Incidence and Predictors of Textbook Outcome after Minimally Invasive Esophagectomy for Cancer: A Two-Center Study.

PURPOSE: The textbook outcome (TBO), a multidimensional indicator that reflects an optimal perioperative course, has emerged as a significant prognostic variable in surgical oncology. Our study aimed to assess the occurrence and determinants of TBO following minimally invasive esophagectomy (MIE) for cancer. METHODS: A total of 945 patients who had undergone MIE at two high-volume centers between 2008 and 2022 were analyzed. Multivariable logistic regression analysis was applied to identify the independent predictors of TBO. The potential selection bias associated with choosing between different MIE techniques-namely, robotic esophagectomy (RE) and video-assisted thoracoscopic esophagectomy (VATE)-was addressed by applying inverse probability of treatment weighting (IPTW). RESULTS: TBO was realized in 46.6% of cases (n = 440), correlating with markedly better overall and disease-free survival. Multivariable analysis showed that treatment with RE (odds ratio (OR) = 1.527; 95% confidence interval (CI) = 1.149-2.028) was associated with a higher likelihood of achieving TBO, whereas a Charlson Comorbidity Index (CCI) of 2 or higher showed an opposite association (CCI2: OR = 0.687, 95% CI = 0.483-0.977; CCI ≥ 3: OR = 0.604, 95% CI = 0.399-0.915). The advantage of RE in attaining a higher rate of TBO, compared to VATE, remained statistically significant after applying IPTW, with rates of 53.3% for RE and 42.2% for VATE. Notably, RE contributed to a greater probability of thorough lymph node dissection, resection with negative margins, and the avoidance of major complications. CONCLUSION: TBO was realized in 46.6% of the patients who underwent MIE for cancer. Patients with a lower CCI and those who received RE were more likely to achieve TBO.

Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible.

BACKGROUND: A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA. METHODS: Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy-left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS). RESULTS: Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27-34) after left and 23 months (95% CI 20-25) after right liver resection (p < 0.001), and 33 months (95% CI 28-38), 27 months (95% CI 23-32), 25 months (95% CI 21-30), and 21 months (95% CI 18-24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities. CONCLUSIONS: A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred.

Anterior gastric wall anastomosis may lead to lower rate of delayed gastric emptying after minimally invasive Ivor Lewis esophagectomy: a retrospective cohort study.

INTRODUCTION: In minimally invasive esophagectomy, a circular stapled anastomosis is common, but no evidence exists investigating the role of the specific localization of the anastomosis. The aim of this study is to evaluate the impact of an esophagogastrostomy on the anterior or posterior wall of the gastric conduit on the postoperative outcomes. MATERIAL AND METHODS: All oncologic minimally invasive Ivor Lewis procedures, performed between 2017 and 2022, were included in this study. The cohort was divided in two groups: a) intrathoracic esophagogastrostomy on the anterior gastric wall of the conduit (ANT, n = 285, 65%) and b) on the posterior gastric wall (POST, n = 154, 35%). Clinicopathological parameters and short-term outcomes were compared between both groups by retrieving data from the prospective database. RESULTS: Overall, 439 patients were included, baseline characteristics were similar in both groups, there was a higher proportion of squamous cell carcinoma in ANT (22.8% vs. 16.2%, P = 0.043). A higher rate of robotic-assisted procedures was observed in ANT (71.2% vs. 49.4%). Anastomotic leakage rate was similar in both groups (ANT 10.4% vs. POST 9.8%, P = 0.851). Overall complication rate and Clavien-Dindo > 3 complication rates were higher in POST compared to ANT: 53.2% vs. 40% (P = 0.008) and 36.9% vs. 25.7% (P = 0.014), respectively. The rate of delayed gastric emptying (20.1% vs. 7.4%, P < 0.001) and nosocomial pneumonia (22.1% vs. 14.8%, P = 0.05) was significantly higher in POST. CONCLUSION: Patients undergoing minimally invasive Ivor Lewis esophagectomy with an intrathoracic circular stapled anastomosis may benefit from esophagogastrostomy on the anterior wall of the gastric conduit, in terms of lower rate of delayed gastric emptying.

Resection of Colorectal Liver Metastases with Major Vessel Involvement.

BACKGROUND: Treatment of CRLM with major vessel involvement is still challenging and valid data on outcomes are still rare. We analyzed our experience of hepatectomies with resection and reconstruction of major hepatic vessels with regard to operative and perioperative details, histopathological findings and oncological outcome. METHODS: Data of 32 hepatectomies with major hepatic vessel resections and reconstructions were included. Results were correlated with perioperative and oncological outcome. RESULTS: Out of 1236 surgical resections due to CRLM, we performed 35 major hepatic vessel resections and reconstructions in 32 cases (2.6%) during the study period from January 2008 to March 2023. The vena cava inferior (VCI) was resected and reconstructed in 19, the portal vein (PV) in 6 and a hepatic vein (HV) in 10 cases. Histopathological examination confirmed a vascular infiltration in 6/32 patients (VCI 3/17, HV 2/10 and PV 1/6). There were 27 R0 and 5 R1 resections. All R1 situations affected the parenchymal margin. Vascular wall margins were R0. Ninety-day mortality was 0. The median overall survival (OS) for the patient group with vascular infiltration (V1) was 21 months and for the V0 group 33.3 months. CONCLUSION: Liver resections with vascular resection and reconstruction are rare and histological vessel infiltration occurs seldom. In cases with presumed vascular wall infiltration, liver resection combined with major vessel resection and reconstruction can be performed with low morbidity and mortality. We prefer a parenchymal sparing liver resection with vascular resection and reconstruction to achieve negative resection margins, but in technically difficult cases with higher risk for postoperative complications, tumor detachment from vessels without resection is a most reasonable surgical alternative.

Intraoperative Wound Irrigation for the Prevention of Surgical Site Infection After Laparotomy: A Randomized Clinical Trial by CHIR-Net.

Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.

N-cadherin: A diagnostic marker to help discriminate primary liver carcinomas from extrahepatic carcinomas.

Distinguishing primary liver cancer (PLC), namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), from liver metastases is of crucial clinical importance. Histopathology remains the gold standard, but differential diagnosis may be challenging. While absent in most epithelial, the expression of the adherens junction glycoprotein N-cadherin is commonly restricted to neural and mesenchymal cells, or carcinoma cells that undergo the phenomenon of epithelial-to-mesenchymal transition (EMT). However, we recently established N- and E-cadherin expression as hallmarks of normal hepatocytes and cholangiocytes, which are also preserved in HCC and iCCA. Therefore, we hypothesized that E- and/or N-cadherin may distinguish between carcinoma derived from the liver vs carcinoma of other origins. We comprehensively evaluated E- and N-cadherin in 3359 different tumors in a multicenter study using immunohistochemistry and compared our results with previously published 882 cases of PLC, including 570 HCC and 312 iCCA. Most carcinomas showed strong positivity for E-cadherin. Strong N-cadherin positivity was present in HCC and iCCA. However, except for clear cell renal cell carcinoma (23.6% of cases) and thyroid cancer (29.2%), N-cadherin was only in some instances faintly expressed in adenocarcinomas of the gastrointestinal tract (0%-0.5%), lung (7.1%), pancreas (3.9%), gynecological organs (0%-7.4%), breast (2.2%) as well as in urothelial (9.4%) and squamous cell carcinoma (0%-5.6%). As expected, N-cadherin was detected in neuroendocrine tumors (25%-75%), malignant melanoma (46.2%) and malignant mesothelioma (41%). In conclusion, N-cadherin is a useful marker for the distinction of PLC vs liver metastases of extrahepatic carcinomas (P < .01).

Predicting futility of upfront surgery in perihilar cholangiocarcinoma: Machine learning analytics model to optimize treatment allocation.

BACKGROUND: While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. METHODS: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome. RESULTS: A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. CONCLUSIONS: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features.

Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial.

PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.

Surgical Education.

This paper summarizes the proceedings of the joint European Surgical Association ESA/American Surgical Association symposium on Surgical Education that took place in Bordeaux, France, as part of the celebrations for 30 years of ESA scientific meetings. Three presentations on the use of quantitative metrics to understand technical decisions, coaching during training and beyond, and entrustable professional activities were presented by American Surgical Association members and discussed by ESA members in a symposium attended by members of both associations.

Reduced Lipid Peroxidation Predicts Unfavorable Prognosis in Hepatocellular Carcinoma, but Not Intrahepatic Cholangiocarcinoma.

Primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a significant contributor to cancer-related mortality worldwide. Oxidative stress and lipid peroxidation play a key role in chronic liver diseases and have been shown to be pivotal for tumor initiation and progression. 4-hydroxy-nonenal (4-HNE), one of the major mediators of oxidative stress and a well-established biomarker for lipid peroxidation, can act as a signal transducer, inducing inflammation and exerting carcinogenic effects. However, the role of 4-HNE in primary liver cancer remains poorly explored. In this study, we investigated 4-HNE levels in 797 liver carcinomas, including 561 HCC and 236 iCCA, by immunohistochemistry. We then correlated 4-HNE levels with comprehensive clinical data and survival outcomes. In HCC, lower expression levels of 4-HNE were associated with vascular invasion, a high tumor grade, a macrotrabecular-massive HCC subtype, and poor overall survival. Concerning iCCA, large duct iCCA showed significantly higher 4-HNE levels when compared to small duct iCCA. Yet, in iCCA, 4-HNE levels did not correlate with known prognostic parameters or survival outcomes. To conclude, in HCC but not in iCCA, low amounts of 4-HNE predict unfavorable survival outcomes and are associated with aggressive tumor behavior. These findings provide insights into the role of 4-HNE in liver cancer progression and may enable novel therapeutic strategies.

Gut Microbiota in Diagnosis, Therapy and Prognosis of Cholangiocarcinoma and Gallbladder Carcinoma-A Scoping Review.

Cancers of the biliary tract are more common in Asia than in Europe, but are highly lethal due to delayed diagnosis and aggressive tumor biology. Since the biliary tract is in direct contact with the gut via the enterohepatic circulation, this suggests a potential role of gut microbiota, but to date, the role of gut microbiota in biliary tract cancers has not been elucidated. This scoping review compiles recent data on the associations between the gut microbiota and diagnosis, progression and prognosis of biliary tract cancer patients. Systematic review of the literature yielded 154 results, of which 12 studies and one systematic review were eligible for evaluation. The analyses of microbiota diversity indices were inconsistent across the included studies. In-depth analyses revealed differences between gut microbiota of biliary tract cancer patients and healthy controls, but without a clear tendency towards particular species in the studies. Additionally, most of the studies showed methodological flaws, for example non-controlling of factors that affect gut microbiota. At the current stage, there is a lack of evidence to support a general utility of gut microbiota diagnostics in biliary tract cancers. Therefore, no recommendation can be made at this time to include gut microbiota analyses in the management of biliary tract cancer patients.

Computer-assisted intraoperative 3D-navigation for liver surgery: a prospective randomized-controlled pilot study.

Background: Liver surgery is the standard of care for primary and many secondary liver tumors. Due to variability and complexity in liver anatomy preoperative imaging is necessary to determine resectability and for planning the surgical strategy. In the last few years, computer-assisted resection planning has been introduced in liver surgery. Aim of this trial was the evaluation of computer-assisted three-dimensional (3D)-navigation for liver surgery. Methods: This study was a prospective randomized-controlled pilot trial and patients were randomized in navigated or non-navigated group. Primary end point was the quotient of intraoperative resected volume and planned resection volume. Secondary end points included operation time, resection margin and postoperative complications. 3D reconstructions were performed with MeVis Distant Services (MeVis AG, Bremen, Germany). The navigation system CAS-One Liver (CAScination AG, Bern, Switzerland) was used for intraoperative computer-assisted 3D-navigation. Results: The data of 16 patients with 20 liver tumors were used in this analysis. Of these, 8 liver tumors were resected with the utilization of intraoperative navigation. Two postoperative complications were classified grade IIIa or higher. There was no difference in duration of operation (189 vs. 180 min, P=0.970), rate of postoperative complications (n=1 vs. n=1, P=0.696) and length of hospital stay (9 vs. 7 days, P=0.368) between the two groups. Minimal resection margin (0.15 vs. 0.40 cm, P=0.384) and quotient of planned to intraoperative resection volume (0.94 vs. 1.11, P=0.305) were also similar. Conclusions: Intraoperative navigation is a technology that can be safely used during liver resection. Surgical accuracy is not yet superior to the current standard of intraoperative orientation. Further technological advances with suitable deformation algorithms and augmented reality systems will enable a further improvement of the technical feasibility.

Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.

BACKGROUND: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. METHODS: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. RESULTS: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. CONCLUSION: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.

[Evidence, Availability and Future Visions in Simulation in General and Visceral Surgery]. / Evidenz, Verfügbarkeit und Zukunftsvisionen der Simulation in der Allgemein- und Viszeralchirurgie.

Practice makes perfect - a saying that everyone has certainly heard. Surgeons of all levels of training can demonstrably practice to some extent on simulators. This training outside the operating theatre and independent of patients makes sense, both ethically and financially. Although the effectiveness of simulation in surgery has been proven several times, simulation training is not a mandatory part of surgical specialist training in Germany. Simulation covers a very wide range in terms of application, effort and costs. This review is intended to give an overview of the systems and their areas of application and the target group. The focus lies on the commonly available systems and possible advantages and disadvantages. Practical skills are in the foreground and all three pillars of general and visceral surgery - conventional techniques, laparoscopy and robotics - are taken into account. However, simulators alone do not achieve cost-benefit effectiveness. The full potential of such an investment can only be exploited with a site-specific, structured training concept in which simulation training according to the post-graduate year and appropriate allocation to surgeries in the operating room are closely interlinked. It should always be possible to train basic skills on site. The significant additional costs for complex simulation systems are possible, depending on the financial resources, or should be purchased in a network or for national courses. The techniques of immersive virtual reality in combination with artificial intelligence and deformation algorithms will certainly play a decisive role for the future of simulation, whereby the use of the available systems must be a primary goal. The integration of simulation into specialist training should be striven for, not least in order to justify the costs.

The Cellular and Humoral Immune Response to SARS-CoV-2 Messenger RNA Vaccines Is Significantly Better in Liver Transplant Patients Compared with Kidney Transplant Patients.

Patients after organ transplantation have impaired immune response after vaccination against the SARS-CoV-2 virus. So far, published studies have reported quite different response rates to SARS-CoV-2 vaccination, ranging from 15-79% in liver and kidney transplant recipients. Up to one year after the first vaccine dose, we analyzed the humoral and cellular immune response of 21 liver transplant (LTX) patients after vaccination with mRNA vaccines compared with 28 kidney transplant (KTX) patients. We evaluated IgG against the SARS-CoV-2 spike protein as well as SARS-CoV-2 specific T cells using an ELISpot assay that detected IFN-γ- and/or IL-2-expressing T cells. We found a cellular and/or humoral immune response in 100% of the LTX patients compared with 68% of the KTX patients. Antibody titers against the spike protein of SARS-CoV-2 were significantly higher in the LTX group, and significantly more LTX patients had detectable specific IL-2-producing T cells. The immunosuppression applied in our LTX cohort was lower compared with the KTX cohort (14% triple therapy in LTX patients vs. 79% in KTX patients). One year after the first vaccination, breakthrough infections could be detected in 41% of all organ transplant patients. None of those patients suffered from a severe course of COVID-19 disease, indicating that a partial vaccination response seemed to offer protection to immunosuppressed patients. The better immune response of LTX patients after SARS-CoV-2 vaccination might be due to less intense immunosuppressive therapy compared with KTX patients.

The Optimal Fluid Strategy Matters in Liver Surgery: A Retrospective Single Centre Analysis of 666 Consecutive Liver Resections.

As optimal intraoperative fluid management in liver surgery has not been established, we retrospectively analyzed our fluid strategy in a high-volume liver surgery center in 666 liver resections. Intraoperative fluid management was divided into very restrictive (<10 m kg-1 h-1) and normal (≥10 mL kg-1 h-1) groups for study group characterization. The primary endpoint was morbidity as assessed by the Clavien-Dindo (CD) score and the comprehensive complication index (CCI). Logistic regression models identified factors most predictive of postoperative morbidity. No association was found between postoperative morbidity and fluid management in the overall study population (p = 0.89). However, the normal fluid management group had shorter postoperative hospital stays (p = <0.001), shorter ICU stays (p = 0.035), and lower in-hospital mortality (p = 0.02). Elevated lactate levels (p < 0.001), duration (p < 0.001), and extent of surgery (p < 0.001) were the most predictive factors for postoperative morbidity. In the subgroup of major/extreme liver resection, very low total (p = 0.028) and normalized fluid balance (p = 0.025) (NFB) were associated with morbidity. Moreover, fluid management was not associated with morbidity in patients with normal lactate levels (<2.5 mmol/L). In conclusion, fluid management in liver surgery is multifaceted and must be applied judiciously as a therapeutic measure. While a restrictive strategy appears attractive, hypovolemia should be avoided.