Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients

Objective The activities and products of carbohydrate metabolism are involved in key processes of cancer.However,its relationship with hepatocellular carcinoma(HCC)is unclear.Methods The cancer genome atlas(TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases.Differentially expressed genes(DEGs)between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes(CRGs)to obtain differentially expressed CRGs(DE-CRGs).Then,univariate Cox and least absolute shrinkage and selection operator(LASSO)analyses were applied to identify risk model genes,and HCC samples were divided into high/low-risk groups according to the median risk score.Next,gene set enrichment analysis(GSEA)was performed on the risk model genes.The sensitivity of the risk model to immunotherapy and chemotherapy was also explored.Results A total of 8 risk model genes,namely,G6PD,PFKFB4,ACAT1,ALDH2,ACYP1,OGDHL,ACADS,and TKTL1,were identified.Moreover,the risk score,cancer status,age,and pathologic T stage were strongly associated with the prognosis of HCC patients.Both the stromal score and immune score had significant negative/positive correlations with the risk score,reflecting the important role of the risk model in immunotherapy sensitivity.Furthermore,the stromal and immune scores had significant negative/positive correlations with risk scores,reflecting the important role of the risk model in immunotherapy sensitivity.Eventually,we found that high-/low-risk patients were more sensitive to 102 drugs,suggesting that the risk model exhibited sensitivity to chemotherapy drugs.The results of the experiments in HCC tissue samples validated the expression of the risk model genes.Conclusion Through bioinformatic analysis,we constructed a carbohydrate metabolism-related risk model for HCC,contributing to the prognosis prediction and treatment of HCC patients.

Marine biological injuries and their medical management:A narrative review

The marine environment can be extremely dangerous,and the harm caused by marine organisms when they contact the human body can be especially harmful,even deadly.Contact includes stings,bites,wounds,and consumption as food.In this article,the characteristics of the common marine biological injuries are summarized,the major marine organisms causing damage in China’s marine waters are described,and injury prevention and treatment methods are discussed.

Bcl-2 expression is a poor predictor for hepatocellular carcinoma prognosis of andropause-age patients

Objective: The expression of B-cell lymphoma 2(Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma(HCC) patients was examined to verify the high incidence of HCC in males.Methods: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68 females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive value of Bcl-2 in HCC patients.Results: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer median survival time and recurrence time than those with lower levels. However, no significant differences in outcomes were found between different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2expression showed poorer predictive efficiency in the 45–49 and 55–60 age groups in andropause-age patients compared with other age groups. Bcl-2 was an independent prognostic factor for both overall survival(P < 0.0001) and recurrence time(P =0.0001) in male patients. After excluding male patients in the 45–60 age group, the predictive efficiency was enhanced(n = 147,OS, P = 0.0002, TTR, P < 0.0001).Conclusions: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also be regulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiency when androgen levels vary dramatically(andropause age).

Biomarkers for response to immunotherapy in hepatobiliary malignancies

Background:The advent of immune checkpoint inhibitors(ICIs)has revolutionized the therapeutic options of hepatobiliary malignancies.However,the clinical benefit provided by immunotherapy seems limited to a small subgroup of patients with hepatobiliary malignancies.The identification of reliable predictors of the response to immunotherapy is urgently needed.Data sources:Literature search was conducted in Pub Med for relevant articles published up to May 2022.Information of clinical trials was obtained from https://clinicaltrials.gov/.Results:Biomarkers for ICI response of hepatobiliary malignancies remain in the exploration stage and lack compelling evidence.Tumor programmed death-ligand 1(PD-L1)expression is the most widely studied biomarker in hepatocellular carcinoma(HCC)and biliary tract cancers(BTCs),but there are conflicting results on its predictive potential.Tumor mutational burden(TMB)is generally low both in HCC and BTCs,and the clinical trials of TMB are rare in hepatobiliary malignancies.Promisingly,mismatch repair deficiency(dMMR)/high microsatellite instability(MSI-H)may be a predictive biomarker of response to antiPD-1 therapy in BTCs.Furthermore,some emerging biomarkers,such as gut microbiota,show predictive potential in the preliminary studies.Radiomics and liquid-biopsy biomarkers,including circulating tumor cells,circulating tumor DNA(ct DNA)and exosomal PD-L1 provide a quick and non-invasive approach for monitoring the ICI response,showing a new promising direction.Conclusions:Multiple potential biomarkers for predicting ICI response of hepatobiliary malignancies have been explored and tried to apply in clinic.Yet there is no robust evidence to prove their clinical value in predicting immunotherapeutic response for patients with hepatobiliary malignancies.The identification of predictors for response to ICIs is an urgent need and major challenge.Further studies are warranted to validate the role of emerging biomarkers in predicting immunotherapeutic responses.

Local events-based fast RTM surface-offset gathers via dip-guided interpolation

Reverse Time Migration(RTM)Surface Ofset Gathers(SOGs)are demonstrated to deliver more superior residual dip information than ray-based approaches.It appears more powerful in complex geological settings,such as salt areas.Still,the computational cost of constructing RTM SOGs is a big challenge in applying it to 3D feld data.To tackle this challenge,we propose a novel method using dips of local events as a guide for RTM gather interpolation.The residual-dip information of the SOGs is created by connecting local events from depth-domain to time-domain via ray tracing.The proposed method is validated by a synthetic experiment and a feld example.It mitigates the computational cost by an order of magnitude while producing comparable results as fully computed RTM SOGs.

A Possible 250s X-Ray Quasi-periodicity in the Fast Blue Optical Transient AT2018cow

The fast blue optical transients(FBOTs)are a new population of extragalactic transients of unclear physical origin.A variety of mechanisms has been proposed including failed supernova explosion,shock interaction with a dense medium,young magnetar,accretion onto a compact object and stellar tidal disruption event,but none is conclusive.Here we report the discovery of a possible X-ray quasi-periodicity signal with a period of~250 s(at a significance level of 99.76%)in the brightest FBOT AT2018cow through the analysis of XMM-Newton/PN data.The signal is independently detected at the same frequency in the average power density spectrum from data taken from the Swift telescope,with observations covering from 6 to 37 days after the optical discovery,though the significance level is lower(94.26%).This suggests that the quasi-periodic oscillation(QPO)frequency may be stable over at least 1.1×10^(4)cycles.Assuming the~250 s QPO to be a scaled-down analog of that typically seen in stellar mass black holes,a black hole mass of~103–10^(5)solar masses could be inferred.The overall X-ray luminosity evolution could be modeled with a stellar tidal disruption by a black hole of~10^(4)solar masses,providing a viable mechanism to produce AT2018cow.Our findings suggest that other bright FBOTs may also harbor intermediate-mass black holes.

The application of real-time indocyanine green fluorescence cholangiography in laparoscopic living donor left lateral sectionectomy

Background:The judgment of the division point of the bile duct has always been one of the difficulties of laparoscopic left lateral sectionectomy(LLLS).The purpose of this study was to assess the effects of indocyanine green(ICG)fluorescence cholangiography during LLLS on the occurrence of biliary complications in both donors and recipients.The optimal dose and injection time of ICG were also investigated.Methods:This is a retrospective cohort study.From October 2016 to December 2022,the clinical data of 103 donors who underwent LLLS and relevant recipients were retrospectively analyzed.According to whether ICG fluorescence cholangiography was used,they were divided into a non-ICG group(n=46)and an ICG group(n=57).Biliary complications were observed and the optimal dose and injection time of ICG were explored.Results:Three donors in the non-ICG group suffered from bile leakage.Four grafts had multiple bile duct openings and biliary complications were observed in the relevant recipients who received these grafts in the non-ICG group.Two recipients had bile leakage,and the other two had biliary stenosis.There was no biliary complications both in donors and recipients in the ICG group.The fluorescence intensity of the liver was 108.1±17.6 at a dose of 0.004 mg/kg 90 minutes after injection,significantly weaker than that at 0.05 mg/kg 30 minutes(200.3±17.6,P=0.001)and 90 minutes after injection(140.2±15.4,P=0.001).The fluorescence intensity contrast value at a dose of 0.004 mg/kg was stronger than that at 0.05 mg/kg,both measured 90 minutes after injection(0.098±0.032 vs.0.078±0.022,P=0.021).Conclusions:ICG fluorescence cholangiography is safe and feasible in LLLS.It reduces biliary complications in both donors and recipients.The optimal ICG dose was 0.004 mg/kg,and 90 minutes after injection was the best observation time.ICG fluorescence cholangiography is recommended for routine use in LLLS.

Expert consensus-promoting clinical excellence and ultimately benefitting patients

Evidence-based medicine serves as the cornerstone of modern healthcare.Based on current evidence in the field of evidence-based medicine,a team of authoritative experts in the industry engages in comprehensive discussions to develop expert consensus,following standardized procedures.The consensus serves as a foundation for clinical decision-making.However,the abundance of expert consensus varies in quality,and some viewpoints even contradict each other,leading to confusion in clinical decision-making.

Mass Casualty Incident Primary Triage Methods in China

Objective：To evaluate the technical characteristics and application of mass casualty incident （MCI） primary triage （PT） methods applied in China.Data Sources：Chinese literature was searched by Chinese Academic Journal Network Publishing Database （founded in June 2014）.The English literature was searched by PubMed （MEDLINE） （1950 to June 2014）.We also searched Official Websites of Chinese Central Government＇s （http：//www.gov.cn/）,National Health and Family Planning Commission of China （http：//www.nhfpc.gov.cn/）,and China Earthquake Information （http：//www.csi.ac.cn/）.Study Selection：We included studies associated with mass casualty events related to China,the PT applied in China,guidelines and standards,and application and development of the carding PT method in China.Results：From 3976 potentially relevant articles,22 met the inclusion criteria,20 Chinese,and 2 English.These articles included 13 case reports,3 retrospective analyses of MCI,two methods introductions,three national or sectoral criteria,and one simulated field testing and validation.There were a total of 19 kinds ofMCI PT methods that have been reported in China from 1950 to 2014.In addition,there were 15 kinds of PT methods reported in the literature from the instance of the application.Conclusions：The national and sectoral current triage criteria are developed mainly for earthquake relief.Classification is not clear.Vague criteria （especially between moderate and severe injuries） operability are not practical.There are no triage methods and research for children and special populations.There is no data and evidence supported triage method.We should revise our existing classification and criteria so it is clearer and easier to be grasped in order to build a real,practical,and efficient PT method.

Efficacy of Postoperative Hormone Replacement Therapy on Prognosis of Patients with Serous Ovarian Carcinoma

Background： Ovarian cancer is the most common cause of gynecological cancer-associated death. Iatrogenic menopause might adversely affect the quality of life and health outcomes in young female cancer survivors. We evaluated whether postoperative hormone replacement therapy （HRT） had a negative influence on the progression-free survival （PFS） of patients with papillary serous ovarian cancer （SOC）. Methods： We retrospectively reviewed the medical records of patients with papillary SOC, treated from January 1980 to December 2009, who suffered from menopause with or without HRT. Clinical characteristics of patients were compared between the two groups （HRT and non-HRT）. Blood samples were collected from all the participants to detect serum cancer antigen （CA） 125. Hazard ratios with 95% confidential intervals for each variable were calculated by univariable and multivariable conditional Logistic regression analyses. Results： Among 112 identified patients, 31 were HRT users and 81 were not. The two groups did not significantly differ in median age at diagnosis （t = 0.652, P = 0.513）, International Federation of Gynecology and Obstetrics （FIGO） stage （X2 = 0.565, P = 0.754）, differentiation （X2 = 1.728, P = 0.422）, resection status （X2 = 0.070, P = 0.791）, relapse （X2 = 0.109, P = 0.741）, chemotherapy course （t = -1.079, P - 0.282）, follow-up interval （t = 0.878, P = 0.382）, or PFS （t = 0.580, P = 0.562）. Median Kupperman score at the onset of HRT was 30.81 and 12.19 after the therapy （t： 3.302, P = 0.001）. According to the analysis, the strongest independent variables in predicting PFS were FIGO stage and disease that was not optimally debulked. Conclusions： Postoperative HRT is not a prognostic factor for PFS of patients with papillary SOC. However, multicenter studies are needed to verify and extend our findings.