Patients Undergoing Liver Surgery Research Articles

Mapping Tumor Heterogeneity via Local Entropy Assessment: Making Biomarkers Visible

Advanced imaging and analysis improve prediction of pathology data and outcomes in several tumors, with entropy-based measures being among the most promising biomarkers. However, entropy is often perceived as statistical data lacking clinical significance. We aimed to generate a voxel-by-voxel visual map of local tumor entropy, thus allowing to (1) make entropy explainable and accessible to clinicians; (2) disclose and quantitively characterize any intra-tumoral entropy heterogeneity; (3) evaluate associations between entropy and pathology data. We analyzed the portal phase of preoperative CT of 20 patients undergoing liver surgery for colorectal metastases. A three-dimensional core kernel (5 × 5 × 5 voxels) was created and used to compute the local entropy value for each voxel of the tumor. The map was encoded with a color palette. We performed two analyses: (a) qualitative assessment of tumors’ detectability and pattern of entropy distribution; (b) quantitative analysis of the entropy values distribution. The latter data were compared with standard Hounsfield data as predictors of post-chemotherapy tumor regression grade (TRG). Entropy maps were successfully built for all tumors. Metastases were qualitatively hyper-entropic compared to surrounding parenchyma. In four cases hyper-entropic areas exceeded the tumor margin visible at CT. We identified four “entropic” patterns: homogeneous, inhomogeneous, peripheral rim, and mixed. At quantitative analysis, entropy-derived data (percentiles/mean/median/root mean square) predicted TRG (p < 0.05) better than Hounsfield-derived ones (p = n.s.). We present a standardized imaging technique to visualize tumor heterogeneity built on a voxel-by-voxel entropy assessment. The association of local entropy with pathology data supports its role as a biomarker.Graphical

The Ratio of Activin A and Follistatin-Like 3 Is Associated With Posthepatectomy Liver Failure and Morbidity in Patients Undergoing Liver Resection.

Activin A is a key regulator in liver regeneration, but data evaluating its role in humans after hepatic surgery are limited. In this study we explore the predictive role of circulating activin A, its antagonist follistatin-like 3 (FSTL-3), and their ratio for posthepatectomy liver failure (PHLF) and monitor their levels after surgery, to evaluate their role in human liver regeneration. Activin A and FSTL-3 levels were assessed in 59 patients undergoing liver surgery. Using receiver operating characteristic analysis, we evaluated the predictive potential of activin A, FSTL-3, and their ratio. While perioperative dynamics of activin A and FSTL3 were significantly affected by hepatic resection (activin A P= .045, FSTL-3 P= .005), their functionally relevant ratio did not significantly change (P= .528). Neither activin A nor FSTL-3 alone but only their ratio exhibited a significant predictive potential for PHLF (area under the curve: 0.789, P= .038). Patients with low preoperative activin A/FSTL-3 ratio were found to more frequently suffer from PHLF (0.017) and morbidity (0.005). Activin A/FSTL-3 ratio predicts PHLF and morbidity. Its significance in preoperative patient assessment needs to be further validated in larger, independent cohorts.

Imagingbased body composition profiling and outcomes after oncologic liver surgery.

Body composition profiling is gaining attention as a pre-operative factor that can play a role in predicting the short- and long- term outcomes of patients undergoing oncologic liver surgery. Existing evidence is mostly limited to retrospective and single-institution series and in many of these studies, the evaluation of body composition is based on parameters which are derived from CT-scan imaging. Among body composition phenotypes, sarcopenia is the most well studied but this is only one of the possible profiles which can impact the outcomes of oncologic hepatic surgery. Interest has recently grown in studying the effect of sarcopenic obesity, central obesity, or visceral fat amount, myosteatosis, and bone mineral density on -such patients. The objective of this review is to summarize the current evidence on whether imaging-based parameters of body composition have an impact on the outcome of patients undergoing liver surgery for each of the most frequent indications for liver resection in clinical practice: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM).

An algorithm based on the postoperative decrease of albumin (ΔAlb) to anticipate complications after liver surgery

BackgroundPerioperative decrease of albumin (ΔAlb) appeared as a promising predictor of complications after digestive surgery, but its role after liver surgery remains unclear. This study aimed to analyze whether and how ΔAlb can be used to predict complications after liver surgery.MethodsA bicentric retrospective analysis of patients undergoing liver surgery (2010–2016) was performed, following TRIPOD guidelines. The preoperative and postoperative difference of albumin was calculated on POD 0 and defined as ΔAlb. Patients with any missing variable were excluded. The primary endpoint was overall complications according to the Clavien classification. A multiparametric algorithm based on ΔAlb was generated to optimize prediction performance.ResultsA total of 110 patients were analyzed. At least one complication occurred in 66 (60%) patients. Patients with and without complication showed a ΔAlb of 15.8 vs. 9.5 g/L (p<0.001). Area under ROC curve (AUC) of ΔAlb was 0.75 (p<0.01.). The ΔAlb-based algorithm showed an AUC of 0.84 (p<0.01), significantly improving performance (p=0.03). Multivariable analysis identified ΔAlb as independent predictor of complications (HR, 1.12; 95% CI, 1.01–1.07; p = 0.002).ConclusionsΔAlb appeared as a promising predictor independently associated with the risk of complication after liver surgery. The study presents a novel decision-tree based on ΔAlb to anticipate complications.

Frailty Predicts Loss of Independence After Liver Surgery

BackgroundLoss of independence (LOI) is a significant concern in patients undergoing liver surgery. Although the risks of morbidity and mortality have been well studied, there is a dearth of data regarding the risk of LOI. Therefore, this study aimed to assess predictors of LOI after liver surgery. MethodsThis study utilized the National Surgical Quality Improvement Program (NSQIP) data from 2015 to 2018 from a retrospective cohort study of patients undergoing liver resections. LOI was defined as the change from preoperative functional independence to the postoperative discharge requirement in a post-care facility. Frailty was defined using the modified frailty index-5 (mFI-5). ResultsA total of 22,463 patients underwent hepatectomy via the NSQIP during the study period. In total, 22,067 participants were included in the analysis. A total of 4.7% of patients had LOI after surgery and were discharged to a rehabilitation center or nursing facility. mFI-1 was an independent predictor of LOI (OR:2.2 [1.9–4.3]). However, the odds for LOI were higher (OR:5.1[2.5–8.2]) in patients with mFI ≥ 2. ConclusionLOI is an important outcome of liver surgery. Frailty is a predictor of LOI and should be used as a guide to inform patients about the potential outcomes.

Implementation of a patient blood management in an Italian City Hospital: is it effective in reducing the use of red blood cells?

To evaluate the effect of patient blood management (PBM) since its introduction, we analyzed the need for transfusion and the outcomes in patients undergoing abdominal surgery for different types of tumor pre- and post-PBM. Patients undergoing elective gastric, liver, pancreatic, and colorectal surgery between 2017 and 2020 were included. The implementation of the PBM program was completed on May 1, 2018. The patients were grouped as follows: those who underwent surgery before the implementation of the program (pre-PBM) versus after the implementation (post-PBM). A total of 1302 patients were included in the analysis (445 pre-PBM vs. 857 post-PBM). The number of transfused patients per year decreased significantly after the introduction of PBM. A strong tendency for a decreased incidence of transfusion was evident in gastric and pancreatic surgery and a similar decrease was statistically significant in liver surgery. With regard to gastric surgery, a single-unit transfusion scheme was used more frequently in the post-PBM group (7.7% vs. 55% after PBM; p = 0.049); this was similar in liver surgery (17.6% vs. 58.3% after PBM; p = 0.04). Within the subgroup of patients undergoing liver surgery, a significant reduction in the use of blood transfusion (20.5% vs. 6.7%; p = 0.002) and a decrease in the Hb trigger for transfusion (8.5, 8.2–9.5 vs. 8.2, 7.7–8.4 g/dl; p = 0.039) was reported after the PBM introduction. After the implementation of a PBM protocol, a significant reduction in the number of patients receiving blood transfusion was demonstrated, with a strong tendency to minimize the use of blood products for most types of oncologic surgery.

Real-Life Experience of the Prognostic Significance of the Primary Tumor Location on the Timing of Colorectal Liver Metastases: A Retrospective Analysis.

BackgroundNumerous research studies have looked into how the primary tumor location (PTL) affects patients’ prognosis for colorectal cancer (CRC). Our research aimed to investigate the prognostic effects of PTL in patients with synchronous (SM) and metachronous (MM) colorectal cancer liver metastases (CRCLM).Material and methodsFrom 2016 to 2021, we looked back at the records of patients at our institute who were affected by CRCLM.Results109 patients were included, of whom 21.1% received CRCLM resection (R0=73.9%), with 57.7% having left-sided colon cancer (LCC) and 42.2% having right-sided colon cancer (RCC). SM predominated (69.7%). The median duration of follow-up was 21,3 months (95%CI=15,4-25,2). ≥5 hepatic metastases prevailed in the SM group (N=61; 83.5%). 21% of all patients underwent CRCLM resection (R0=78.2%). We observed a double rate of patients unresponsive to standard systemic antineoplastic treatments in the SM group (35.8% vs. 17.9% of the MM group) (p=0.27). We found a significantly longer median overall survival (OS) in patients with MM-LCC compared with the other groups (27.7 months; HR=0.3797; 95%CI=0.19-0.74; p=0.0205). The median OS, regardless of PTL, was higher in the MM group (16,5 months vs. 16,1 months; HR=0,29; 95%CI=0,13-0,67; p=0.0038) as well as progression-free survival (PFS) (11 months vs. 10,2 months; HR=0,61; 95%CI=0,33-1,12; p=0.11). Finally, in patients undergoing liver surgery, a noteworthy median OS was shown to be significantly in favor of patients with metachronous liver metastases from the primary left tumor (37.0 months; HR=0.47; 95%CI=0.11-1.96; p=0.0041).ConclusionsOur real-life study demonstrated that patients with LCC, particularly MM-LCC, have the highest survival and that the timing of CRCLM should be a prognostic factor.

The orange-III study: the use of preoperative laxatives prior to liver surgery in an enhanced recovery programme, a randomized controlled trial.

This study evaluates the effect of preoperative macrogol on gastrointestinal recovery and functional recovery after liver surgery combined with an enhanced recovery programme in a randomized controlled setting. Patients were randomized to either 1 sachet of macrogol a day, one week prior to surgery versus no preoperative laxatives. Postoperative management for all patients was within an enhanced recovery programme. The primary outcome was recovery of gastrointestinal function, defined as Time to First Defecation. Secondary outcomes included Time to Functional Recovery. Between August 2012 and September 2016, 82 patients planned for liver resection were included in the study, 39 in the intervention group and 43 in the control group. Median Time to First Defecation was 4.0 days in the intervention group (IQR 2.8-5.0) and 4.0 days in the control group (IQR 2.9-5.0), P=0.487. Median Time to Functional Recovery was day 6 (IQR 4.0-8.0) in the intervention group and day 5 (IQR 4.0-7.5) in the control group, P=0.752. No significant differences were seen in complication rate, reinterventions or mortality. This randomized controlled trial showed no advantages of 1 sachet of macrogol preoperatively combined with an enhanced recovery programme, for patients undergoing liver surgery.

COVID-19 and Liver Surgery: How the Pandemic Affected an Italian Medium-Volume HBP Center.

IntroductionWhile the COVID-19 pandemic is still ongoing, it is even more evident that victims of the pandemic are not only those who contract the virus, but also the countless patients suffering from other serious diseases (i.e., tumor) who have undergone delayed potentially life-saving surgery due to a lack of beds. Like many hospitals, ours also initially blocked all elective oncologic surgery, but these operations were “recovered” and reintegrated in a relatively short time, thanks to the establishment of COVID-free wards and operating rooms with staff dedicated to oncological surgery. In tis context, our aim is to assess whether and how the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) pandemic has impacted our hepatobiliary surgery unit.MethodsFrom our prospective database, we retrospectively took data from patients undergoing liver surgery in 2018–2019 (pre-COVID) and 2020–2021 (COVID period). Patients admitted to COVID-free wards must necessarily have a negative nasal swab from the previous 24 h.ResultsBetween January 1, 2018, and December 31, 2019 (Group 1), 101 patients were treated; during the pandemic [January 1, 2020, and December 31, 2021 (Group 2)], 126 patients were treated. There was no statistical difference between the groups. The median postoperative hospital stay was 7 days for both groups; 7 patients had major complications (Clavien-Dindo > 3) in Group 1 and 11 in Group 2 (p = 0.795). A total of 4 patients died in Group 1 and 6 during the pandemic (p = 0.754). Tumor burden was significantly greater in Group 2 where nodule size, lymphadenectomy, and extrahepatic disease were significantly greater (p = 0.011, p = 0.004, and p = 0.026, respectively).ConclusionDuring the COVID pandemic, our HPB unit managed to offer a volume of tertiary-center hepatobiliary surgery without a significant impact in terms of length of stay, morbidity, or mortality despite the increase in tumor burden during the pandemic years.

Abstract 2109: Preoperative exercise therapy attenuates the progression of liver metastases following surgical stress by inducing Kupffer cells-mediated anti-tumor trained immunity

Abstract Introduction: Colorectal cancer (CRC) is a devastating disease, causing mortality worldwide, with the majority of the patients dying from hepatic metastasis. Resection of hepatic metastases improves overall disease-free survival. Unfortunately, not all patients have a successful surgical outcome. Pre-operative exercise therapy (PEx) have been demonstrated to be beneficial in the prevention of post-operative complications. Trained immunity in myeloid cells leads to an aggravated long-term inflammatory phenotype upon a secondary stimulation, a process that results from orchestrated metabolic-epigenetic changes. We hypothesize that PEx initially reverts pro-tumorigenic inflammatory responses following surgical stress and maintains an anti-tumor immune microenvironment through modulating Kupffer cells (KCs) with anti-tumor immunity. Methods: 8-week C57BL/6 mice were randomly divided into PEx and sedentary (Sed) groups, mice with PEx run on a motorized treadmill at a speed of 12.5 m/min for 60 min/day, 5 days/week for 4 weeks. 105 MC38 cells were injected directly through portal vein and surgical stress was subjected to a model of partial hepatic ischemia and reperfusion. The tumor progression was determined by bioluminescent imaging weekly. Both hepatic and tumor CD45+ cells from PEx or Sed mice 3 weeks after IR were submitted for single-cell RNA sequencing (scRNA-seq). Results: 4 weeks of PEx significantly reduces metastasis in the liver along 3 weeks after IR, compared with Sed controls. For the scRNA-seq, 11 cell lineages (KCs, monocytes, neutrophils, DCs, TAMs, TANs, B cells, CD4+ T cells, CD8+ T cells, NK cells, and NKT cells) were identified and annotated according to the transcriptomic profile of feature genes expression. Surprisingly, discontinued 4-week-PEx still led to a significant transcriptomic shift in the KCs. 3 clusters from the entire KCs population were unique in PEx mice. In contrast, 2 Clusters were derived from Sed mice. PEx-relevant KCs are enriched in gene expression related to the anti-tumor phenotype, whereas Sed-relevant KCs are enriched in gene expression related to pro-tumor or immunosuppressive phenotype, which suggests that PEx modulates transcriptomic changes in KCs towards an anti-tumor phenotype. Furthermore, with our established ex vivo trained immunity assay, we observe a clear induction of trained immunity in PEx-KCs when co-cultured with MC38 tumor cells, with noticeably higher levels of anti-tumor cytokines interferon (IFN)-γ and TNF-α compared to Sed-KCs. Summary: Our study is one of the first to show that PEx alters the hepatic immune microenvironment by shifting KC to a tumoricidal phenotype. This work offers a rationale for PEx for cancer patients undergoing liver surgery thereby decreasing post-operative metastases and morbidity. Citation Format: Hongji Zhang, Xiang Cheng, Chengli Shen, Meihong Deng, Allan Tsung, Hai Huang. Preoperative exercise therapy attenuates the progression of liver metastases following surgical stress by inducing Kupffer cells-mediated anti-tumor trained immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2109.

Anxiety and depression in older adult patients undergoing elective liver surgery in allopatry medical treatment

Allopatry medical treatment is common in China. However, allopatry medical therapy can result in many problems, including a negative psychological impact on patients. Patients undergoing liver surgery often experience anxiety and depression. To understand the psychological status of older adult patients undergoing surgery better, this study was designed to investigate the incidence of anxiety and depression in older adult patients undergoing elective liver surgery and to analyze factors associated with it in allopatry medical therapy. A total of 173 older adult patients undergoing elective liver surgery were included in the study. Patients were evaluated using the hospital anxiety and depression scale (HADS). The contributing factors affecting the psychological state of older adult patients undergoing elective surgery were analyzed using a linear regression method. The HADS-A (hospital anxiety and depression scale-anxiety). The correlation (scale) score of the older adult patients undergoing elective liver surgery was (8.69 ± 2.38), including 53 asymptomatic patients, 86 suspicious patients, and 34 symptomatic patients. The HADS-D (hospital anxiety and depression scale-depression) score was (8.31 ± 2.90), including 83 asymptomatic patients, 56 suspicious patients, and 34 symptomatic patients. Multivariate analysis showed that residence and complication grade (Clavien–Dindo Classification of Surgical Complications or Accordion Severity Grading System) significantly correlated with the anxiety level of patients undergoing elective surgery. Residence, a requirement of blood transfusion, total transfusion volume, and Accordion complication grade showed a significant correlation with depression in patients undergoing elective surgery. Anxiety and depression in older adult patients undergoing elective liver surgery were common. Regional differences (local patients vs non local patients) and the severity of complications were the risk factors for anxiety and depression in older adult patients undergoing elective liver surgery. Reducing both regional differences and the severity of complications would be beneficial to alleviate the risk of anxiety and depression in older adult patients undergoing elective liver surgery and thus promote their physical and mental health.

Incidence of Liver Resection Following the Introduction of Caseload Requirements for Liver Surgery in Switzerland

BackgroundCentralization of care is an established concept in complex visceral surgery. Switzerland introduced case load requirements (CR) in 2013 in five areas of cancer surgery. The current study investigates the effects of CR on indication and mortality in liver surgery.MethodsThis is a retrospective analysis of a complete national in-hospital data set including all admissions between January 1, 2005, and December 31, 2015. Primary outcome variables were the incidence proportion and the 60-day in-hospital mortality of liver resections. Incidence proportion was calculated as the overall yearly number of liver resections performed in relation to the population living in Switzerland before and after the introduction of CR.ResultsOur analysis shows an increase number of liver resections compared to the period before introduction of CR from 2005–2012 (4.67 resections/100,000) to 2013–2015 (5.32 resections/100,000) after CR introduction. Age-adjusted incidence proportion increased by 14% (OR 1.14 95 CI [1.07–1.22]). National in-hospital mortality remained stable before and after CR (4.1 vs 3.7%), but increased in high-volume institutions (3.6 vs 5.6%). The number of hospitals performing liver resections decreased after the introduction of CR from 86 to 43. Half of the resections were performed in institutions reaching the stipulated numbers (53% before vs 49% after introduction of CR). After implementation of CR, patients undergoing liver surgery had more comorbidities (88 vs 92%).ConclusionThe introduction of CR for liver surgery in Switzerland in 2013 was accompanied by an increase in operative volume with limited effects on centralization of care.

Evaluation of bile sterility in patients undergoing liver resection

&lt;b&gt;Introduction:&lt;/b&gt; Surgery remains the mainstay of treatment for liver tumors. Significant differences in complication rates between liver surgery centers have been reported ranging from 4.1% up to 47.7%. There have been little papers or studies on the impact of bile infection on postoperative complications in patients undergoing surgery for liver cancer. &lt;/br&gt;&lt;/br&gt; &lt;b&gt;Aim:&lt;/b&gt; The aim of our study was to assess the etiology of bile infections in patients following liver resection and to evaluate its impact on complications and perioperative mortality. &lt;/br&gt;&lt;/br&gt; &lt;b&gt;Materials and methods:&lt;/b&gt; The studied material consisted of 69 patients undergoing surgery for liver tumors at the Department of General and Transplant Surgery of the Medical University of Lodz between 2011 and 2013, when the intraoperative bile cultures were available. &lt;/br&gt;&lt;/br&gt; &lt;b&gt; Results:&lt;/b&gt; The intraoperative bile cultures were positive for bacteria in 12 cases (18.75%), while in other cases the bile was sterile (n = 52). In 41.61% of cases, a methicillin-resistant strain was identified. Two patients presented with jaundice, associated with abdominal pain in one patient; other patients complained of abdominal pain only (jaundice: 16.67%; abdominal pain: 91.67%). In both cases, jaundice was not accompanied by any other typical symptoms of cholangitis; also, palliative surgery was performed in both cases. In patients with confirmed bile infection, jaundice was significantly more common (16.67% vs 0.00%; p = 0.033). Patients with sterile bile cultures reported weight loss significantly more often compared to patients with bile infection (26.90% vs 0.00%; p = 0.042). The hospital stay was longer in patients with bile infection (p = 0.138), whereas the hospitalization was significantly longer in patients infected with methicillin-resistant strains compared to both patients with sterile bile and those with bile infection with non-resistant strains. &lt;/br&gt;&lt;/br&gt; &lt;b&gt; Conclusions:&lt;/b&gt; The causes and real incidence of asymptomatic bile infection remain unknown. Routine bile cultures in patients undergoing liver surgery may prevent complications by early modification of antibiotic regime considering the antibiogram, and identification of the most common causes of asymptomatic bile infection may translate to better preoperative antibiotic prophylaxis.

Navigator Nurse within a Fast Track Program of Liver Resections: How to Improve the Healthcare Service and Perioperative Results

Introduction: The introduction into the clinical practice of the navigator nurse (NaNu) to address the task of counselling and short term follow up has this specific goal. The aim of the present study was to investigate the impact of the standardization of the NaNu's role in patients undergoing liver surgery.

Intravenous immunoglobulin is effective in alleviating hepatic ischemia-reperfusion injury: a rat model study.

Hepatic ischemia-reperfusion injury (I/R) is an important factor affecting the prognosis of patients undergoing liver surgery. This study aimed to explore the value of intravenous immunoglobulin (IVIG) in hepatic I/R and its mechanism in a rat model. Forty eight adult male Sprague-Dawley (SD) rats were divided into six groups randomly: (1-2) treated with normal saline (NS) without ischemia or reperfusion; (3-4) treated with NS + 30min ischemia; (5-6) treated with IVIG + 30min ischemia. Rats of group 1/3/5 were euthanized at 12h after operation (sham + NS + 12h, I/R + NS + 12h, I/R + IVIG + 12h group) while group 2/4/6 were euthanized at 24h (sham + NS + 24h, I/R + NS + 24h, I/R + IVIG + 24h group). Interleukin 10 (IL-10), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) were quantified as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Hepatic pathological changes were observed while nuclear factor kappa B p65 (NF-κB p65), Inhibitory Subunit of NF Kappa B Alpha (IKB-alpha) and cleaved caspase-3 were detected. ALT, AST, IL-6, TNF-alpha, NF-κB p65 and cleaved caspase-3 were increased by I/R whereas IL-10 and IKB-alpha were decreased. However, IVIG pretreatment reduced ALT, AST, IL-6, TNF-alpha, NF-κB p65 and cleaved caspase-3, but increased IL-10 and IKB-alpha. IVIG treatment attenuates the infiltration of inflammatory cell and cell apoptosis which were observed in I/R groups. IVIG may alleviate hepatic I/R in rats by inhibiting the classical NF-κB signaling pathway, reducing IL-6, TNF-alpha, promoting IL-10, and inhibiting cell apoptosis.

EP.TH.140Enhanced Recovery in Liver Surgery: Effect on Survival in Patients with Colorectal Liver Metastases

Abstract Aims Enhanced recovery after surgery (ERAS) has shown to reduce perioperative stress and improve short-term postoperative outcomes. However, little is known regarding the effect of ERAS on long-term oncological outcomes. This study aimed to investigate the impact of ERAS on overall survival in patients undergoing liver resection for colorectal liver metastases (CRLM). Methods Between 2006 and 2014, 387 patients underwent liver resection for CRLM at Royal Surrey County Hospital. The ERAS protocol after liver surgery was implemented in 2011. Data regarding patients’ demographics, oncological characteristics, long and short-term postoperative outcomes were obtained from a prospectively maintained institutional database. Comparative analysis was performed between the ERAS and non-ERAS patients. The primary objective was overall survival (OS) and secondary objective included identification of factors affecting OS. Results The groups were similar in terms of demographics, primary and secondary disease oncological characteristics. Intrahepatic recurrence rates were comparable between ERAS and non-ERAS group (30.3% vs 27% p = 0.496). Patients in the ERAS group demonstrated better 3-year survival rates in comparison with the non-ERAS ones (78.2% vs 68%, p = 0.027). Although survival was better at 5-years as well, this did not reach statistical significance (54.2% vs 50%, p = 0.470). The Cox proportional hazards analysis showed that increased length of hospital stay (HR 1.338, 95% CI 1.039-1.723, p = 0.024) and operative time (HR 1.580, 95% CI 1.173-2.128, p = 0.003) were the only parameters associated with increased risk for worse OS. Conclusions ERAS protocol may be associated with improved 3-year survival in patients undergoing liver surgery for CRLM.

Impact of conventional vs. goal-directed fluid therapy on urethral tissue perfusion in patients undergoing liver surgery: A pilot randomised controlled trial.

Although fluid administration is a key strategy to optimise haemodynamic status and tissue perfusion, optimal fluid administration during liver surgery remains controversial. To test the hypothesis that a goal-directed fluid therapy (GDFT) strategy, when compared with a conventional fluid strategy, would better optimise systemic blood flow and lead to improved urethral tissue perfusion (a new variable to assess peripheral blood flow), without increasing blood loss. Single-centre prospective randomised controlled superiority study. Erasme Hospital. Patients undergoing liver surgery. Forty patients were randomised into two groups: all received a basal crystalloid infusion (maximum 2 ml kg-1 h-1). In the conventional fluid group, the goal was to maintain central venous pressure (CVP) as low as possible during the dissection phase by giving minimal additional fluid, while in the posttransection phase, anaesthetists were free to compensate for any presumed fluid deficit. In the GDFT group, patients received in addition to the basal infusion, multiple minifluid challenges of crystalloid to maintain stroke volume (SV) variation less than 13%. Noradrenaline infusion was titrated to keep mean arterial pressure more than 65 mmHg in all patients. The mean intra-operative urethral perfusion index. The mean urethral perfusion index was significantly higher in the GDFT group than in the conventional fluid group (8.70 [5.72 to 13.10] vs. 6.05 [4.95 to 8.75], P = 0.046). SV index (ml m-2) and cardiac index (l min-1 m-2) were higher in the GDFT group (48 ± 9 vs. 33 ± 7 and 3.5 ± 0.7 vs. 2.4 ± 0.4, respectively; P < 0.001). Although CVP was higher in the GDFT group (9.3 ± 2.5 vs. 6.5 ± 2.9 mmHg; P = 0.003), intra-operative blood loss was not significantly different in the two groups. In patients undergoing liver surgery, a GDFT strategy resulted in a higher mean urethral perfusion index than did a conventional fluid strategy and did not increase blood loss despite higher CVP. NCT04092608.

Pharmacological Activation of Nrf2 Enhances Functional Liver Regeneration.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates an array of cytoprotective genes, yet studies in transgenic mice have led to conflicting reports on its role in liver regeneration. We aimed to test the hypothesis that pharmacological activation of Nrf2 would enhance liver regeneration. Wild-type and Nrf2 null mice were administered bardoxolone methyl (CDDO-Me), a potent activator of Nrf2 that has entered clinical development, and then subjected to two-thirds partial hepatectomy. Using translational noninvasive imaging techniques, CDDO-Me was shown to enhance the rate of restoration of liver volume (MRI) and improve liver function (multispectral optoacoustic imaging of indocyanine green clearance) in wild-type, but not Nrf2 null, mice following partial hepatectomy. Using immunofluorescence imaging and whole transcriptome analysis, these effects were found to be associated with an increase in hepatocyte hypertrophy and proliferation, the suppression of immune and inflammatory signals, and metabolic adaptation in the remnant liver tissue. Similar processes were modulated following exposure of primary human hepatocytes to CDDO-Me, highlighting the potential relevance of our findings to patients. Our results indicate that pharmacological activation of Nrf2 is a promising strategy for enhancing functional liver regeneration. Such an approach could therefore aid the recovery of patients undergoing liver surgery and support the treatment of acute and chronic liver disease.

The impact of enhanced recovery program compliance after elective liver surgery: Results from a multicenter prospective national registry

BackgroundThe Enhanced Recovery Program after surgery is a multimodal, evidence-based protocol of care developed to minimize the response to surgical stress. Data on the influence of ERP on outcomes, particularly according to the complexity of liver surgery, are lacking. MethodsA prospective multicenter cohort of patients undergoing liver surgery and exposed to Enhanced Recovery Program from 2016 to 2020 in France was analyzed. High Enhanced Recovery Program compliance was defined as more than 70% of items (15 out of 21). The outcomes were the rate of complications, length of stay, and functional recovery according to Enhanced Recovery Program compliance. ResultsA total of 297 patients were included in the study, and they had 61.9% overall compliance (median = 13 items, interquartile range 11–15). Complications were observed in 32.2% (n = 95) of cases, and the mean length of hospital stay was 7.28 (±7.15) days overall.A longer duration of liver surgery was associated with an increase in the complication rate, while high compliance was independently associated with a reduced risk of complications in the multivariable analysis. ConclusionHigh Enhanced Recovery Program compliance was associated with a lower rate of postoperative complications.

Development of a patient-reported outcome tool for assessing symptom burden during perioperative care in liver surgery: The MDASI-PeriOp-Hep.

Based on the MD Anderson Symptom Inventory (MDASI), we developed a Patient-reported outcomes tool for hepatectomy perioperative care (MDASI-PeriOp-Hep). To establish the content validity, we generated PeriOp-Hep-specific candidate items from qualitative interviews of patients (n=30), and removed items that lacked clinical relevance on the basis of input from panels of patients, caregivers, and clinicians. The psychometric properties of the MDASI-PeriOp-Hep were validated (n=150). The cognitive debriefing and clinical interpretability were assessed to confirm the ease of comprehension, relevance, and acceptability of the tool. Five symptoms specific to hepatectomy (abdominal bloating, tightness, or fullness; abdominal cramping; muscle weakness, instability, or vertigo; constipation; and incisional tightness) were identified as module items to form the MDASI-PeriOp-Hep. The Cronbach αs for symptoms and for interference were 0.898 and 0.861, respectively. The test-retest reliability was 0.887 for all 18 symptom severity items. Compared to other commonly used tools, correlation of MDASI-PeriOp-Hep scores to performance status (all, P<0.001) and to the phase of perioperative care confirmed known-group validity. Convergent validity was excellent against other standard Patient-reported outcomes tools. Cognitive debriefing demonstrated that the MDASI-PeriOp-Hep was an easy to use and understandable tool. For integrating patient-reported outcomes in perioperative patient care, a procedure-specific tool is desirable. The MDASI-PeriOp-Hep is a valid, reliable, concise tool for measuring symptom severity and functional interference in patients undergoing liver surgery.