International consensus guidelines on robotic pancreatic surgery in 2023

Background:With the rapid development of robotic surgery,especially for the abdominal surgery,robotic pancreatic surgery(RPS)has been applied increasingly around the world.However,evidence-based guidelines regarding its application,safety,and efficacy are still lacking.To harvest robust evidence and comprehensive clinical practice,this study aims to develop international guidelines on the use of RPS.Methods:World Health Organization(WHO)Handbook for Guideline Development,GRADE Grid method,Delphi vote,and the AGREE-II instrument were used to establish the Guideline Steering Group,Guideline Development Group,and Guideline Secretary Group,formulate 19 clinical questions,develop the recommendations,and draft the guidelines.Three online meetings were held on 04/12/2020,30/11/2021,and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts.All the experts focusing on minimally invasive surgery from America,Europe and Oceania made great contributions to this consensus guideline.Results:After a systematic literature review 176 studies were included,19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence.Conclusions:The international RPS guidelines can guide current practice for surgeons,patients,medical societies,hospital administrators,and related social communities.Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

The global burden of fatty liver disease:the major impact of China

Due to the energy-dense but nutrient-deficient diets,sedentary lifestyle and lack of exercise as well as an aging population,the prevalence and incidence of overweight/obesity/sarcopenic obesity,type 2 diabetes mellitus(T2DM),metabolic syndrome and their related non-alcoholic fatty liver disease(NAFLD)have been increasing globally in the last two decades.In Europe and the United States,NAFLD has become the second leading cause of end-stage liver disease and liver transplantation(1).Worse still,the onset age of NAFLD is becoming younger tendency.Although the new nomenclature of metabolic dysfunction-associated fatty liver disease(MAFLD)has been proposed for 3 years,MAFLD is not equivalent to NAFLD,and few epidemiologic investigations on MAFLD to date.Therefore,this invited editorial is focus on the global epidemiology of NAFLD and the major impact on China.

Insights from Seoul National University Hospital’s experience: a systematic review of pure laparoscopic donor hepatectomy progression

Following its initial execution in November 2015,pure laparoscopic donor hepatectomy(PLDH)has gained acceptance as a conventional practice at Seoul National University Hospital(SNUH).It is noteworthy that a significant proportion of cases entail full right hepatectomies,which are acknowledged to be technically demanding.As expertise and knowledge have been accrued,the pure laparoscopic technique has been extended to encompass liver recipients as a viable option in SNUH.The aim of this review is to present the developmental progression of PLDH,with a focus on pure laparoscopic donor right hepatectomy(PLDRH),at SNUH.This includes the standardization process,which can be achieved by sharing the hospital’s accumulated experience and previous reports.Various types of graft,including full right,left,left lateral section,and monosegment,were procured by pure laparoscopic technique.The criteria for selection were expanded to include donors with variations in the anatomy of the portal vein and bile duct.Additionally,the procedure of PLDRH was determined to be safe and viable for donors with high body mass index and larger graft weight.In conclusion,this review demonstrates the alterations implemented throughout our evolution from restricted to inclusive criteria for donor selection,leading to a complete shift from open surgery to pure laparoscopic procedures in donor hepatectomy and eventually pure laparoscopic living donor liver transplantation(LDLT)in recipient.

Microbial influence on liver regeneration: understanding gut microbiota and hepatic recovery post partial hepatectomy

The liver is a unique solid organ with a regenerative capacity that is an important factor in the outcome of partial hepatectomy(PHx)performed to treat life-threating liver diseases(1-3).Multiple intrahepatic and extrahepatic signaling pathways synergistically regulate liver regeneration to restore typical liver functionality and thereby promote maximal life expectancy(2,4).Among the extrahepatic factors,gut metabolites are pivotal signaling molecules that affect the regulation of liver regeneration(5,6).Interestingly,dysbiosis of the gut microbiota due to disease or treatment strategies can influence liver regeneration negatively and delay recovery(7-9).In this empirical study,Yin et al.

Management of hepatocellular carcinoma recurrence after liver surgery and thermal ablations:state of the art and future perspectives

Despite the improvements in surgical and medical therapy for hepatocellular carcinoma(HCC),recurrence still represents a major issue.Up to 70%of patients can experience HCC recurrence after liver resection(LR),as well as 20%of them even after liver transplantation(LT).The patterns of recurrence are different according to both the time and the location.Similarly,the risk factors and the management can change not only according to these patterns,but also according to the underlying liver condition and to the first treatment performed.Deep knowledge of such correlation is fundamental,since prevention and effective management of recurrence are undoubtedly the most important strategies to improve the outcomes of HCC treatment.Without adjuvant therapy,maintaining very close monitoring during the first 2 years in order to diagnose curable recurrence and continue this monitoring beyond 5 years because late recurrences exist,remains our only possibility today.Surgery represents the cornerstone treatment for HCC,including both LT and LR.However,new interesting therapeutic opportunities are coming from immunotherapy that has shown encouraging results also in the adjuvant setting.In such a complex and evolutionary scenario,the aim of this review is to summarize current strategies for the management of HCC recurrence,focusing on the different possible scenarios,as well as on future perspectives.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study

Background:Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma(HCC)patients.The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure(PHLF)remains poorly defined.This study aimed to construct and validate a combined pre-and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center’s data.Methods:Consecutive HCC patients who underwent hepatectomy between May 18,2019 and Dec 19,2020 were enrolled at five tertiary hospitals.Preoperative cirrhotic severity scoring(CSS)and intra-operative direct liver stiffness measurement(DSM)were performed to correlate with the Laennec histopathological grading system.The performances of the pre-operative nomogram and combined pre-and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF.Results:For 327 patients in this study,histopathological studies showed the rates of HCC patients with no,mild,moderate,and severe cirrhosis were 41.9%,29.1%,22.9%,and 6.1%,respectively.Either CSS or DSM was closely correlated with histopathological stages of cirrhosis.Thirty-three(10.1%)patients developed PHLF.The 30-and 90-day mortality rates were 0.9%.Multivariate regression analysis showed four pre-operative variables[HBV-DNA level,ICG-R15,prothrombin time(PT),and CSS],and one intra-operative variable(DSM)to be independent risk factors of PHLF.The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin.The combined pre-and intra-operative nomogram was constructed by adding the intra-operative DSM.The pre-operative nomogram was better than the conventional models in predicting PHLF.The prediction was further improved with the combined pre-and intra-operative nomogram.Conclusions:The combined pre-and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram.

Evaluation of the economic impact of the robotic approach in major and postero-superior segment liver resections: a multicenter retrospective analysis

Background:Economic impact of robotic liver surgery(RLS)is still a debated issue due to the heterogeneity of liver resections considered and the lack of a rigorous methodology.Therefore,the aim of this study is to perform a time-driven activity-based costing(TD-ABC)comparing the costs of RLS,laparoscopic liver surgery(LLS)and open liver surgery(OLS)in the context of complex liver resections and to compare short term perioperative outcomes.Methods:The institutional databases of two Italian high volume hepatobiliary centres were retrospectively reviewed from February 2021 to April 2022.Patients submitted to major hepatectomies or postero-superior liver resections were selected and divided into three groups according to the approach scheduled(RLS,LLS and OLS)and compared.Major contributors of perioperative expenses were calculated using the TD-ABC model and accurately quantifying each unit resource consumed per patient and the time spent performing each activity.A primary intention-to-treat analysis(ITT-A)including conversions in the RLS and LLS groups was performed.Results:Forty-seven RLS,101 LLS and 124 OLS were collected.LLS and RLS showed reduced blood loss,morbidity,mortality and hospital stay compared with open.A trend towards reduced conversion rate in RLS compared to LLS was registered.Total costs associated with RLS were estimated at€10,637 vs.€9,543 for LLS and vs.€13,960 for OLS.The higher intraoperative costs associated with RLS(+153.3%vs.OLS and+148.2%vs.LLS,P<0.001),primarily related to surgical equipment expenses,were slightly offset by the postoperative savings(−56.0%vs.OLS and−29.4%vs.LLS,P<0.001)resulting from significantly reduced hospital stays.Conclusions:RLS offers economic advantages over OLS,as initial higher costs are offset by better perioperative outcomes.The evolving robotic marketplace is expected to drive down RLS costs,promoting widespread adoption in minimally invasive procedures.Despite its higher costs than LLS,RLS’s ability to enhance minimally invasive feasibility makes it a preferred choice for complex cases,reducing the need for conversions.

Treatment of portal vein thrombosis in cirrhosis with anticoagulation-more than meets the eye?

Portal vein thrombosis(PVT)is a common complication in patients with advanced chronic liver disease(i.e.,cirrhosis).In contrast to other thrombotic diseases,PVT in patients with cirrhosis is frequently asymptomatic and discovered incidentally during routine imaging procedures.There is ongoing debate on whether all patients with PVT require treatment as it is unclear whether PVT is a relatively innocent bystander or whether PVT worsens disease progression(1).Treatment may be required in patients with>50%occlusion of the portal vein who are transplant candidates to avoid thrombosis progression that may hinder a future liver transplantation or cause progression of portal hypertension(2).Current treatment consists of therapeutic anticoagulation with vitamin K antagonists,heparins,or direct oral anticoagulants.Although anticoagulant therapy for cirrhotic PVT is relatively safe,the efficacy is modest,with meta-analyses demonstrating recanalization of the portal vein in~30-40%of patients without anticoagulation,and~60-70%with anticoagulation(3,4).

3D laparoscopic anatomical hepatectomy guided by 2D real-time indocyanine green fluorescence imaging for hepatocellular carcinoma

Laparoscopic anatomical hepatectomy(LAH)for patients with hepatocellular carcinoma(HCC)has been advocated by many surgeons in the hope of producing better oncological outcomes.Two recent techniques,3D laparoscopic system and 2D real-time indocyanine green fluorescence imaging(r-ICG)guidance,are benefit for improving the operative precision of LAH in different aspects.However,these two techniques cannot be applied concomitantly because of the technical limitation.Although a new modern laparoscopic system with both 3D and indocyanine green(ICG)imaging mode has been designed,it has not been listed in many countries including China.Thus,we design a new procedure to perform the 3D LAH with 2D r-ICG guidance for HCCs with conventional laparoscopic systems.In this procedure,both 3D and 2D laparoscopic systems were used.A total of 11 patients with HCC received 3D laparoscopic right posterior sectionectomy(LRPS)with 2D r-ICG guidance.The right posterior Glissonian pedicle was clamped under the 3D vision.Then ICG solution was then intravenously administrated.The liver parenchyma was transected under the 3D vision and guided by 2D ICG vision simultaneously.There was no severe complications(Clavien-Dindo≥III)and operation related death.The 90-day mortality was also nil.By using this procedure,the advantages of two techniques,3D laparoscopic system and 2D r-ICG guidance,were combined so that LAH could be performed with more precision.However,it should be validated in more studies.

Early cholecystectomy cannot be regarded as a mortality risk factor in moderate and severe acute biliary pancreatitis

We read with great interest the article by Di Martino et al.(1)on the timing of cholecystectomy after moderately severe and severe acute biliary pancreatitis(ABP).In this retrospective study,the authors analyzed data from the MANCTRA-1 database.Of 5,304 patients,3,696 met the inclusion criteria(cholecystectomy performed and stage of pancreatitis known)and were included in the analysis.The aim of this study was to assess the impact of early cholecystectomy(EC)on morbidity and mortality in ABP,particularly in moderately severe and severe forms according to the modified Atlanta classification(2).EC was defined as removal of the gallbladder within 14 days of admission,and was compared with delayed cholecystectomy(DC).

Existing and emerging biomarkers in hepatocellular carcinoma:relevance in staging,determination of minimal residual disease,and monitoring treatment response:a narrative review

Background and Objective:With the development of novel active systemic therapies,the landscape of hepatocellular carcinoma(HCC)management is rapidly changing.However,HCC lacks sensitive and specific biomarkers to predict prognosis,monitor for minimal residual disease after locoregional therapy,and predict treatment response.In this review,we aim to summarize the best supporting evidence for refining existing,and development of novel biomarkers for staging,prognosis,determination of minimal residual disease and monitoring treatment response in HCC,focusing on those with evidence in clinical trials.Methods:PubMed and Embase databases were searched using the keywords;hepatocellular carcinoma,biomarker,minimal residual disease,surveillance,prognosis,staging,alpha-fetoprotein(AFP),liquid biopsy,treatment response,adjuvant,immunotherapy.Relevant clinical studies were included.Key Content and Findings:AFP remains the major workhorse as the most widely used biomarker in HCC,however,its lack of wide applicability due to the high proportion of patients with HCC who are AFP negative,limits its value throughout all stages of HCC management.Significant work has been done to combine AFP with other clinical and serologic factors to increase its accuracy and utility as a biomarkers.However,it is likely that other more novel biomarkers such as those obtained through liquid biopsy will provide the prognostic power necessary for applications such as detecting recurrence and predicting treatment response.Liquid biopsy provides not only a wealth of potential biomarkers including circulating tumor cells and cell-free RNA/DNA,but also the ability to examine the mutational characteristics of the tumor with next generation sequencing.While early evidence supports the potential impact of many new biomarkers,validation in large clinical trials is lacking.Conclusions:This review highlights the paucity of sensitive and specific,widely applicable biomarkers,throughout all phases of management of HCC and summarizes evidence on biomarkers currently in use,as well as those in development and validation.Inclusion of biomarker analysis through clinical trials in HCC is critical to development of optimal therapeutic regimens,and improve patient outcomes.

Molecular pathology and protein markers for pancreatic cancer:relevance in staging,in adjuvant therapy,in determination of minimal residual disease,and follow-up

The diagnosis and monitoring of disease through the detection of circulating protein biomarkers is a growing field in the practice of oncology.The search for more effective protein biomarkers to aid in the diagnosis and treatment of patients with pancreatic ductal adenocarcinoma(PDAC)remains a valuable area of study,given the aggressive and often occult nature of this malignancy.Liquid biopsies are attractive,as they offer a minimally invasive and cost-effective approach when compared to traditional biopsy methods and imaging modalities used for diagnosis and surveillance.Carbohydrate antigen(CA)19-9 is currently the most commonly used serum protein biomarker for the diagnosis and monitoring of patients with PDAC,but due to its sensitivity and specificity,its utility remains limited.In this review,we examine how circulating protein biomarkers are used in the diagnosis,prognostication,and surveillance of PDAC.We also highlight protein biomarkers that are currently under investigation that have the potential to enhance our ability to detect early-stage malignancies,predict response to therapy,and monitor for recurrence,but these markers require larger prospective validation studies before they can be widely implemented.Continued efforts to identify and validate novel biomarkers will be crucial for improving the management and outcomes of patients with this challenging disease.

Necessity of integrating statistical inference and clinical practice in developing clinical models: bias introduced by neoadjuvant chemotherapy

We read the article by Dr.Lam et al.(1).This article is a multicenter study involving Cox multivariable models with the least absolute shrinkage and selection operator(LASSO)to construct a survival prediction model for colorectal liver metastasis(CRLM)patients after hepatectomy.A total of 572 patients were enrolled,and two full models for overall survival(OS)and recurrence-free survival(RFS)consisting of the same eight novel variables were developed.This study provides a strong prediction for the survival of CRLM patients after hepatectomy,offering valuable guidance for clinical decision-making.However,after carefully reading this article,we have the following comments.

Beyond the Rex: an innovative meso-intrahepatic portal vein bypass for late-onset extrahepatic portal vein occlusion after living donor liver transplantation

The Meso-Rex bypass(MRB)is recognized as an effective treatment for portal hypertension secondary to extrahepatic portal vein occlusion(EHPVO)both in the pediatric and adult population,within or outside the context of liver transplantation.It is the preferred surgical treatment in most centers because not only does it addresses the portal hypertension,but also restores physiologic portal hepatopetal flow.However,the Rex recess,the landmark for this technique,may not be safely accessible in some patients.We present a 22-year-old male who underwent living donor liver transplant(LDLT)for neonatal hepatitis.He presented with variceal bleeding due to EHPVO at 13 years after transplant.Various endoscopic,radiologic,and surgical interventions were employed to address the recurrent gastrointestinal bleeding,but results have been unsatisfactory.We performed a meso-intrahepatic portal vein bypass(MIPVB),an innovative alternative to the MRB,for this patient with extensive post-operative adhesions,perihilar collaterals,and cavernous transformation.MIPVB creation in patients where the Rex recess is inaccessible is technically challenging.But with a multidisciplinary team approach,meticulous preoperative planning,and close follow-up,the authors have demonstrated that it is a safe and feasible option for patients with late-onset EHPVO after liver transplantation.

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.

James Hogarth Pringle and his time-honored maneuver

The classical method to control blood loss during parenchymal transection of the liver is the Pringle maneuver.In his landmark article in the Annals of Surgery in 1908,James Hogarth Pringle occluded the afferent vessels to the liver by compressing the hepatoduodenal ligament between his thumb and index finger(1).He applied this maneuver in eight patients who required emergency laparotomy for major hemorrhage after severe liver trauma.Although he succeeded in controlling blood loss,the eight patients he described unfortunately all died.This outcome did not prevent the Annals of Surgery from publishing his report after which James Hogarth Pringle was ready to enter the‘Hall of Fame’.Vascular inflow occlusion,applied in a continuous or intermittent fashion,became the mainstay technique for reducing blood loss during liver transection,and has remained so in the present era of laparoscopic and robotic liver resection(2).

Molecular profiling and patient selection for the multimodal approaches for patients with resectable colorectal liver metastases

Colorectal cancer represents the third most common cancer and about 20%are diagnosed with synchronous metastatic disease.From a historical point of view,surgery remains the mainstream treatment for resectable colorectal liver metastases(CRLM).Furthermore,disease outcomes are improving due significant advances in systemic treatments and diagnostic methods.However,the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question.Thus,patient selection combining image workouts,time of recurrence,positive lymph nodes,and molecular biomarkers can improve the decision-making process.Nevertheless,molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment.Tumor biomakers,genetic profiling,and circulating tumor DNA have been used to offer as much personalized treatment as possible,based on the precision oncology concept of tailored care rather than a guideline-based therapy.This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

Understanding evidence-based clinical practice guidelines for cholelithiasis 2021

Cholelithiasis is characterized by impaired metabolism of bile acids,cholesterol and bilirubin resulting in deposition of gallstones within the gallbladder(1).The article by Fujita et al.outlines the third revision of the evidence-based practice guidelines issued by the Japanese Society of Gastroenterology(JSGE)on cholelithiasis(2).For these current guidelines,52 questions were adopted through discussions among committee members,covering epidemiology,pathogenesis,diagnosis,treatments,complications,and prognostic aspects of cholelithiasis in Japan(2).The strengths of recommendations were determined by voting by committee members after assessing current available literature,patient preferences,and cost-benefit balance(2).Similar to the previous guideline(second revision),consensus among committee members was defined as the acquisition of 70%votes or over(2).

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy:a narrative review

Background and Objective:Immune checkpoint inhibitor(ICI)-based therapy has achieved impressive success in various cancer types.Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma(HCC)in recent decade.Meanwhile,numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival,respectively.In this review,we aim to summarize some pragmatic histomorphologic,immunohistochemical,and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC.Methods:We searched PubMed using the terms hepatocellular carcinoma,immunotherapy,immune checkpoint inhibitor,immune checkpoint blockade,conversion therapy,neoadjuvant therapy,adjuvant therapy,biomarker,pathologic evaluation,pathologic assessment till February 2023.Key Content and Findings:Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens,it is encouraging that a few of studies have concentrated on this field,and moreover,the methods and parameters noted on other cancer types are also worthy of reference.For the pathologic assessment of HCC specimens underwent immunotherapy,a suitable sampling scheme,identifying immunotherapy-related pathologic response,and quantification of pathologic response rate should be emphasized.For the patients of HCC who are scheduled to receive immunotherapy,tumor-infiltrating lymphocyte,intratumoral tertiary lymphoid structure,programmed cell death ligand 1,Wnt/β-catenin,microsatellite instability and mismatch repair,tumor mutational burden and tumor neoantigen,as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI.Conclusions:The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report.Albeit many related researches are preclinical or insufficient,they may tremendously alter the immunotherapy strategy of HCC in future.

Validation of the European Association for the Study of the Liver algorithm for the noninvasive diagnosis of advanced fibrosis in metabolic-dysfunction associated steatotic liver disease

Metabolic-dysfunction associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD)(1),is characterized by the accumulation of fat in the liver cells,independent of excessive alcohol consumption and has emerged as the most prevalent chronic liver condition in Western countries,underscoring a significant public health concern(2).The progression of MASLD to advanced fibrosis,marked by excessive extracellular matrix deposition and scar tissue formation,is a critical stage in MASLD natural history that significantly increases the risk of liver-related complications mortality(3).Non-invasive tests(NITs),such as liver stiffness measurement(LSM)with transient elastography(TE)and serum biomarkers,have gained prominence for assessing liver fibrosis in patients with suspected/confirmed NAFLD,offering a safer and less invasive alternative to liver biopsy(4).