Machine learning in liver surgery:Benefits and pitfalls

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of interest.However,we must be cautious with the results.In this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the future.Although the future faces significant challenges,it also holds a great potential.

Trend of robot-assisted surgery system in gastrointestinal and liver surgery: A bibliometric analysis

BACKGROUND Robot-assisted gastrointestinal and liver surgery has been an important development direction in the field of surgery in recent years and it is also one of the fastest developing and most concerning fields in surgical operations.AIM To illustrate the major areas of research and forward-looking directions over the past twenty-six years.METHODS Using the Web of Science Core Collection database,a comprehensive review of scholarly articles pertaining to robot-assisted gastrointestinal and liver surgery was researched out between 2000 and 2023.We used Citespace(Version 6.2.4)and Bibliometrix package(Version 4.3.0)to visualize the analysis of all publications including country,institutional affiliations,authors,and keywords.RESULTS In total,346 articles were retrieved.Surgical Endoscopy had with the largest number of publications and was cited in this field.The United States was a core research country in this field.Yonsei University was the most productive institution.The current focus of this field is on rectal surgery,long-term prognosis,perioperative management,previous surgical experience,and the learning curve.CONCLUSION The scientific interest in robot-assisted gastrointestinal and liver surgery has experienced a significant rise since 1997.This study provides new perspectives and ideas for future research in this field.

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors(pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.

Navigated liver surgery:State of the art and future perspectives

Background:In recent years,the development of digital imaging technology has had a significant influence in liver surgery.The ability to obtain a 3-dimensional(3D)visualization of the liver anatomy has provided surgery with virtual reality of simulation 3D computer models,3D printing models and more recently holograms and augmented reality(when virtual reality knowledge is superimposed onto reality).In addition,the utilization of real-time fluorescent imaging techniques based on indocyanine green(ICG)uptake allows clinicians to precisely delineate the liver anatomy and/or tumors within the parenchyma,applying the knowledge obtained preoperatively through digital imaging.The combination of both has transformed the abstract thinking until now based on 2D imaging into a 3D preoperative conception(virtual reality),enhanced with real-time visualization of the fluorescent liver structures,effectively facilitating intraoperative navigated liver surgery(augmented reality).Data sources:A literature search was performed from inception until January 2021 in MEDLINE(Pub Med),Embase,Cochrane library and database for systematic reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases.Results:Fifty-one pertinent articles were retrieved and included.The different types of digital imaging technologies and the real-time navigated liver surgery were estimated and compared.Conclusions:ICG fluorescent imaging techniques can contribute essentially to the real-time definition of liver segments;as a result,precise hepatic resection can be guided by the presence of fluorescence.Furthermore,3D models can help essentially to further advancing of precision in hepatic surgery by permitting estimation of liver volume and functional liver remnant,delineation of resection lines along the liver segments and evaluation of tumor margins.In liver transplantation and especially in living donor liver transplantation(LDLT),3D printed models of the donor’s liver and models of the recipient’s hilar anatomy can contribute further to improving the results.In particular,pediatric LDLT abdominal cavity models can help to manage the largest challenge of this procedure,namely large-for-size syndrome.

Three-dimensional modeling in complex liver surgery and liver transplantation

Liver resection and transplantation are the most effective therapies for many hepatobiliary tumors and diseases.However,these surgical procedures are challenging due to the anatomic complexity and many anatomical variations of the vascular and biliary structures.Three-dimensional(3D)printing models can clearly locate and describe blood vessels,bile ducts and tumors,calculate both liver and residual liver volumes,and finally predict the functional status of the liver after resection surgery.The 3D printing models may be particularly helpful in the preoperative evaluation and surgical planning of especially complex liver resection and transplantation,allowing to possibly increase resectability rates and reduce postoperative complications.With the continuous developments of imaging techniques,such models are expected to become widely applied in clinical practice.

Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges?

The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome(MS) and its associated liver manifestation, non-alcoholic fatty liver disease(NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words "metabolic syndrome", "liver resection", "liver transplantation", "non alcoholic fatty liver disease", "non-alcoholic steatohepatitis" and "liver cancer". On one hand, the MS favors the development of primary liver malignancies(hepatocellular carcinoma and cholangiocarcinoma)either through NAFLD liver parenchymal alterations(steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management.

Current status of minimally invasive liver surgery for cancers

Hepatocellular carcinoma(HCC)patients have chronic liver disease with functional deterioration and multicentric oncogenicity.Liver surgeries for the patients should be planned on both oncological effects and sparing liver function.In colorectal patients with post-chemotherapy liver injury and multiple bilateral tumors,handling multiple tumors in a fragile/easy-to-bleed liver is an important issue.Liver surgery for biliary tract cancers is often performed as a resection of large-volume functioning liver with extensive lymphadenectomy and bile duct resection/reconstruction.Minimally invasive liver surgery(MILS)for HCC is applied with the advantages of laparoscopic for cases of cirrhosis or repeat resections.Small anatomical resections using the Glissonian,indocyanine greenguided,and hepatic vein-guided approaches are under discussion.In many cases of colorectal liver metastases,MILS is applied combined with chemotherapy owing to its advantage of better hemostasis.Two-stage hepatectomy and indocyanine green-guided tumor identification for multiple bilateral tumors are under discussion.In the case of biliary tract cancers,MILS with extensive lymphadenectomy and bile duct resection/reconstruction are developing.A robotassisted procedure for dissection of major vessels and handling fragile livers may have advantages,and well-simulated robot-assisted procedure may decrease the difficulty for biliary tract cancers.

Safety and efficacy of acute normovolemic hemodilution during liver surgery: a Meta-analysis

Objective The aim of this study was to evaluate the safety and efficacy of acute normovolemic hemodilution(ANH) during liver surgery.Methods Structured searches of the Pub Med,Chinese Biological Medicine Database,and Cochrane Library electronic databases were performed,followed by a meta-analysis of outcomes,including intraoperative blood transfusion(s),intraoperative bleeding,postoperative hematocrit(Hct) levels,postoperative prothrombin time(PT),and number of patients who underwent transfusions during liver surgery.Results In total,14 eligible studies were included in the meta-analysis,which revealed that ANH for liver resection was associated with a reduction in intraoperative blood transfusions [weighted mean difference(WMD)-1.99;95% confidence interval(CI)-2.82 to -1.16;P<0.00001].The ANH group experienced less intraoperative bleeding(WMD -72.81;95% CI -136.12 to -9.50;P<0.00001) and exhibited a lower postoperative Hct level(WMD -3.38;95% CI -7.14 to -0.67;P<0.00001) than the control group.Moreover,meta-analysis revealed that postoperative prothrombin time was not affected by ANH(WMD -0.02;95% CI -0.18 to -0.32;P=0.65).Finally,the number of patients requiring allogeneic transfusion was significantly smaller in the ANH group than in the control group(odds ratio 0.13;95% CI 0.09 to 0.18;P=0.24).Conclusion Results of the present meta-analysis indicated that ANH can reduce intraoperative bleeding and the need for blood transfusions.In addition,ANH did not negatively affect the coagulation system after surgery;therefore,ANH appears to be safe and effective during liver surgery.

Clinical use of augmented reality,mixed reality,three-dimensionalnavigation and artificial intelligence in liver surgery

A precise knowledge of intra-parenchymal vascular and biliary architecture and the location of lesions in relation to the complex anatomy is indispensable to perform liver surgery.Therefore,virtual three-dimensional(3D)-reconstruction models from computed tomography/magnetic resonance imaging scans of the liver might be helpful for visualization.Augmented reality,mixed reality and 3Dnavigation could transfer such 3D-image data directly into the operation theater to support the surgeon.This review examines the literature about the clinical and intraoperative use of these image guidance techniques in liver surgery and provides the reader with the opportunity to learn about these techniques.Augmented reality and mixed reality have been shown to be feasible for the use in open and minimally invasive liver surgery.3D-navigation facilitated targeting of intraparenchymal lesions.The existing data is limited to small cohorts and description about technical details e.g.,accordance between the virtual 3D-model and the real liver anatomy.Randomized controlled trials regarding clinical data or oncological outcome are not available.Up to now there is no intraoperative application of artificial intelligence in liver surgery.The usability of all these sophisticated image guidance tools has still not reached the grade of immersion which would be necessary for a widespread use in the daily surgical routine.Although there are many challenges,augmented reality,mixed reality,3Dnavigation and artificial intelligence are emerging fields in hepato-biliary surgery.

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.

Does enhanced recovery after surgery programs improve clinical outcomes in liver cancer surgery?

Enhanced recovery after surgery(ERAS)programs have been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016 and the new recommendations in 2022.Liver surgery is usually performed in oncological patients(liver metastasis,hepatocellular carcinoma,cholangiocarcinoma,etc.),but the real impact of liver surgery ERAS programs in oncological outcomes is not clearly defined.Theoretical advantages of ERAS programs are:ERAS decreases postoperative complication rates and has been demonstrated a clear relationship between complications and oncological outcomes;a better and faster posto-perative recovery should let oncologic teams begin chemotherapeutic regimens on time;prehabilitation and nutrition actions before surgery should also improve the performance status of the patients receiving chemotherapy.So,ERAS could be another way to improve our oncological results.We will discuss the literature about liver surgery ERAS focusing on its oncological implications and future investigations projects.

Alcohol associated liver disease and bariatric surgery:Current perspectives and future directions

Bariatric surgery is a routinely performed procedure and is associated with a reduction in all-cause mortality in patients with obesity.However,bariatric sur-gery has also been linked to increased alcohol use with up to 30%of these patients developing alcohol use disorder(AUD).The mechanism of AUD after bariatric surgery is multifactorial and includes anatomic,metabolic,and neurohumoral changes associated with post-surgical anatomy.These patients are at increased risk of alcohol associated liver disease and,in some cases,require liver trans-plantation.In this article,we provide a scoping review of epidemiology,patho-physiology,and clinical outcomes of alcohol-related health conditions after bariatric surgery.

A narrative review of the current and future role of robotic surgery in liver surgery and transplantation

Background:Minimally invasive surgery(MIS)is the technique of choice in selected patients for the treatment of liver tumors.The robotic approach is considered today the natural evolution of MIS.The application of the robotic technique in liver transplantation(LT)has been recently evaluated,especially in the living donation.The aim of this paper is to review the current role of the MIS and robotic donor hepatectomy in the literature and to evaluate the possible future implication in the transplant field.Methods:We conducted a narrative review using PubMed and Google Scholar for reports published so far,using the following keywords:minimally invasive liver surgery,laparoscopic liver surgery,robotic liver surgery,robotic living donation,laparoscopic donor hepatectomy and robotic donor hepatectomy.Results:Several advantages have been claimed in favor of robotic surgery:three-dimensional(3-D)imaging with stable and high-definition view;a more rapid learning curve than the laparoscopic one;the lack of hand tremors and the freedom of movements.Compared to open surgery,the benefits showed in the studies evaluating the robotic approach in the living donation are:less postoperative pain,the shorter period before returning to normal activity despite sustaining longer operation time.Furthermore,the 3-D and magnification view makes the technique excellent in distinguishing the right plane of transection,vascular and biliary anatomy,associated with high precision of the movements and a better bleeding control(essential for donor safety)and lower rate of vascular injury.Conclusions:The current literature does not fully support the superiority of the robotic approach versus laparoscopic or open method in living donor hepatectomy.Robotic donor hepatectomy performed by teams with high expertise and in properly selected living donors is safe and feasible.However,further data are necessary to evaluate properly the role of robotic surgery in the field of living donation.

Recent advances in computerized imaging and its vital roles in liverdisease diagnosis, preoperative planning, and interventional liversurgery: A review

The earliest and most accurate detection of the pathological manifestations of hepatic diseases ensures effective treatments and thus positive prognostic outcomes.In clinical settings,screening and determining the extent of a pathology are prominent factors in preparing remedial agents and administering approp-riate therapeutic procedures.Moreover,in a patient undergoing liver resection,a realistic preoperative simulation of the subject-specific anatomy and physiology also plays a vital part in conducting initial assessments,making surgical decisions during the procedure,and anticipating postoperative results.Conventionally,various medical imaging modalities,e.g.,computed tomography,magnetic resonance imaging,and positron emission tomography,have been employed to assist in these tasks.In fact,several standardized procedures,such as lesion detection and liver segmentation,are also incorporated into prominent commercial software packages.Thus far,most integrated software as a medical device typically involves tedious interactions from the physician,such as manual delineation and empirical adjustments,as per a given patient.With the rapid progress in digital health approaches,especially medical image analysis,a wide range of computer algorithms have been proposed to facilitate those procedures.They include pattern recognition of a liver,its periphery,and lesion,as well as pre-and postoperative simulations.Prior to clinical adoption,however,software must conform to regulatory requirements set by the governing agency,for instance,valid clinical association and analytical and clinical validation.Therefore,this paper provides a detailed account and discussion of the state-of-the-art methods for liver image analyses,visualization,and simulation in the literature.Emphasis is placed upon their concepts,algorithmic classifications,merits,limitations,clinical considerations,and future research trends.

Non-anatomical liver resection for hepatocellular carcinoma:the SegSubTe classification to overcome the problem of heterogeneity

Background:The superiority of anatomical resection(AR)vs.non-anatomical resection(NAR)in the surgical management of hepatocellular carcinoma(HCC)is debated.ARs are well-defined procedures,whereas the lack of NAR standardization results in heterogeneous outcomes.This study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the tumor.Methods:A single-center retrospective analysis of pre-and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was conducted.The quality of surgery was assessed classifying the type of vascular supply and the level of surgical section(segmental,subsegmental or terminal next to the tumor)of vascular pedicles feeding the HCCs;then,the population was divided in“SegSubTe-IN”or“SegSubTe-OUT”groups,and the tumor recurrence and survival were analyzed.Results:Ninety-seven patients who underwent NAR were included;76%were SegSubTe-IN and 24%were SegSubTe-OUT.Total disease recurrence,local recurrence and cut-edge recurrence in the SegSubTe-IN vs.SegSubTe-OUT groups were 50%vs.83%(P=0.006),20%vs.52%(P=0.003)and 16%vs.39%(P=0.020),respectively.SegSubTe-OUT odds ratio for local recurrence was 4.1 at univariate regression analysis.One-,three-,and five-year disease-free survival rates in the SegSubTe-IN vs.SegSubTe-OUT groups were 81%,58%and 35%vs.46%,21%and 11%,respectively(P<0.001).Conclusions:The SegSubTe classification is a useful tool to stratify and standardize NAR for HCC,aiming at improving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC.

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.

Rethinking the Barcelona clinic liver cancer guidelines:Intermediate stage and Child-Pugh B patients are suitable for surgery?

According to Barcelona Clinic Liver Cancer recommendations,intermediate stage hepatocellular carcinomas(stage B)are excluded from liver resection and are referred to palliative treatment.Moreover,Child-Pugh B patients are not usually candidates for liver resection.However,many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection,maintaining that hepatic resection is not contraindicated in selected patients with non–early-stage hepatocellular carcinoma and without normal liver function.Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification,and this treatment gives good results in the setting of multinodular,large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis.In this review we explore this controversial topic,and we show through the literature analysis how liver resection may improve the short-and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients.However,other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.

Prospective study to evaluate the prognostic value of different nutritional assessment scores in liver surgery: NURIMAS Liver (DRKS00006340)

Background:Malnutrition is recognised as a preoperative risk factor for patients undergoing hepatic resection.It is important to identify malnourished patients and take preventive therapeutic action before surgery.However,there is no evidence regarding which existing nutritional assessment score(NAS)is best suited to predict outcomes of liver surgery.Methods:All patients scheduled for elective liver resection at the surgical department of the University Hospital of Heidelberg and the Municipal Hospital of Karlsruhe were screened for eligibility.Twelve NASs were calculated before operation,and patients were categorised according to each score as being either at risk or not at risk for malnutrition.The association of malnutrition according to each score and occurrence of at least one major complication was the primary endpoint,which was achieved using a multivariate logistic regression analysis including established risk factors in liver surgery as covariates.Results:The population consisted of 182 patients.The percentage of patients deemed malnourished by the NAS varied among the different scores,with the lowest being 2.20%(Mini Nutritional Assessment)and the highest 52.20%(Nutritional Risk Classification).Forty patients(22.0%)had a major complication.None of the scores were significantly associated with major complications.Conclusions:None of the twelve investigated NAS defined a state of malnutrition that was independently associated with postoperative complications.Other means of measuring malnutrition in liver surgery should be investigated prospectively.

Repeat liver surgery by laparoscopy for a malignant recurrence after previous open or laparoscopic resection

Aim:This paper reported the experience of one center on repeat laparoscopic liver surgery for metastasis and hepatocellular carcinoma(HCC)with a review of the literature.Methods:This retrospective study included 24 patients who underwent laparoscopic re-intervention(hepatic resection and radiofrequency ablation)for recurrent HCC in cirrhosis(n=17)and for recurrent malignant metastases(n=7)after a previous open or laparoscopic procedure.Patients were divided into two groups according to the fi rst surgical approach.Group 1 underwent open resection and laparoscopic procedure(7 patients),and Group 2 underwent laparoscopic resection and laparoscopic procedure(17 patients).Results:Mean operative time for re-intervention was signifi cantly longer for Group 1(220.14±80.06 min)than for Group 2(150±56.18 min;P=0.001),whereas the mean blood loss and mean hospital stay were comparable in both groups.According to Dindo-Clavien classifi cation,overall morbidity ranged between Grade I and IIIa and was similar in both groups.Conclusion:This study suggests that repeat laparoscopic surgery for recurrent hepatic malignant diseases in selected patients is a feasible and safe procedure with good short-term outcomes,but further prospective studies are needed to support these results.

Protective benefit of minimally invasive liver surgery for hepatocellular carcinoma prior to transplant

Aim:The purpose of this study is to assess the benefit of laparoscopic liver resection(LLR)for hepatocellular carcinoma(HCC)given recurrence and future need for liver transplantation(LT).Methods:Data on liver resections were gathered from the Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione(IRCCS-ISMETT)from 2003-2021.A retrospective analysis of 1408 consecutive adult patients who had a liver resection was performed with categorization based on the underlying disease process.A sub-analysis studied the 291 patients who had an LLR with an intention to transplant approach after LLR.Results:From 2012 to 2020,ISMETT’s mean annual LLR rate was 45%.Data suggests that a laparoscopic approach to iterative surgical treatment for HCC has demonstrated protective benefits.Compared to open surgery or LT,LLR is protective against the risk of de-listing,post-transplant patient death,tumor recurrence,adhesions,and bleeding in a cirrhotic patient.Kaplan Meier’s analysis showed no difference between post-LT survival curves for those with prior open abdominal surgery or LLR(P=0.658).Conclusion:Laparoscopic surgery has important protective advantages over laparotomy surgery for the surgical treatment of HCC,particularly since treatment is not always curative.LLR can be considered a bridge therapy for transplantation,ensuring less crowding of waiting lists,a desirable condition in areas of donor storage.