Single incision laparoscopic surgery for hepatocellular carcinoma

Single incision laparoscopic liver resection(SILLR)is the most recent develop-ment in the laparoscopic approach to the liver.SILLR for hepatocellular carci-noma(HCC)has developed much more slowly than multiport LLR.So far,195 patients completed SILLR for HCC.In this paper,we reviewed all published papers about SILLR for HCC and discussed the feasibility of the SILLR,peri and postoperative findings,tricks of patient selection and whether SILLR compromise the oncological principles.

Benefits and drawbacks of radiofrequency ablation via percutaneous or minimally invasive surgery for treating hepatocellular carcinoma

The management of early stage hepatocellular carcinoma(HCC)presents significant challenges.While radiofrequency ablation(RFA)has shown safety and effectiveness in treating HCC,with lower mortality rates and shorter hospital stays,its high recurrence rate remains a significant impediment.Consequently,achieving improved survival solely through RFA is challenging,particularly in retrospective studies with inherent biases.Ultrasound is commonly used for guiding percutaneous RFA,but its low contrast can lead to missed tumors and the risk of HCC recurrence.To enhance the efficiency of ultrasound-guided percutaneous RFA,various techniques such as artificial ascites and contrast-enhanced ultrasound have been developed to facilitate complete tumor ablation.Minimally invasive surgery(MIS)offers advantages over open surgery and has gained traction in various surgical fields.Recent studies suggest that laparoscopic intraoperative RFA(IORFA)may be more effective than percutaneous RFA in terms of survival for HCC patients unsuitable for surgery,highlighting its significance.Therefore,combining MIS-IORFA with these enhanced percutaneous RFA techniques may hold greater significance for HCC treatment using the MIS-IORFA approach.This article reviews liver resection and RFA in HCC treatment,comparing their merits and proposing a trajectory involving their combination in future therapy.

Reassessment of palliative surgery in conversion therapy of previously unresectable hepatocellular carcinoma: Two case reports and review of literature

BACKGROUND Most patients with hepatocellular carcinoma(HCC)have lost the opportunity for direct surgery at the time of diagnosis.Transarterial chemoembolization(TACE)combined with immune checkpoint inhibitors or tyrosine kinase inhibitors(TKI)can partially transform some unresectable HCC and improve the prognosis ef-fectively.However,based on the promising prospects of combined targeted and immunotherapy for the effective treatment of HCC,the positive role of palliative surgery in the conversion treatment of advanced HCC urgently needs further in-tensive re-assessment.CASE SUMMARY In this study,we describe two successful cases of"conversion therapy for un-resectable HCC"achieved mainly by palliative surgery combined with TACE plus immunotherapy and TKIs.A 48-year-old patient with newly diagnosed HCC,presenting with a 6-cm mass in the segment VII/VIII of the right liver with mul-tiple intrahepatic metastases,could not undergo one-stage radical surgical resection.He underwent palliative surgery with radiofrequency of metastatic lesions and the palliative resection of the primary mass,and received subsequent TACE treatments twice in the early postoperative period(2 weeks and 6 weeks),in addition to targeted and immune combination therapy with sintilimab injection and oral lenvatinib.No evidence of recurrence was observed during the 11-month follow-up period after surgery.The other patient was a 47-year-old patient with massive HCC(18 cm×15 cm×4.5 cm)in the left liver with severe cirrhosis.The left portal branch was occluded and a tumor thrombus formed,and the tumor partly involved the middle hepatic vein.The patient underwent palliative surgery of left hemihepatectomy(including resection of the middle hepatic vein)for HCC,followed by three TACE procedures and oral TKIs 2 weeks after surgery.Six months later,the re-examination via computed tomography revealed no tumour activity in the remaining right liver,while magnetic resonance imaging revealed slight local tumor enhancement in the caudate lobe of the liver considered,TACE was performed once again,and during the next follow-up of 10 months did not reveal new intrahepatic lesions or distant metastases.CONCLUSION These cases demonstrate that the addition of palliative surgery to conversion therapy in a selected population with a high tumor burden could benefit patients with initially unresectable HCC.

New direction for surgery:Super minimally invasive surgery

The top goal of modern medicine is treating disease without destroying organ structures and making patients as healthy as they were before their sickness.Minimally invasive surgery(MIS)has dominated the surgical realm because of its lesser invasiveness.However,changes in anatomical structures of the body and reconstruction of internal organs or different organs are common after traditional surgery or MIS,decreasing the quality of life of patients post-operation.Thus,I propose a new treatment mode,super MIS(SMIS),which is defined as“curing a disease or lesion which used to be treated by MIS while preserving the integrity of the organs”.In this study,I describe the origin,definition,operative channels,advantages,and future perspectives of SMIS.

Bariatric surgery and diabetes:Current challenges and perspectives

Diabetes mellitus(DM)and obesity have become public issues of global concern.Bariatric surgery for the treatment of obesity combined with type 2 DM has been shown to be a safe and effective approach;however,there are limited studies that have systematically addressed the challenges of surgical treatment of obesity combined with DM.In this review,we summarize and answer the most pressing questions in the field of surgical treatment of obesity-associated DM.I believe that our insights will be of great help to clinicians in their daily practice.

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Artificial Intelligence and Computer Vision during Surgery: Discussing Laparoscopic Images with ChatGPT4—Preliminary Results

Introduction: Ultrafast latest developments in artificial intelligence (ΑΙ) have recently multiplied concerns regarding the future of robotic autonomy in surgery. However, the literature on the topic is still scarce. Aim: To test a novel AI commercially available tool for image analysis on a series of laparoscopic scenes. Methods: The research tools included OPENAI CHATGPT 4.0 with its corresponding image recognition plugin which was fed with a list of 100 laparoscopic selected snapshots from common surgical procedures. In order to score reliability of received responses from image-recognition bot, two corresponding scales were developed ranging from 0 - 5. The set of images was divided into two groups: unlabeled (Group A) and labeled (Group B), and according to the type of surgical procedure or image resolution. Results: AI was able to recognize correctly the context of surgical-related images in 97% of its reports. For the labeled surgical pictures, the image-processing bot scored 3.95/5 (79%), whilst for the unlabeled, it scored 2.905/5 (58.1%). Phases of the procedure were commented in detail, after all successful interpretations. With rates 4 - 5/5, the chatbot was able to talk in detail about the indications, contraindications, stages, instrumentation, complications and outcome rates of the operation discussed. Conclusion: Interaction between surgeon and chatbot appears to be an interesting frontend for further research by clinicians in parallel with evolution of its complex underlying infrastructure. In this early phase of using artificial intelligence for image recognition in surgery, no safe conclusions can be drawn by small cohorts with commercially available software. Further development of medically-oriented AI software and clinical world awareness are expected to bring fruitful information on the topic in the years to come.

Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images

Accurate segmentation of oral surgery-related tissues from cone beam computed tomography(CBCT)images can significantly accelerate treatment planning and improve surgical accuracy.In this paper,we propose a fully automated tissue segmentation system for dental implant surgery.Specifically,we propose an image preprocessing method based on data distribution histograms,which can adaptively process CBCT images with different parameters.Based on this,we use the bone segmentation network to obtain the segmentation results of alveolar bone,teeth,and maxillary sinus.We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks.The tooth segmentation results can obtain the order information of the dentition.The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods.Its average Dice scores on the tooth,alveolar bone,maxillary sinus,and mandibular canal segmentation tasks were 96.5%,95.4%,93.6%,and 94.8%,respectively.These results demonstrate that it can accelerate the development of digital dentistry.

Construction and validation of somatic mutation-derived long noncoding RNAs signatures of genomic instability to predict prognosis of hepatocellular carcinoma

BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.

Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

Is recovery enhancement after gastric cancer surgery really a safe approach for elderly patients?

BACKGROUND This study aimed to evaluate the safety of enhanced recovery after surgery(ERAS)in elderly patients with gastric cancer(GC).AIM To evaluate the safety of ERAS in elderly patients with GC.METHODS The PubMed,EMBASE,and Cochrane Library databases were used to search for eligible studies from inception to April 1,2023.The mean difference(MD),odds ratio(OR)and 95%confidence interval(95%CI)were pooled for analysis.The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores.We used Stata(V.16.0)software for data analysis.RESULTS This study consists of six studies involving 878 elderly patients.By analyzing the clinical outcomes,we found that the ERAS group had shorter postoperative hospital stays(MD=-0.51,I2=0.00%,95%CI=-0.72 to-0.30,P=0.00);earlier times to first flatus(defecation;MD=-0.30,I²=0.00%,95%CI=-0.55 to-0.06,P=0.02);less intestinal obstruction(OR=3.24,I2=0.00%,95%CI=1.07 to 9.78,P=0.04);less nausea and vomiting(OR=4.07,I2=0.00%,95%CI=1.29 to 12.84,P=0.02);and less gastric retention(OR=5.69,I2=2.46%,95%CI=2.00 to 16.20,P=0.00).Our results showed that the conventional group had a greater mortality rate than the ERAS group(OR=0.24,I2=0.00%,95%CI=0.07 to 0.84,P=0.03).However,there was no statistically significant difference in major complications between the ERAS group and the conventional group(OR=0.67,I2=0.00%,95%CI=0.38 to 1.18,P=0.16).CONCLUSION Compared to those with conventional recovery,elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.

Albumin–bilirubin grade as a predictor of survival in hepatocellular carcinoma patients with thrombocytopenia

BACKGROUND The models for assessing liver function,mainly the Child–Pugh(CP),albuminbilirubin(ALBI),and platelet–ALBI(PALBI)classifications,have been validated for use in estimating the prognosis of hepatocellular carcinoma(HCC)patients.However,thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC.AIM To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients.METHODS A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed.Preoperative scores on the CP,ALBI and PALBI classifications were estimated accordingly.Kaplan–Meier curves with logrank tests and Cox regression models were used to explore the significant factors associated with overall survival(OS)and recurrence-free survival(RFS).RESULTS The preoperative platelet counts were significantly different among the CP,ALBI and PALBI groups.After a median follow-up of 28 mo,39.3%(53/135)of the patients experienced postoperative recurrence,and 36.3%(49/135)died.Univariate analysis suggested thatα-fetoprotein levels,tumor size,vascular invasion,and ALBI grade were significant predictors of OS and RFS.According to the multivariate Cox regression model,ALBI was identified as an independent prognostic factor.However,CP and PALBI grades were not statistically significant prognostic indicators.CONCLUSION The ALBI grade,rather than CP or PALBI grade,is a significant prognostic indicator for thrombocytopenic HCC patients.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Bioinformatics analysis and experimental validation of cystathionine-gamma-lyase as a potential prognosis biomarker in hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.