Risk Of Postoperative Liver Failure Research Articles

The Effect of Diabetes Mellitus Type 1 on the Energy Metabolism of Hepatocytes: Multiphoton Microscopy and Fluorescence Lifetime Imaging

A decrease in the regenerative potential of the liver during the development of non-alcoholic fatty liver disease (NAFLD), which is observed in the vast majority of patients with diabetes mellitus type 1, significantly increases the risk of postoperative liver failure. In this regard, it is necessary to develop new approaches for the rapid intraoperative assessment of the condition of liver tissue in the presence of concomitant liver pathology. A modern label-free approach based on multiphoton microscopy, second harmonic generation (SHG), and fluorescence lifetime imaging microscopy (FLIM) allow for the evaluation of the structure of liver tissue as well as the assessment of the metabolic state of hepatocytes, even at the cellular level. We obtained optical criteria and identified specific changes in the metabolic state of hepatocytes for a reduced liver regenerative potential in the presence of induced diabetes mellitus type 1. The obtained criteria will expand the possibilities for the express assessment of the structural and functional state of liver tissue in clinical practice.

Volumetric Remodeling of the Left Liver After Right Hepatectomy: Analysis of Factors Predicting Degree of Hypertrophy and Post-hepatectomy Liver Failure

BackgroundThis study investigated the volumetric remodeling of the left liver after right hepatectomy looking for factors predicting the degree of hypertrophy and severe post-hepatectomy liver failure (PHLF). MethodsIn a cohort of 121 right hepatectomies, we performed CT volumetrics study of the future left liver remnant (FLR) preoperatively and postoperatively. Factors influencing FLR degree of hypertrophy and severe PHLF were identified by multivariate analysis. ResultsAfter right hepatectomy, the mean degree of hypertrophy and kinetic growth rate of the left liver remnant were 25% and 3%/day respectively. The mean liver volume recovery rate was 77%. Liver remodeling volume was distributed for 79% on segments 2 and 3 and 21% on the segment 4 (p<0.001). Women showed a greater hypertrophy of segments 2 and 3 compared with men (p=0.002). The degree of hypertrophy of segment 4 was lower in case of middle hepatic vein resection (p=0.004). Left liver remnant kinetic growth rate was associated with the standardized future liver remnant (sFLR) (p<0.001) and a two-stage hepatectomy (p=0.023). Severe PHLF were predicted by intraoperative transfusion (p=0.009), biliary tumors (p=0.013), and male gender (p=0.022). ConclusionsVolumetric remodeling of the left liver after right hepatectomy is not uniform and is mainly influenced by gender and sacrifice of middle hepatic vein. Male gender, intraoperative transfusion, and biliary tumors increase the risk of postoperative liver failure after right hepatectomy.

Extended Right Hepatectomy to Inferior Vena Cava Under Total Vascular Exclusion, Veno-Venous Bypass and In Situ Hypothermic Perfusion of the Future Liver Remnant.

Venous obstruction at the hepatic veins-inferior vena cava confluence can be particularly challenging to manage if an associated liver resection is needed. Total vascular exclusion (TVE) with veno-venous bypass (VVB) and hypothermic in situ perfusion (HP) of the future liver remnant can be used in these conditions.1,2 METHODS: The patient was a 58-year-old with a voluminous adrenal cancer invading the kidney, the right liver and the retrohepatic inferior vena cava with intraluminal thrombus extending up to the hepatic veins confluence. A right hepatectomy, extended to segment 1, the right kidney, and the retrohepatic inferior vena cava was planned. The parenchymal liver transection was performed under a TVE, VVB, and HP of the left liver to decrease blood losses and risk of postoperative liver failure. Vena cava reconstruction was achieved by a ringed Gore-Tex prosthesis with reimplantation of the left renal vein. Total duration of veno-venous bypass and liver vascular exclusion were 2 h 40 min and 2 h 10 min, respectively. The patient was discharged on postoperative day 17. Total vascular exclusion with veno-venous bypass and in-situ liver hypothermic perfusion increases the safety of major liver resection requiring complex vascular reconstruction.1,2 TVE under VVB and HP of the future liver remnant is used at our institution when: (1) TVE will last more than 30 min; (2) vascular reconstruction is needed; (3) in the presence of venous obstruction; (4) in the presence of injured liver parenchyma; and (5) in the presence of cardiovascular comorbidities.

Prognostic biomarkers in and selection of surgical patients with hepatocellular carcinoma.

The Faculty of Health and Medical Sciences at the University of Copenhagen has accepted this dissertation for public defence for the doctoral degree in medicine, Copenhagen, January 10, 2023 Bente Merete Stallknecht, Head of Faculty Assessment committee Chair Professor Susanne Dam Poulsen, University of Copenhagen Opponents Professor Pål-Dag Line, University of Oslo Professor Christian Toso, University of Geneva Chair of the defence ceremony Professor Kirsten Grønbæk, University of Copenhagen The defense took place on February 14, 2023 at 14:00 CET at Rigshospitalet, Auditorium 2, Blegdamsvej 9, 2100 Copenhagen Ø This thesis summarizes a significant part of the research that I carried out from 2015 to 2020 alongside my surgical specialization. Since defending my PhD in 2013, my research area of interest has shifted towards liver surgery and transplantation, in particular prognostic aspects related to malignancy. The complexity of liver surgery, including anatomy, technique and medical aspects has always sparked my interest. The work in this thesis has paved the way for the current and future area of interest of my research group at Department of Surgery and Transplantation, Rigshospitalet. I would like to express my deepest appreciation to Allan Rasmussen for inspiration and guidance. Allan introduced me to this specific field of research and to many important research partners in Rigshospitalet, Denmark and Scandinavia. I would like to thank Jens Hillingsø and all of my wonderful colleagues at Department of Surgery and Transplantation, Rigshospitalet for their support and for offering me the opportunity to carry out my research. I would also like to thank the collaborators on the studies for their excellent work and important scientific inputs. These include: Andreas Rostved, Carina Lund Sørensen, Peter Nørgaard Larsen and Nicolai Schultz, Department of Surgery and Transplantation, Rigshospitalet; Jakob Burcharth and Jacob Rosenberg, Department of Surgery, Herlev Hospital; Jane Preuss Hasselby and Gro Linno Willemoe, Department of Pathology, Rigshospitalet; Jan-Michael Kugler, Institute for Molecular and Cellular Medicine, Panum Institute; Christina Westmose Yde, Lise Ahlborn and Finn Cillius Nielsen, Center for Genomic Medicine, Rigshospitalet; Claus Lindbjerg Andersen and Tenna Henriksen, Department for Molecular Medicine (MOMA), Aarhus University Hospital/Skejby; Kristoffer Rohrberg, Phase 1 Unit, Department of Oncology, Rigshospitalet; Lau Caspar Thygesen, National Institute of Public Health, University of Southern Denmark; and the European Liver and Intestine Transplant Association (ELITA) study group. Thanks to my research group for daily inspiration, good discussions and laughs (Delal Akdag, Jeanett Klubien, Lucas Knøfler og Sophie Nordkild). This work was financially supported by the Harboe foundation, the Risom foundation and the Dagmar Marchall foundation, for which I am grateful. Finally, I would like to thank my wife Line for her tremendous support over the many years where my research mostly has been conducted in my spare time. Thanks to my three children for filling me with love each day and thanks to my mother and my brother for continuous support. A special thanks to my father who passed away in the fall. He was always proud, supportive and encouraging. Hans-Christian PommergaardMD, DMSc, PhDDepartment of Surgery and TransplantationRigshospitalet, University of Copenhagen Charlottenlund, January 2023 Pommergaard HC, Burcharth J, Rosenberg J, Rasmussen A. Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation: a systematic review and meta-analysis. Transplant Rev (Orlando). 2016 Jul;30(3):171–7. Pommergaard HC, Hasselby JP, Willemoe GL, Ralbovska A, Rostved AA, Rasmussen A, Schultz NA, Hillingsø J, Larsen PN, Kugler JM. Peroxisome proliferator-activated receptor activity correlates with poor survival in patients resected for hepatocellular carcinoma. J Hepatobiliary Pancreat Sci. 2021 Apr;28(4):327–35. Pommergaard HC, Rasmussen A, Hillingsø J, Kugler JM. Aldehyde dehydrogenase expression may be a prognostic biomarker and associated with liver cirrhosis in patients resected for hepatocellular carcinoma. Surg Oncol. 2021 Nov 23;40:101677. Pommergaard HC, Yde CW, Ahlborn LB, Andersen CL, Henriksen TV, Hasselby JP, Rostved AA, Sørensen CL, Rohrberg KS, Nielsen FC, Rasmussen A. Personalized circulating tumour DNA in patients with hepatocellular carcinoma: a pilot study. Mol Biol Rep. 2021 Nov 22. Pommergaard HC, Rostved AA, Adam R, Thygesen LC, Salizzoni M, Gómez Bravo MA, Cherqui D, Filipponi F, Boudjema K, Mazzaferro V, Soubrane O, García-Valdecasas JC, Prous JF, Pinna AD, O'Grady J, Karam V, Duvoux C, Rasmussen A. Vascular invasion and survival after liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry. HPB (Oxford). 2018 Aug;20(8):768–75. Pommergaard HC, Rostved AA, Adam R, Thygesen LC, Salizzoni M, Gómez Bravo MA, Cherqui D, De Simone P, Boudjema K, Mazzaferro V, Soubrane O, García-Valdecasas JC, Fabregat Prous J, Pinna AD, O'Grady J, Karam V, Duvoux C, Rasmussen A. Locoregional treatments before liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry. Transpl Int. 2018 May;31(5):531–9. Pommergaard HC, Rostved AA, Adam R, Rasmussen A, Salizzoni M, Gómez Bravo MA, Cherqui D, De Simone P, Houssel-Debry P, Mazzaferro V, Soubrane O, García-Valdecasas JC, Prous JF, Pinna AD, O'Grady J, Karam V, Duvoux C, Thygesen LC. Mortality after transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry. Liver Cancer. 2020 Aug;9(4):455–67. Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of cancer deaths globally with increasing incidence. In most cases, HCC develops as a result of an underlying chronic liver disease. The stage at the time of diagnosis is closely correlated with prognosis with a 5-year survival of more than 70% for patients with early-stage HCC. These patients are generally suitable for curative treatment, such as resection, ablation or liver transplantation. In contrast, 5-year survival may be as low as 5% for patients in advanced stages of the disease. Due to organ shortage and the risk of mortality for patients on the waiting list for liver transplantation, survival in patients undergoing transplantation due to HCC should be comparable to those with benign indications. However, there is an ongoing debate concerning the best criteria for the selection of patients with HCC for transplantation, as the current criteria may rule out patients with a good prognosis. Liver resection may be performed in patients with HCC in non-cirrhotic livers and cirrhotic livers with preserved liver function. However, careful selection of patients is crucial due to high recurrence risk (>50%) and severe complications in >10% of liver resections for HCC. The aims of this thesis were to identify prognostic biomarkers in and improve the selection of patients undergoing transplantation and resection for HCC, respectively. Yet another aim was to improve upon the existing early detection of recurrence. The seven studies included in this thesis provided novel insights into prognostic biomarkers and selection of surgical patients with HCC. Firstly, the literature was reviewed regarding biomarkers to detect recurrence after transplantation for HCC. Next, two novel tumour-related prognostic biomarkers were identified and the applicability of circulating tumour DNA (ctDNA) was evaluated. Moreover, using data from the European Liver Transplant Registry (ELTR), vascular invasion and locoregional treatment were identified as important prognostic markers. Lastly, using propensity score calibration, prognostic differences between HCC in cirrhotic and non-cirrhotic livers were clarified. The studies included in this thesis add important knowledge towards better selection of patients for transplantation and resection of HCC, respectively. In future guidelines, alpha-fetoprotein, radiological markers of vascular invasion and response to locoregional treatment may be included in selection criteria for transplantation of patients with HCC. In addition, the novel biomarkers identified may add important prognostic information and improve the selection of patients. For resected patients, a proper balance between survival benefit and risk of recurrence and complications may be ensured. For transplanted patients, optimized selection means that the utility of donor organs is maximized by more accurately selecting patients with favourable tumour biologies. Hepatocellulært karcinom (HCC) er den sjette mest almindelige kræftsygdom og den fjerde hyppigste årsag til kræftdødsfald globalt med stigende forekomst. I de fleste tilfælde udvikler HCC sig som følge af en underliggende kronisk leversygdom. Stadie på diagnosetidspunktet er tæt korreleret med prognose med femårs overlevelse på mere end 70% hos patienter med HCC i tidligt stadium. Disse patienter kan generelt modtage kurativt intenderet behandling, såsom resektion, ablation eller levertransplantation. I modsætning hertil kan femårs overlevelse være helt ned til 5% hos patienter med fremskredne stadier. På grund af organmangel og død på venteliste til levertransplantation bør overlevelse hos patienter der transplanteres for HCC være sammenlignelig med overlevelse for benigne indikationer. Der er aktuelt debat om de bedste kriterier til at selektere patienter med HCC til transplantation, da nuværende kriterier udelukker visse patienter med en god prognose. Leverresektion kan udføres hos patienter med HCC i en ikke-cirrotisk lever eller i en cirrotisk lever med bevaret leverfunktion. Imidlertid er omhyggelig udvælgelse af patienter afgørende på grund af en høj risiko for recidiv (>50%) og alvorlige komplikationer i >10% af leverresektioner for HCC. Formålet med denne disputats var at identificere prognostiske biomarkører og forbedre selektion af patienter til henholdsvis transplantation og resektion for HCC. Desuden var målet at forbedre tidlig identifikation af recidiv. De syv studier inkluderet i denne disputats giver ny indsigt i prognostiske biomarkører og selektion af kirurgiske patienter med HCC. Eksisterende biomarkører for recidiv efter transplantation for HCC blev systematisk undersøgt. Dernæst blev to nye tumorrelaterede prognostiske biomarkører identificeret, og anvendeligheden af cirkulerende tumor-DNA (ctDNA) blev evalueret. Ved hjælp af data fra European Liver Transplant Registry (ELTR) blev mikrovaskulær invasion og lokalbehandling af HCC identificeret som vigtige prognostiske markører. Endelig blev prognostiske forskelle mellem HCC i cirrotisk og ikke-cirrotisk lever afklaret ved hjælp af propensity score kalibrering. Studierne inkluderet i denne disputats tilfører vigtig viden til bedre selektion af patienter til henholdsvis transplantation og resektion af HCC. I fremtidige retningslinjer kan alfa-føto protein, radiologiske markører for microvaskulær invasion og respons på lokalbehandling muligvis inkluderes i selektionskriterier for transplantation af HCC. Derudover kan de nye identificerede biomarkører tilføje vigtig prognostisk information og forbedre udvælgelsen af patienter. For resecerede patienter kan der skabes en balance mellem overlevelsesgevinst og risiko for recidiv og komplikationer. For transplanterede patienter betyder optimeret selektion, at udnyttelse af donororganer maksimeres ved mere præcis udvælgelse patienter med en gunstig tumorbiologi. Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of cancer deaths globally with increasing incidence. HCC represents 75–85% of primary liver cancers and has a strong male predominance, both regarding incidence and mortality [1, 2]. In 70–90% of cases, HCC arises in patients with cirrhotic livers [3, 4]. Approximately one-third of patients with cirrhosis will develop HCC in their lifetime (1–8% annual incidence) [5, 6]. On a global level, hepatitis B virus (HBV) is the primary cause of HCC (33%), followed by alcohol (30%), hepatitis C virus (HCV) (21%) and other aetiologies (16%) [2]. Most deaths due to HCC occur in Asia, and the primary cause is endemic HBV infections. However, the incidence of HCC is rising in Western countries as a result of the increasing prevalence of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and alcohol-related liver disease [7]. HCC seems to be less frequent in patients with alcoholic and NASH cirrhosis than in patients with viral hepatitis [6, 8]. However, the annual incidence of HCC in patients with NASH is 1–2%, and it is estimated that 6 million people in the United States alone have NASH [9] and that obesity and/or diabetes accounts for approximately 37% of the HCC cases [10]. Current guidelines suggest that patients with cirrhosis (Child-Pugh A/B and Child-Pugh C (awaiting transplantation)) and non-cirrhotic HBV patients with intermediate or high risk of HCC should undergo surveillance for HCC with abdominal ultrasound every 6 months [11]. This modality has a limited sensitivity (45%) for the detection of HCC [12], which may be reduced further by obesity and cirrhosis [13]. However, evidence suggests that surveillance improves the identification of HCC at an early stage and hence the chances of curative treatment and survival [14]. Patients with early-stage HCC are generally suitable for curative treatments, such as resection, ablation or liver transplantation. In contrast, patients with advanced-stage disease are typically only offered palliative oncologic treatment or the best supportive care. Patients with intermediate-stage disease may be offered chemo-embolization [15]. Consequently, the stage at the time of diagnosis is closely correlated with the prognosis with a 5-year survival of more than 70% for patients with early-stage HCC compared with only 5% for patients in advanced stages of the disease [11, 16]. In most centres, a multidisciplinary approach is adopted with treatment allocation based on the stage of the disease, using, for example, the Barcelona Clinic Liver Cancer (BCLC) classification [17]. A contemporary approach includes treatment stage migration, wherein a patient with a specific disease stage not suited for the first-line treatment may be allocated a treatment recommended for a different disease stage [18-20]. The concepts are integrated with the 2022 BCLC guideline update [15] (Fig. 1). With evidence suggesting that prognosis is related to first-line treatment irrespective of tumour stage, an alternative approach has been suggested [21]. In the concept of therapeutic hierarchy (Fig. 2), treatments are decided independent of stage and hierarchical use of available therapies according to their specific survival benefit [22]. Previously, sorafenib was the only available systemic treatment. It is associated with significant adverse events and only minor survival benefits [23]. Based on the evidence from phase III trials, several additional systemic therapies have been approved including atezolizumab plus bevacizumab, lenvatinib, regorafenib, cabozantinib and ramucirumab [24]. Moreover, trials are now evaluating combination therapies. According to the 2022 guideline update from BCLC, Atezolizumab-Bevacizumab/Durvalumab-Tremelimumab is now recommended as first-line systemic treatment [15] (Fig. 1). Hepatocellular carcinoma may be diagnosed solely based on imaging using the Liver Imaging Reporting and Data System (LI-RADS) [25], thereby eliminating the need for preoperative histological diagnosis by tumour biopsy. LI-RADS is valid in patients with high-risk of developing HCC, namely patients with cirrhosis, chronic HBV and current or prior HCC. However, LI-RADS may not be applied in patients without these risk factors, in patients under 18 years of age and in those with cirrhosis due to a vascular disorder or congenital hepatic fibrosis [25]. Moreover, a recent study showed that LI-RADS may be valid in a larger proportion of patients with an increased risk of HCC than previously considered [26]. However, biopsy in patients without increased risk, including patients with non-cirrhotic livers, is still needed to confirm diagnosis. Due to organ shortage and the risk of mortality for patients on waiting list for liver transplantation, survival in patients undergoing transplantation due to HCC should be comparable to those with benign indications [27]. However, there is an ongoing debate concerning the best criteria for selection of patients with HCC for transplantation. Some argue that the current criteria may rule out patients with a good prognosis [28]. Thus, better selection criteria are needed. Patients with HCC in a non-cirrhotic liver without macrovascular invasion or extra-hepatic spread may undergo curative liver resection. Liver resection may also be performed in patients with HCC in a cirrhotic liver with preserved liver function, no portal hypertension and sufficient volume of the future liver remnant (FLR) [11]. Careful selection of patients is essential due to a high recurrence risk (>50%) [29] and severe complications in >10% of liver resections for HCC. Age, model for end-stage liver disease (MELD) score, liver stiffness and serum albumin were independent predictors of complications [30], while portal hypertension, extend of resection, MELD score, bilirubin and indocyanine green (ICG) clearance were associated with the risk of postoperative liver failure [31-33]. However, knowledge of cancer-related prognostic biomarkers is lacking. To optimize the selection of patients who will benefit from a high-risk surgical procedure, prognostic biomarkers are needed. Furthermore, as liver disease may not be easily diagnosed in some patients, additional biomarkers to identify high-risk patients, for example, with fibrosis/cirrhosis may be useful [34]. However, so far, no prognostic biomarkers have been widely accepted in clinical practice. Early identification of recurrence after surgical treatment may be associated with better prognosis [29]. Imaging studies currently used for follow-up may be insufficient for smaller lesions (<2 cm) [35, 36]. Thus, tools for early detection of recurrence are needed. Hypothesis 1 was investigated by conducting a systematic review and a meta-analysis using the PubMed and Scopus databases on studies investigating biomarkers for recurrence of HCC after liver transplantation. Hypotheses 2 and 3 were investigated using tissue stored in the Danish Cancer Biobank from patients undergoing liver resection for HCC at Rigshospitalet, Denmark between 2014 and 2018. Hypothesis 4 was investigated by evaluating the detection of ctDNA in blood preoperatively in a prospective pilot study in patients undergoing liver resection for HCC at Rigshospitalet, Denmark in 2018 and 2019. Hypotheses 5, 6 and 7 were investigated using data from the European Liver Transplant Registry (ELTR) for the period from 1990 to 2016, where pre-, peri- and postoperative data from 174 liver transplantation centres in 28 European countries have been collected, including data on tumour characteristics and locoregional treatment in patients with HCC. Regarding liver transplantation, donor livers are scarce with substantial mortality of patients in waiting lists [37]. Thus, the prognosis for recipients transplanted for HCC should be comparable to that of benign indications to justify transplantation [27]. Current selection criteria, based on the size and number of HCC, are insufficient, as they may rule out patients with good prognosis despite being outside the established criteria [28]. Inclusion of biomarkers in the selection criteria may improve the selection of patients for liver transplantation for HCC. However, except for alpha-fetoprotein (AFP), no biomarkers are included in the existing selection criteria for transplantation due to HCC. Surgical resection for HCC may be a high-risk procedure, especially in patients with cirrhosis, with a substantial risk of recurrence [11] and complications, including liver failure [30]. Prognostic biomarkers may improve the selection of patients who will benefit from a surgery and also provide more precise preoperative information to them. Currently, tumour burden, liver function and performance score are used to select patients for surgical resection [15]. Thus, biomarkers may be used in conjunction with these criteria to determine the optimal treatment strategy. Currently, no biomarkers have been widely incorporated into clinical practice. A prognostic biomarker may be defined as a factor indicating the likelihood of a future recurrence, progression or death in a population [38]. For the purpose of this thesis, a prognostic biomarker was defined as a blood or tumour marker associated with prognosis not currently included in standard diagnostic workups. A vast amount of research has been conducted in an effort to identify clinically useful biomarkers in patients with HCC. However, relatively less effort has gone into the validation of positive results. In an attempt to gain an overview of the level of evidence, directions for the design of studies and the possibilities for clinical implementation, a systematic review and a meta-analysis were conducted in Study I. PubMed and Scopus databases were searched up to the year 2016 to identify observational studies investigating blood-borne or tumour markers for recurrence of HCC after liver transplantation. Meta-analyses were performed in biomarkers investigated in multiple studies with sufficient homogeneity. Meta-analysis was omitted when heterogeneity was above 75% as assessed by the I2 test. The generic inverse variance method was utilized to incorporate adjusted hazard ratio (HR) estimates from individual studies. This was applied to adjust for confounding in individual studies. Alpha-fetoprotein was investigated in 49 studies of which 17 studies were included in the meta-analysis. These studies were defined by using a pre-transplant AFP >400 NT/mL as cut-off [39-55]. The pooled estimate (HR) regarding risk of recurrence was 2.69 [2.08–3.47], with an acceptable heterogeneity of 46% (Fig. 3). However, the funnel plot indicated a risk of publication bias with a lack of smaller negative studies. Des-gamma-carboxy prothrombin (DCP/PIVKA) was investigated in seven studies. Four studies [45, 48, 57, 58] with comparable outcome definition and cut-off levels (PIVKA level >100–400 mAU/mL) were included in a meta-analysis with an HR of 5.99 [3.27–10.98] regarding the risk of recurrence. Heterogeneity of the four studies was 0% (Fig. 4). Neutrophil to lymphocyte ratio (NLR) was found to be associated with recurrence in four studies [59-62]. However, a meta-analysis was not conducted due to the high heterogeneity (>75%) between the studies. Moreover, circulating DNA – particularly single nucleotide polymorphisms rs894151 and rs12438080 – was found to be associated with recurrence in one of the studies [63]. Following protein markers in HCC tumours has been shown to be associated with recurrence: anti-Ki67 [64], calpain small subunit 1 (Capn4) [65], CD34 antigen [66], CD147 [67], NDRG1 [68], cadherins [64], x-linked inhibitor of apoptosis protein-associated factor 1 (XAF1) [69], hepatocyte nuclear factor 1 (HNF1) [70] and hippo cell signal pathway [71]. Enzymes were investigated in four studies. Two of them investigated matrix metalloproteinases (MMPs) measured in tumour [67, 72]. In a meta-analysis, there was no association with recurrence with an HR of 2.12 [0.21–21.43], with a high heterogeneity of 74% (Fig. 5). However, MMP measured in adjacent stromal tissue may be associated with recurrence [67]. In two additional studies, histone deacetylases (HDACs) [73] and O-GlcNAcylation [52] were associated with recurrence. Micro-RNA in tumour was associated with recurrence in four studies [41, 44, 54, 74]. Moreover, long noncoding RNAs, in particular, HOTAIR in tumour [50] and MALAT-1 [75], were associated with recurrence. DNA/genes associated with recurrence included CIMP [76], MACC1 [42, 51], and cell-cycle genes pRb and p16 [77]. Lastly, allelic imbalance in microsatellites was associated with recurrence in a meta-analysis with two studies and an HR of 13.49 [3.17–57.30] and 0% heterogeneity [78, 79] (Fig. 6). The majority of biomarkers were only investigated in a single study, and results have not been validated. The included studies considered different types of aetiology for HCC, and patients may therefore not be comparable. Moreover, outcome definition differed between the studies. For meta-analyses, there was an insufficient number of studies for meaningful evaluation of publication bias by means of funnel plots, except for AFP where a lack of smaller negative studies suggested a risk of publication bias. Since the publication of Study I in 2016, additional studies have been published on biomarkers for recurrence after liver transplantation for HCC. Thus, an updated literature search was performed. Regarding blood-borne biomarkers, platelet-to-lymphocyte ratio (PLR), controlling nutritional status (CONUT) and the prognostic nutritional index (PNI) were associated with recurrence [80]. Serum homocysteine was associated with recurrence in recipients with AFP-negative disease [81]. Moreover, markers of angiogenesis and inflammation (plasma VEGFR1, VEGF and VEGF-C) and circulating exosomal miR-92b were associated with recurrence [82, 83]. Regarding tumour tissue biomarkers, increased LGALS3 and LGALS3BP gene and protein expression were associated with recurrence [84]. In addition, TP53 mutations, high fractional allelic loss, hypomethylation of 8 tumour suppressors and absence of CTNNB1 mutations were of prognostic significance [85]. Lastly, tumour evolutionary distance by genome-wide single-nucleotide polymorphism genotyping was associated with recurrence and validated in a replication cohort [86]. As in liver transplant recipients, AFP is the most commonly evaluated biomarker after liver resection for HCC. However, only 10–20% of early-stage HCC patients present with abnormal AFP, which may be correlated with an aggressive HCC type (e.g., S2 class, epithelial cell adhesion molecule (EpCAM) positive) [87-89]. Moreover, AFP has low accuracy, as elevated AFP in patients with cirrhosis may reflect viral hepatitis and background liver disease in addition to HCC development [90]. Despite these limitations, AFP level was associated with recurrence with results externally validated in international cohorts [91, 92]. Furthermore, AFP level at recurrence predicted survival [93]. The following additional blood-borne biomarkers were associated with recurrence after resection for HCC: DCP [94], albumin-bilirubin score [91], circulating EpCAM positive tumour cells [95], preoperative CRP [96], preoperative neutrophil-to-lymphocyte ratio [97] and ratio of postoperative to preoperative circulating levels of cancer stem cell (CSC) markers K19 and CD44 [98]. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear receptors that regulate lipid metabolism and transduce metabolic and nutritional signals into transcriptional responses [99-101]. The association between PPAR and the development of HCC is not fully understood, and studies are somewhat conflicting. Moreover, the relationship may depend on context and species [102]. In some studies, high PPAR activity seems beneficial. Thus, it may reduce tumour growth via anti-inflammatory mechanisms [103], improve liver function [104] and resolve NASH [105]. As opposed to this, studies suggested unwanted consequences of PPAR activation, such as the induction of HCC due to regulation of the cell cycle [106] or formation of steatosis [107]. However, the prognostic importance in patients with HCC has not been investigated in a clinical setting. In Study II, we presented the results of RNA sequencing of HCC and non-tumour liver tissue in 52 patients undergoing liver resection. Based on the expression of PPAR target genes in heat maps (Fig. 7), we identified a group of patients (cancer cluster 3) with decreased overall survival (3-year overall survival of 48.6% vs 81.7% amongst controls, Fig. 8). The correlation remained significant in multivariate analysis adjusted for age, cirrhosis, microvascular invasion, number of tumours and resection margins (Table 1). Furthermore, we found that PPAR expression in non-tumour liver tissue was correlated with cirrhosis. In an earlier study using publicly available data from The Cancer Genome Atlas (TCGA), it was found that patients with HCC and low PPAR activity in tumour had significantly reduced overall survival [109]. However, in that study, PPAR activity from tumour tissue in patients with HCC was compared with liver tissue from healthy patients. Moreover, in a large study, PPAR expression evaluated with immunohistochemistry was correlated with shorter survival [110]. While immunohistochemistry may be a good surrogate for PPAR activity, transcriptome analysis allows a more direct evaluation of activity, as PPAR requires ligands and co-receptors to regulate gene expression [111]. In a phase 2 trial, patients with NASH were randomized to receive Lanifibranor, a PPAR agonist or a placebo [112]. Patients in the treatment arm receiving 1200 mg daily had reduced disease activity measured by the steatosis, activity and fibrosis [SAF] scoring system without the worsening of fibrosis. This suggested a possible clinical implication of PPAR not confined to HCC. Together with the correlation between PPAR and cirrhosis found in Study II, these findings may reflect that PPAR activity is important for liver cell homoeostasis. To our knowledge, Study II was the first clinical study to establish the prognostic value of PPAR gene activit

Impact of Preoperative Jaundice and Biliary Drainage on Short- and Long-term Outcomes among Patients with Gallbladder Cancer

ObjectivesTo characterize the prognostic implication of jaundice and preoperative biliary drainage on postoperative outcomes among patients with gallbladder cancer (GBC) undergoing surgical resection. MethodsPatients who underwent surgical resection of GBC identified from a multicenter database between January 2000 and December 2019 were retrospectively analyzed. Data on clinical and pathological details, as well as short- and long-term overall survival (OS), were obtained and compared among patients with and without preoperative jaundice and biliary drainage. ResultsAmong 449 patients with GBC, median and 1‐, 3‐, and 5‐year OS were 17.4 months, 63.7%, 28.4%, and 22.1%, respectively. Patients who presented with preoperative jaundice (n = 100, 22.3%) were more likely to have advanced disease, a lower incidence of R0 resection (29.0% vs. 69.1%, p < 0.001), as well as a higher incidence of postoperative liver failure (4% vs. 0, p = 0.002), and worse long-term survival versus patients without jaundice (median OS, 10.4 vs. 27.1 months, p < 0.001). Preoperative biliary drainage was performed for the majority of jaundiced patients (77.0%) and was associated with decreased risk of postoperative liver failure (1.3% vs. 13.0%, p = 0.041); preoperative biliary drainage failed to improve long-term survival (median OS, 10.2 months vs. 12.0 months, p = 0.679). On multivariable analysis, R0 resection (17.5 vs. 7.6 months, p < 0.001) and adjuvant therapy (15.6 vs. 6.6 months, p = 0.027) were associated with improved long-term survival among jaundiced patients. ConclusionsWhile preoperative biliary drainage of jaundiced GBC patients decreased the risk of postoperative liver failure, it did not impact long-term outcomes. Rather, preoperative jaundice was associated with a lower chance at R0 resection and worse long-term survival.

Laparoscopic right hemihepatectomy following a novel optimized portal vein embolization: a video case report

BackgroundThis article is the first report of laparoscopic major hepatectomy of Hepatocellular carcinoma (HCC) following optimized portal vein embolization (oPVE).Case presentationThe patient was diagnosed with a single 3 × 3.5 cm HCC located in segment 5 and 8 detected by enhanced computed tomography and magnetic resonance imaging. The lesion was adjacent to the right anterior and posterior portal veins, making it difficult to confirm the adequate liver functional remnant volume, surgical margin and R0 resection. In addition, the liver cirrhosis induced by a long history of chronic hepatitis B virus increased the potential risk of postoperative liver failure and refractory ascites. Therefore, we conducted a laparoscopic surgery following oPVE, by which the safe tumor margin was ensured and the outcome of the surgery was improved. The patient was discharged on the seventh day after the surgery. The AFP gradually decreased to a normal level during the 90-day follow-up.ConclusionThis case report demonstrates that, in experienced hands for selected patients, laparoscopic hepatectomy after portal vein embolization is feasible and may be an alternative to open liver resection.

Preoperative morphometric measurements of liver vasculature to predict postoperative liver failure: bicentric study.

Patients that require major liver resection for various hepatic diseases have a high risk of postoperative liver failure if the remaining postoperative liver is not adequate. Preoperative volumetry of the future liver remnant is not a strong predictor of postoperative liver failure, as function does not always correlate with volume. Our study proposed a new indicator of postoperative liver failure based on preoperative ratio of the diameter of the portal vein (inflow) and the hepatic vein (outflow), which are more predictive of postoperative liver failure than standard volumetry.

Liver resection for perihilar cholangiocarcinoma: Impact of biliary drainage failure on postoperative outcome. Results of an Italian multicenter study

BackgroundPreoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial. MethodsThis is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage. ResultsOf the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P = .003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P = .002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality. ConclusionFailure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers’ experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality.

Multimodal treatment strategies for colorectal liver metastases.

Colorectal cancer is the third most common cancer worldwide. Half of CRC patients develop liver metastases during the course of the disease, with a 5-year survival rate close to zero in the absence of therapy. Surgical resection remains the only possible curative option, and current guidelines recommend adjuvant chemotherapy, resulting in a 5-year survival rate exceeding 50%. Neoadjuvant systemic therapy is not indicated in cases with simple resection but should be offered to all patients with extensive bilobar disease. Personalised systemic treatment is essential to convert upfront non-resectable lesions to resectable ones. Anatomical resections, non-anatomical resections and two-stage hepatectomies can be performed though open or minimally invasive (laparoscopic or robotic) surgery. The extent of a hepatic resection is limited by the risk of postoperative liver failure due to a too small liver remnant, inflow or outflow obstruction or insufficient biliary drainage. About 75% of patients are diagnosed with non-resectable liver metastases not amenable to a standard upfront resection. In recent years, effective therapeutic approaches have revolutionised liver surgery and new strategies have enabled the conversion of primarily non-resectable metastatic disease for resection. These strategies include oncological and surgical therapies, as well as combinations of the two. From an oncological perspective, colorectal liver metastases&nbsp; may be treated by systemic chemotherapy or immunotherapy, or selective intra-hepatic arterial infusion chemotherapy, depending on the extent of the disease and the mutational status. In surgery, we often apply two-stage strategies using portal vein occlusion, such as portal vein embolisation or ligation, or complex two-stage hepatectomy such as associating liver partition and portal vein ligation for staged hepatectomy. Other additive tools to reach curative resection are tumour ablations (electroporation, microwave or radiofrequency). The role of stereotactic radiation of liver metastases is not yet well defined. Modern radiation techniques, including image guidance, breath hold and gating, were only introduced for a larger patient population in recent years. Therefore, prospective studies with larger patient cohorts are still pending. Over the last decade, liver transplantation has gained increasing attention in selective cases of non-resectable colorectal liver metastases, with promising cohort studies, but definitive recommendations must await the results of ongoing randomised controlled trials. The optimal treatment of patients with colorectal liver metastases requires the timely association of various strategies, and all cases must be discussed at multidisciplinary team conferences. While colorectal liver metastases was a uniformly lethal condition a few decades ago, it has become amenable to curative therapies, with excellent quality of life in many scenarios. This review reports on up-to-date treatment modalities and their combinations in the treatment algorithm of colorectal liver metastases. &nbsp; &nbsp.

Resection of Retro-Hepatic Vena Cava (RHVC) En-bloc with Caudate Lobe without Vascular Exclusion for a Low Grade Leiomyosarcoma of Inferior Vena Cava

BackgroundLeiomyosarcomas (LMS) of the inferior vena cava (IVC) originate in the retrohepatic (RHVC) portion in 15% of cases.1 Due to complex anatomy and need to preserve venous outflow from the infra-diaphragmatic viscera, the operation may require total vascular exclusion, veno-venous bypass and hypothermic liver resections.2,3 In this video, virtual planning of the operation allowed a parenchyma-sparing radical resection in a patient with limited liver reserve.MethodsA 12-cm LMS of RHVC invading the entire segment 1 (i.e., Spiegel’s lobe, paracaval portion, and caudate process) was diagnosed in a man with metabolic steato-hepatitis (BMI: 34). He had no response to previous chemotherapy. Major hepatectomy was excluded considering the high risk of postoperative liver failure. 3D-reconstruction of regional anatomy allowed planning of a parenchymal-sparing, en bloc resection of tumor, RHVC, and caudate lobe while avoiding hilar and suprahepatic venous clamping.ResultsThe operation strategy relied on the en bloc separation of caudate lobe, RHVC, and tumor from the hepatic veins confluence and the posterior segments after complete mobilization of the liver. Vessel loop-assisted hanging maneuver, encircling tumor, and RHVC with superimposed 3D-reconstructions guided the parenchymal transection, while preserving the middle hepatic vein outflow. RHVC was replaced with prosthetic material.ConclusionsComplex resection of primary tumor of the IVC en bloc with caudate lobe and RHVC can be attempted in chronic liver diseases at-risk of postoperative failure. Preservations of transhepatic flow and liver function depends on tumor size and preservation of noninvaded hepatic-veins confluence. Preoperative virtual 3D reconstruction is crucial in surgical planning.

ALPPS como opción quirúrgica en terapia reversa aplicado al tratamiento de las metástasis hepáticas del cáncer rectal sincrónico

The risk for postoperative liver failure is the most important limitation for the treatment of patients with primary or secondary liver cancer. Among the different strategies used to increase resectability in liver tumors, a technique known as ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) was developed for patients with tumors previously considered unresectable.We report the case of a male patient referred to our center with a diagnosis of synchronous multiple liver metastases of colorectal cancer considered unresectable who underwent ALPPS using liver-first reverse approach.

"Zoom Resection": A Two-Step Wedge Liver Resection Technique to Resect Deep Tumors and Spare Parenchyma

In certain cases, huge liver resections are required to deal with deep tumors located near vascular pedicles. However, this implies a higher risk of postoperative liver failure and mortality. Liver parenchyma sparing techniques play an essential role in decreasing these risks. In November 2018, our surgical team reported a new two-step wedge liver resection technique to resect deep tumors in an easy way. Although it was a case report, more patients have already been successfully operated with this approach since then. Regarding the technique itself, intraoperative ultrasound is a very important tool employed to plan and guide both steps of the procedure. Initially, we put stitches and resect a cylindrical piece of normal liver parenchyma above the deep tumor. This way, we can "superficialize" the tumor. After that, we place stitches on the future specimen and resect it in the same way it is done with superficial metastases. The main advantage of this procedure is the clear sight and vascular control that can be achieved in those cases in which the tumor is close to vascular pedicles. As a result, the bigger the chance of preserving vascular pedicles, the bigger the chance of sparing parenchyma as well. We have named this procedure “zoom resection” because its dynamics is similar to that of the photograph camera telescopic system.

Reconstruction of the middle hepatic vein using a vein graft from the resected portion of the liver

BackgroundThe middle hepatic veins are often infiltrated by intrahepatic cholangiocarcinoma. Reconstruction of the hepatic vein plays a critical role in preserving more of the residual liver volume and reducing the risk of postoperative liver failure in extreme hepatectomy. We here report a novel way to reconstruct middle hepatic vein by using vessel grafts from wasted liver.Case presentationCase 1: A 64-year-old man was diagnosed with intrahepatic cholangiocarcinoma. The bifurcation and left branch of the portal vein were stenosed, and the root of the middle hepatic vein was infiltrated by the tumor. An extended left hepatectomy was performed, the portal vein was resected and reconstructed, and the middle hepatic vein was reconstructed by anastomosing the proximal left hepatic vein to the distal middle hepatic vein. Case 2: A 69-year-old woman was diagnosed with intrahepatic cholangiocarcinoma. The tumor was located in the left lobe of the liver and the left and middle hepatic veins were infiltrated by the tumor. An extended left hepatectomy was performed, and the left portal vein was used as a vein graft to reconstruct the middle hepatic vein. Both of the two patients’ postoperative ultrasound showed vessel graft patency.ConclusionUsing a vein graft from the resected portion of the liver to reconstruct the middle hepatic vein was a useful technique and showed good result.

Combined extensive liver resections in patients with locally advanced hepatocellular cancer – clinical cases

Currently the main way of curable treatment of hepatocellular carcinomas (HCC)* is a liver resection. Candidates for surgery are patient with good score of liver function (Child-Pugh A group), without destruction of great vessels and distant metastases. Hemihepatectomy is associated with a high risk of postoperative liver failure (including portal hypertension, cirrhosis, portal vein thrombosis). This reason leads to premature failure of the operation. According to current clinical guidelines, system therapy is more suitable, despite of the lack of reliable data on its effectiveness in such clinical situations. The presented cases may support the selection of advanced hemihepatectomy as a treatment for hepatocellular cancer C stage BCLC classification.

New frontiers in liver resection for hepatocellular carcinoma.

SummaryLiver resection is one of the main curative options for early hepatocellular carcinoma (HCC) in patients with cirrhosis and is the treatment of choice in non-cirrhotic patients. However, careful patient selection is required to balance the risk of postoperative liver failure and the potential benefit on long-term outcomes. In the last decades, improved surgical techniques and perioperative management, as well as better patient selection, have enabled the indications for liver resection to be expanded. In this review, we aim to describe the main indications for liver resection in the management of HCC, its role compared to percutaneous ablation and liver transplantation in the therapeutic algorithm, as well as the recent advances in liver surgery that could be used to improve the prognosis of patients with HCC.

Current status of associating liver partition and portal vein ligation for staged hepatectomy in treatment of liver metastasis of colorectal cancer

At present,radical resection remains the best treatment strategy for liver metastasis of colorectal cancer,and patients with large or multiple tumors often face the problem of insufficient residual liver volume after hepatectomy,which may lead to serious complications including liver failure after surgery. Associating liver partition and portal vein ligation for staged hepatectomy( ALPPS) is a novel two-step hepatectomy that allows rapid proliferation of the residual liver after primary surgery and can improve the resectability of liver tumors and reduce the risk of postoperative liver failure. Although ALPPS can achieve R0 resection or tumors and prolong patients' survival time,there are still controversies over its application due to high incidence rates of complications and mortality rate. With reference to related studies in China and foreign countries,this article reviews the current application status and clinical value of ALPPS in liver metastasis of colorectal cancer.

The technique and outcomes of central hepatectomy by the Glissonian suprahilar approach

IntroductionCentral hepatectomy (CH) is technically challenging and seldom-used to treat centrally located tumors. However, CH is a parenchyma-sparing resection that may decrease the risk of postoperative liver failure. This retrospective study presents our technique of CH and assesses the outcomes. MethodsAll CH performed in our department over two decades (1997–2017) were identified. Indications and short-term outcomes were compared between the two decades. Long-term outcomes were assessed. ResultsSixty-four patients underwent CH using a suprahilar approach for hepatocellular carcinoma (HCC: n = 30), metastasis (n = 23), intrahepatic cholangiocarcinoma (IHCCA: n = 9) or other diseases (n = 2). CH represented 6% of 1004 major hepatectomies, (7.4% (n = 35) before 2007 vs 5.4% (n = 29) after 2007). The mean operating time was 219 ± 56 min. A perioperative blood transfusion was required in 14 patients (22%). Intraoperative bile duct injuries occurred in 5 patients (8%), and they were repaired. One patient died postoperatively (1,5%). Ten patients (16%) experienced a major complication. Nine patients (14%) suffered from bile leakage, of which 6 healed spontaneously. Only one patient had low grade liver failure. The R0-resection rate was 69%. After 2007, there were no bile duct injuries (0/29 vs 5/35, p < 0.05), and the average hospital stay was shorter but not significantly (11 vs 14 days). Actuarial 5-year survival was 56% for HCC patients and 34% for those with colorectal metastasis ConclusionsCH is associated with significant biliary morbidity and may increase positive surgical margins. Nevertheless, it should be recommended in selected patients to avoid the risk of postoperative liver failure.

Safety and efficacy of transjugular intrahepatic portosystemic shunt combined with palliative treatment in patients with hepatocellular carcinoma.

BACKGROUNDThere is a close relationship between cirrhosis and hepatocellular carcinoma (HCC). Transjugular intrahepatic portosystemic shunt (TIPS) has good clinical effect in treating the complication of portal hypertension. However, because of the risk of postoperative liver failure, severe complications, and low survival rate for HCC, TIPS is contraindicated in patients with portal hypertension and liver cancer. We studied a large cohort of patients with cirrhosis and HCC who underwent TIPS for recurrent variceal bleeding and/or ascites.AIMTo assess the safety, efficacy, and survival rate in patients with HCC who underwent TIPS.METHODSGroup A comprised 217 patients with HCC and portal hypertension who underwent the TIPS procedure between 1999 and 2014. After TIPS deployment, these patients received palliative treatment for HCC. Group B comprised a cohort of 136 HCC patients with portal hypertension who did not undergo TIPS placement. Group B received palliative treatment for HCC plus medical therapy for portal hypertension. The clinical outcomes and survival rate were assessed.RESULTSIn Group A, the primary technical success rate was 97.69% for TIPS placement, and no severe procedure-related complications of TIPS placement were reported. The control of variceal bleeding (VB) within 1 mo did not differ significantly between the groups (P = 0.261). Absorption of refractory ascites within 1 mo, recurrence of VB, and recurrence of refractory ascites differed significantly between the groups (P = 0.017, 0.023, and 0.009, respectively). By comparison, the rate of hepatic encephalopathy in Group B was lower than that in Group A (P = 0.036). The 1-, 2-, 3-, 4-, and 5-year survival rates were significantly different between Groups A and B (χ2 = 12.227, P = 0.018; χ2 = 12.457, P = 0.014; χ2 = 26.490, P = 0.013; χ2 = 21.956, P = 0.009, and χ2 = 24.596, P = 0.006, respectively). The mean survival time was 43.7 mo in Group A and 31.8 mo in Group B. Median survival time was 50.0 mo in Group A and 33.0 mo in Group B. Mean and median survival differed significantly between the two groups (P = 0.000, χ2 = 35.605, log-rank test). The mortality rate from VB in Group A was low than that in Group B (P = 0.006), but the rates of hepatic tumor, hepatic failure, and multiorgan failure did not differ significantly between the two groups (P = 0.173, 0.246 and 0.257, respectively).CONCLUSIONTIPS combined with palliative treatment is safe and effective for portal hypertension in patients with HCC.

The preoperative fibrosis score 4 predicts posthepatectomy liver failure in patients with hepatocellular carcinoma

Introduction and ObjectivesThe fibrosis score 4 (FIB-4) has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. This study investigates the impact of preoperative FIB-4 on postoperative liver failure of patients with hepatocellular carcinoma (HCC). Materials and methodsData from 205 patients who underwent curative resection for HCC were retrospectively analyzed. The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the FIB-4. Univariate analysis and multivariate analysis were performed to identify risk factors for postoperative liver failure. The clinical outcomes were compared between patients with high FIB-4 and low FIB-4. ResultsThe optimal cutoff value of the FIB-4 was set at 5.92 for postoperative liver failure according to ROC curve. By univariate and multivariate analysis, the number of resected segments, FIB-4, and model for end-stage liver disease score were identified as independent risk factors for postoperative liver failure. Patients with preoperative FIB-4>5.92 had poorer liver function and higher occurrence of postoperative liver failure. ConclusionsPreoperative FIB-4 was associated with postoperative liver failure. Patients with preoperative FIB-4>5.92 carry a high risk of postoperative liver failure.

Surgery for Hilar cholangiocarcinoma: the Newcastle upon Tyne Liver Unit experience

Hilar cholangiocarcinoma (HCCA) arises from the confluence of the common hepatic duct and has a poor prognosis. If resectable, an extended left (eLH) or right hemihepatectomy (eRH) is usually required to provide oncological clearance. We reviewed outcomes for patients with HCCA managed at our centre. Electronic records of patients referred to our centre for HCCA were retrospectively reviewed. The Kaplan–Meier method was used to estimate overall survival (OS) with the log rank test used for significance (p   0.05). Patients undergoing an eLH for HCCA have significantly better long-term outcomes compared to those undergoing eRH, independent of other pathological variables. The functional liver remnant (FLR) is usually smaller following eRH, resulting in a higher risk of post-operative liver failure. Combining CT volumetry with PVE may result in better prediction and optimisation of the FLR in the context of eRH for HCCA. An extended left hemihepatectomy is an independent predictor of survival; investigation into the precise interaction between left- and right-sided resections and pre- and post-embolization liver volume is warranted.