative time(413 vs.427 min,P=0.03),and that patients who underwent hybrid laparoscopic resection of PHDC showed significantly improved oncological outcomes.
文摘BACKGROUND Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma(HCC),but its comparative efficacy remains under evaluation.AIM To evaluate the efficacy and safety of regorafenib vs other second-line therapies in advanced HCC.METHODS This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.A comprehensive search of PubMed,EMBASE,Web of Science,and the Cochrane Library was performed on June 6,2025.Studies were included if they reported at least one relevant clinical outcome:Overall survival,progression-free survival,objective response rate,or disease control rate.Data was extracted independently by two reviewers.Quality was assessed using the Cochrane Risk of Bias 2.0 tool for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies.Pooled effect estimates were calculated using random-or fixed-effects models depending on the degree of heterogeneity.Sensitivity analyses and Egger’s test were performed to evaluate the robustness of the results and potential publication bias.RESULTS Nine studies met inclusion criteria.Regorafenib significantly improved overall survival compared to controls[weighted mean difference=2.54 months;95%confidence interval(CI):0.26-4.81;P<0.05],but no significant benefit was observed for progression-free survival(weighted mean difference=1.04;95%CI:-1.27 to 3.36).The pooled objective response rate showed no overall difference,though regorafenib was inferior to nivolumab in subgroup analysis(odds ratio=0.34;95% CI:0.20-0.58).Disease control rate did not differ significantly.No publication bias was detected.CONCLUSION Regorafenib offers a survival advantage in advanced HCC but does not significantly improve tumor response rates compared to alternative therapies.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
文摘BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.
基金Supported by the Faculty of Medicine,Prince of Songkla University.Wainipitapong S has received grants from the Faculty of Medicine,Prince of Songkla University。
文摘AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospective cohort study enrolled 29 patients diagnosed with OA-DLBCL based on histopathological biopsy between 2006 and 2023.Patients were stratified into two subgroups:primary OA-DLBCL(no prior history of lymphoma)and secondary OA-DLBCL(history of DLBCL at non-ocular adnexal sites).OS was defined as the time interval from OA-DLBCL diagnosis to death from any cause.Survival analysis was performed using the Kaplan–Meier method,and prognostic factors affecting OS were identified using multivariate Cox proportional hazards regression with a stepwise selection approach.RESULTS:The cohort included 24 patients with primary OA-DLBCL(13 males,11 females;mean age:61.36±18.29y)and 5 patients with secondary OA-DLBCL(2 males,3 females;mean age:50.94±18.17y).Among the primary OA-DLBCL subgroup,12 patients(50%)presented with advanced disease(Ann Arbor stage IIIE–IV),and 16 patients(66%)were classified as T4 disease according to the tumor-node-metastasis(TNM)staging system.The mean final visual acuity was 1.72±1.10 in the primary group and 0.90±1.18 in the secondary group.The 5-year OS rate for the entire cohort was 27.7%.Multivariate analysis identified five factors significantly associated with poor survival outcomes:epiphora[adjusted hazard ratio(aHR),36.95],atherosclerotic cardiovascular disease(aHR,10.08),human immunodeficiency virus(HIV)infection(aHR,12.47),M1 stage(aHR,6.99),and secondary OA-DLBCL(aHR,6.03;all P<0.05).The median OS was 1.68y for primary OA-DLBCL and 1.12y for secondary OA-DLBCL.CONCLUSION:A substantial proportion of patients with primary OA-DLBCL present with advanced-stage disease at diagnosis.Epiphora,atherosclerotic cardiovascular disease,HIV infection,M1 stage,and secondary OA-DLBCL are independent prognostic factors for poor survival outcomes.These findings emphasize the urgent need for optimized therapeutic strategies and early screening protocols to improve the management of OA-DLBCL,particularly in developing countries.
基金supported by the DGIST start-up funds from the Ministry of Science and ICT(2024010330)a National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(No.RS-2024-00351442)(to TWK).
文摘Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.
基金This work is supported by the National Natural Science Foundation of China[71571144,71401134,71171164,11701406]The Natural Science Basic Research Program of Shaanxi Province[2015JM1003]The Program of international Cooperation and Exchanges in Science and Technology Funded by Shaanxi Province[2016KW-033].
文摘In this paper, we proposed a dynamic stress–strength model for coherent system. It is supposedthat the system consists of n components with initial random strength and each component issubjected to random stresses. The stresses, applied repeatedly at random cycle times, will causethe degradation of strength. In addition, the number of cycles in an interval is assumed to followa Poisson distribution. In the case of the strength and stress random variables following exponential distributions, the expression for the reliability of the proposed dynamic stress–strengthmodel is derived based on survival signature. The reliability is estimated by using the best linearunbiased estimation (BLUE). Considering the Type-II censored failure times, the best linear unbiased predictors (BLUP) for the unobserved coherent system failure times are developed basedon the observed failure times. Monte Carlo simulations are performed to compare the BLUE ofparameters with different values and compute the BLUP. A real data set is also analysed for anillustration of the findings.
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
基金Supported by National Natural Science Foundation of China,No.82002515,No.82273025 and No.82203460China Postdoctoral Science Foundation,No.2022TQ0070 and No.2022M710759Shanghai Municipal Commission of Science and Technology,No.22JC1403003,No.22XD1402200,No.19140901902 and No.22S31903800.
文摘BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteristics and clinical results of oesophageal GISTs.AIM To investigate endoscopic treatment effective of oesophageal GISTs.METHODS It was retrospective research that collected 32 patients with oesophageal GISTs treated by endoscopic resection(ER)between January 2012 and January 2023 in two Hospital.Clinicopathologic,endoscopic records,and follow-up data were collected and analysed.RESULTS Thirty-one patients underwent en bloc resection and 24(75.0%)lesions underwent R0 resection.The size of GISTs was 2.12±1.88 cm.The overall complication rate was 25.0%,including hydrothorax and post-endoscopic submucosal dissection electrocoagulation syndrome.The mean mitotic index was 3.34±5.04(median,1.50;range,1.00-4.00).Eighteen(56.3%),6(18.8%),2(6.3%),and 6(18.8%)patients were identified as very low,low,intermediate,and high risk,respectively.Three patients developed recurrence after a median follow-up of 64.69±33.13 months.The 5-year overall survival rate was 100%,and the disease-free survival rate was 90.6%.CONCLUSION ER is safe and effective for patients with low-risk oesophageal GISTs.Early detection of oesophageal GISTs is essential to achieve a favourable prognosis.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.
基金supported by grants from the National Natural Science Foundation of China(91959203,82272836 and 82373017)。
文摘Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.
文摘BACKGROUND Cholangiocarcinoma(CCA)comprises heterogeneous malignancies arising at different anatomical locations:Intrahepatic cholangiocarcinoma(IHCC),perihilar cholangiocarcinoma(PHCC),and distal cholangiocarcinoma(DCC).These subtypes exhibit distinct clinical behaviors,treatment approaches,and outcomes.Despite advances in surgical and adjuvant therapies,the prognostic implications of tumor location remain unclear and inconsistently reported.Understanding these variations is essential for personalized management and staging refinement.We hypothesized that the anatomical subtype of CCA significantly influences prognostic outcomes and pathological features.AIM To compare prognostic outcomes and clinicopathological characteristics among IHCC,PHCC,and DCC based on current evidence.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.PubMed,EMBASE,and the Cochrane Library were searched,yielding 11 eligible retrospective comparative studies involving 14484 patients(IHCC:6260;PHCC:6895;DCC:1329).Outcomes assessed included overall survival(OS),lymph node metastasis,neural invasion,and vascular invasion.Statistical analyses were performed using RevMan 5.3 and Stata 13.0.RESULTS DCC demonstrated the most favorable prognosis among all subtypes.Despite the highest lymph node metastasis rate(DCC:56.9%),it was associated with better OS than PHCC and IHCC.Vascular invasion was more prevalent in IHCC(OR=1.66,95%CI:1.22-2.28,P=0.001).OS comparisons showed no significant difference between PHCC and IHCC(HR=1.02,P=0.88),while DCC showed consistent trends toward better survival against both.CONCLUSION Anatomical subtype is a significant prognostic factor in CCA.DCC patients experience superior outcomes despite aggressive lymphatic spread,suggesting better resectability and surgical outcomes.These insights underscore the need for subtype-specific management strategies and future prospective validation.
基金Supported by Clinical Trials from the Third Affiliated Hospital of Soochow University,No.2024-156Changzhou Science and Technology Program,No.CJ20244017。
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and life-threatening cancer with increasing incidence worldwide.High Ki-67 risk stratification is closely associated with higher recurrence rates and worse outcomes following curative therapies in patients with HCC.However,the performance of radiomic and deep transfer learning(DTL)models derived from biparametric magnetic resonance imaging(bpMRI)in predicting Ki-67 risk stratification and recurrence-free survival(RFS)in patients with HCC remains limited.AIM To develop a nomogram model integrating bpMRI-based radiomic and DTL signatures for predicting Ki-67 risk stratification and RFS in patients with HCC.METHODS This study included 198 patients with histopathologically confirmed HCC who underwent preoperative bpMRI.Ki-67 risk stratification was categorized as high(>20%)or low(≤20%)according to immunohistochemical staining.Radiomic and DTL signatures were extracted from the T2-weighted and arterial-phase images and combined through a random forest algorithm to establish radiomic and DTL models,respectively.Multivariate regression analysis identified clinical risk factors for high Ki-67 risk stratification,and a predictive nomogram model was developed.RESULTS A nonsmooth margin and the absence of an enhanced capsule were independent factors for high Ki-67 risk stratification.The area under the curve(AUC)of the clinical model was 0.77,while those of the radiomic and DTL models were 0.81 and 0.87,respectively,for the prediction of high Ki-67 risk stratification,and the nomogram model achieved a better AUC of 0.92.The median RFS times for patients with high and low Ki-67 risk stratification were 33.00 months and 66.73 months,respectively(P<0.001).Additionally,patients who were predicted to have high Ki-67 risk stratification by the nomogram model had a lower median RFS than those who were predicted to have low Ki-67 risk stratification(33.53 vs 66.74 months,P=0.007).CONCLUSION Our developed nomogram model demonstrated good performance in predicting Ki-67 risk stratification and predicting survival outcomes in patients with HCC.
基金supported by the Young Talents Program of Jiangsu Cancer Hospital(Grant No.QL201802)the Science and Technology Development Fund of Jiangsu Cancer Hospital(Grant No.ZL202105).
文摘The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.
文摘BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.
文摘Rectal neuroendocrine tumors(r-NETs)are the second most common type of neuroendocrine tumor in the gastrointestinal tract,with an increase in incidence in the last decades.They are low-grade tumors and,given their low risk of meta-stasis,current guidelines recommend endoscopic resection for small lesions.The GATIS predicting score,proposed by Zeng et al,represents an innovative model designed to predict individualized survival outcomes for patients with r-NETs,analyzing the relationship between clinicopathological features and patient prog-noses.The authors identified tumor grade,T stage,tumor size,age,and progno-stic nutritional index as key prognostic factors,demonstrating that the GATIS Score provides a more accurate prognosis assessment compared to the World Health Organization classification or the tumor-node-metastasis staging system.Nevertheless,further larger prospective studies are necessary,and the scientific community's efforts in this context should be directed toward developing interna-tional multicentric prospective studies,with the ultimate aim of accurately de-fining and understanding the behavior of these conditions.
