Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).

BACKGROUND & AIM: We aimed to assess long-term outcome after transplantation of HOPE-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of a HOPE-treated liver transplanted between January 2012 and December 2021. Analyses were stratified for brain-dead (DBD) and circulatory-dead (DCD) donor livers, sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischemic cholangiopathy (IC). RESULTS: We report on 1202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low-risk (10%), 186 as high-risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival for DBD and DCD was 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (logrank p=0.003). Within DBD and DCD-strata, death-censored graft survival was similar among risk groups (logrank p=0.26, p=0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE-treatment has now reached IDEAL-D stage 4, which further supports the implementation of HOPE in routine clinical practice. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of HOPE-treatment of DCD and DBD liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomized controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE-treatment has now reached the final IDEAL-D Stage 4, which further supports the implementation of HOPE in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320.

Partial liver resection alters the bile salt-FGF19 axis in patients with perihilar cholangiocarcinoma: Implications for liver regeneration.

BACKGROUND: Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to evaluate the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR. METHODS: Plasma bile salts, FGF19, and C4 (bile salt synthesis marker) were assessed in patients with pCCA and controls (colorectal liver metastases), before and after resection on postoperative days (PODs) 1, 3, and 7. Hepatic bile salts were determined in intraoperative liver biopsies. RESULTS: Partial liver resection in pCCA elicited a sharp decline in bile salt and FGF19 plasma levels on POD 1 and remained low thereafter, unlike in controls, where bile salts rose gradually. Preoperatively, suppressed C4 in pCCA normalized postoperatively to levels similar to those in the controls. The remnant liver volume and postoperative bilirubin levels were negatively associated with postoperative C4 levels. Furthermore, patients who developed postoperative liver failure had nearly undetectable C4 levels on POD 7. Hepatic bile salts strongly predicted hyperbilirubinemia on POD 7 in both groups. Finally, postoperative bile salt levels on day 7 were an independent predictor of LR. CONCLUSIONS: Partial liver resection alters the bile salt-FGF19 axis, but its derailment is unrelated to LR in pCCA. Postoperative monitoring of circulating bile salts and their production may be useful for monitoring LR.

Effectiveness and safety of computed tomography-guided high-dose-rate brachytherapy in treating recurrent hepatocellular carcinoma not amenable to repeated resection or radiofrequency ablation.

PURPOSE: To assess the efficacy and safety of computed tomography (CT)-guided high-dose-rate HDR) brachytherapy in treating recurrent hepatocellular carcinoma (HCC) not amenable to repeated resection or radiofrequency ablation. MATERIALS AND METHODS: From January 2010 to January 2022, 38 patients (mean age, 70.1 years; SD ± 9.0 years) with 79 nodular and four diffuse intrahepatic HCC recurrences not amenable to repeated resection or radiofrequency ablation underwent CT-guided HDR brachytheapy in our department. Tumor response was evaluated by cross-sectional imaging 6 weeks after CT-guided HDR brachytherapy and every 3 months thereafter. Local tumor control (LTC), progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves (KPCs). Severity of procedure-related complications (PRCs) was classified as recommended by the Society of Interventional Radiology (SIR). RESULTS: Patients were available for MRI evaluation for a mean follow-up of 33.1 months (SD, ±21.6 mm, range 4-86 months; median 29 months). Patients had a mean of 2.3 (SD, ±1.4) intrahepatic tumors. Mean tumor diameter was 43.2 mm (SD, ±19.6 mm). 13 of 38 (34.2%) patients showed local tumor progression after CT-guided HDR brachytherapy. Mean LTC was 29.3 months (SD, ±22.1). Distant tumor progression was seen in 12 patients (31.6%). The mean PFS was 20.8 months (SD, ±22.1). Estimated 1-, 3-, and 5-year PFS rates were 65.1%, 35.1% and 22.5%, respectively. 13 patients died during the follow-up period. Mean OS was 35.4 months (SD, ±21.7). Estimated 1-, 3-, and 5-year OS rates were 91.5%, 77.4% and 58.0%, respectively. SIR grade 1 complications were recorded in 8.6% (5/38) and SIR grade 2 complications in 3.4% (2/58) of interventions. CONCLUSION: CT-guided HDR brachytherapy is a safe and efficient therapeutic option for managing large or critically located HCC recurrences in the remaining liver after prior hepatic resection.

Shining a spotlight on sarcopenia and myosteatosis in liver disease and liver transplantation: Potentially modifiable risk factors with major clinical impact.

Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.

Extended Right Hepatectomy following Clearance of the Left Liver Lobe and Portal Vein Embolization for Curatively Intended Treatment of Extensive Bilobar Colorectal Liver Metastases: A Single-Center Case Series.

BACKGROUND: Two-staged hepatectomy (TSH) including portal vein embolization (PVE) may offer surgical treatment for extensive bilobar colorectal liver metastases (CRLM). This study aimed to investigate the feasibility and outcomes of extended right hepatectomy (ERH) within TSH including PVE for patients with extended CRLM. METHODS: We retrospectively collected data of patients who underwent TSH for extended CRLM between 2015 and 2021 at our institution. Clearance of the left liver lobe (clear-up, CU) associated with PVE was followed by ERH. RESULTS: Minimally invasive (n = 12, 46%, MIH) or open hepatectomy (n = 14, 54%, OH) was performed. Postoperative major morbidity and 90-day mortality were 54% and 0%. Three-year overall survival was 95%. Baseline characteristics, postoperative and long-term outcomes were comparable between MIH and OH. However, hospital stay was significantly shorter after MIH (8 vs. 15 days, p = 0.008). Additionally, the need for intraoperative transfusions tended to be lower in the MIH group (17% vs. 50%, p = 0.110). CONCLUSIONS: ERH following CU and PVE for extended CRLM is feasible and safe in laparoscopic and open approaches. MIH for ERH may result in shorter postoperative hospital stays. Further high-volume, multicenter studies are required to evaluate the potential superiority of MIH.

Short-term postoperative outcomes of lymphadenectomy for cholangiocarcinoma, hepatocellular carcinoma and colorectal liver metastases in the modern era of liver surgery: Insights from the StuDoQ|Liver registry.

INTRODUCTION: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). MATERIALS AND METHODS: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. RESULTS: LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. CONCLUSION: In this multicenter registry study, LAD was found to be associated with an increased risk of liver-specific complications. The highest rate of LAD was observed among robotic liver resections.

Improved outcomes after hypothermic oxygenated machine perfusion in liver transplantation-Long-term follow-up of a multicenter randomized controlled trial.

BACKGROUND: While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS). METHODS: Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival. RESULTS: A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively). CONCLUSIONS: Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation.

Impact of complexity in minimally invasive liver surgery on enhanced recovery measures: prospective study.

BACKGROUND: Adherence to enhanced recovery after surgery (ERAS) protocols is crucial for successful liver surgery. The aim of this study was to assess the impact of minimally invasive liver surgery complexity on adherence after implementing an ERAS protocol. METHODS: Between July 2018 and August 2021, a prospective observational study involving minimally invasive liver surgery patients was conducted. Perioperative treatment followed ERAS guidelines and was recorded in the ERAS interactive audit system. Kruskal-Wallis and ANOVA tests were used for analysis, and pairwise comparisons utilized Wilcoxon rank sum and Welch's t-tests, adjusted using Bonferroni correction. RESULTS: A total of 243 patients were enrolled and categorized into four groups based on the Iwate criteria: low (n = 17), intermediate (n = 81), advanced (n = 74) and expert difficulty (n = 71). Complexity correlated with increased overall and major morbidity rate, as well as longer length of stay (all P < 0.001; standardized mean difference = 0.036, 0.451, 0.543 respectively). Adherence to ERAS measures decreased with higher complexity (P < 0.001). Overall adherence was 65.4%. Medical staff-centred adherence was 79.9%, while patient-centred adherence was 38.9% (P < 0.001). Complexity significantly affected patient-centred adherence (P < 0.001; standardized mean difference (SMD) = 0.420), but not medical staff-centred adherence (P = 0.098; SMD = 0.315). Postoperative phase adherence showed major differences among complexity groups (P < 0.001, SMD = 0.376), with mobilization measures adhered to less in higher complexity cases. CONCLUSION: The complexity of minimally invasive liver surgery procedures impacts ERAS protocol adherence for each patient. This can be addressed using complexity-adjusted cut-offs and 'gradual adherence' based on the relative proportion of cut-off values achieved.

Obstacles to implement machine perfusion technology in routine clinical practice of transplantation: Why are we not there yet?

Machine perfusion of solid human organs is an old technique, and the basic principles were presented as early as 1855 by Claude Barnard. More than 50 years ago, the first perfusion system was used in clinical kidney transplantation. Despite the well-known benefits of dynamic organ preservation and significant medical and technical development in the last decades, perfusion devices are still not in routine use. This article describes the various challenges to implement this technology in practice, critically analyzing the role of all involved stakeholders, including clinicians, hospitals, regulatory, and industry, on the background of regional differences worldwide. The clinical need for this technology is discussed first, followed by the current status of research and the impact of costs and regulations. Considering the need for strong collaborations between clinical users, regulatory bodies, and industry, integrated road maps and pathways required to achieve a wider implementation are presented. The role of research development, clear regulatory pathways, and the need for more flexible reimbursement schemes is discussed together with potential solutions to address the most relevant hurdles. This article paints an overall picture of the current liver perfusion landscape and highlights the role of clinical, regulatory, and financial stakeholders worldwide.

Detrimental impact of immunosuppressive burden on clinical course in patients with Cytomegalovirus infection after liver transplantation.

INTRODUCTION: Cytomegalovirus (CMV)-infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV-IgG-status has been established for risk stratification when choosing various pharmaceutical regimens for CMV-prophylaxis in the last two decades. However, factors influencing course of CMV-infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients. METHODS: All patients that underwent primary LT between 2006 and 2018 at the Charité-Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV-occurrence was conducted, and survival was examined using Kaplan-Meier analysis. RESULTS: Overall, 867 patients were included in the final analysis. CMV-infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV-IgG-status with either positivity had the largest influence on CMV-occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV-infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank < .001). Multivariate analysis confirmed these findings (p = .02). DISCUSSION: CMV-infection remains of clinical importance after LT. Undergone CMV-infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage-dependent impact of immunosuppression (IS) on long-term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients.

Minimal Invasive Versus Open Surgery for Colorectal Liver Metastases: A Multicenter German StuDoQ|Liver Registry-Based Cohort Analysis in Germany.

Objective: To compare the outcome of minimally invasive liver surgery (MILS) to open liver surgery (OLS) for resection of colorectal liver metastases (CRLM) on a nationwide level. Background: Colorectal cancer is the third most common malignancy worldwide. Up to 50% of all patients with colorectal cancer develop CRLM. MILS represents an attractive alternative to OLS for treatment of CRLM. Methods: Retrospective cohort study using the prospectively recorded German Quality management registry for liver surgery. Propensity-score matching was performed to account for variance in the extent of resection and patient demographics. Results: In total, 1037 patients underwent liver resection for CRLM from 2019 to 2021. MILS was performed in 31%. Operative time was significantly longer in MILS (234 vs 222 minutes, P = 0.02) compared with OLS. After MILS, median length of hospital stay (LOS) was significantly shorter (7 vs 10 days; P < 0.001). Despite 76% of major resections being OLS, postoperative complications and 90-day morbidity and mortality did not differ. The Pringle maneuver was more frequently used in MILS (48% vs 40%, P = 0.048). After propensity-score matching for age, body mass index, Eastern Cooperative Oncology Group, and extent of resection, LOS remained shorter in the MILS cohort (6 vs 10 days, P < 0.001) and operative time did not differ significantly (P = 0.2). Conclusion: MILS is not the standard for resection of CRLM in Germany. Drawbacks, such as a longer operative time remain. However, if technically possible, MILS is a reasonable alternative to OLS for resection of CRLM, with comparable postoperative complications, reduced LOS, and equal oncological radicality.

How to Estimate the Probability of Tolerance Long-Term in Liver Transplant Recipients.

BACKGROUND: Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. PATIENTS AND METHODS: In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. RESULTS: The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). CONCLUSION: In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course.

A surgical strategy for intrahepatic cholangiocarcinoma - the hilar first concept.

PURPOSE: The present study assesses long-term overall survival (OS) and disease-free survival (DFS) after curative resection for intrahepatic cholangiocarcinoma (ICCA) depending on resection margin (RM) status and lymph node (LN) status. METHODS: Clinical data of all consecutively resected patients with ICCA at a single high-volume center between 2005 and 2018 were collected. Minimum follow-up was 36 months. Perioperative and long-term oncological outcome was assessed. RESULTS: One hundred ninety-two cases were included in the analysis. Thirty- and 90-day-mortality was 5.2% (n = 10) and 10.9% (n = 21). OS was 26 months with 1-, 2-, and 5-year-OS rates of 72%, 53%, and 26%. One-, 2-, and 5-year-DFS rates were 54%, 42%, and 35% (N0 vs. N1: 29 vs. 9 months, p = 0.116). R1 was not found to be an independent risk factor for reduced survival in the overall cohort (p = 0.098). When differentiating according to the LN status, clear resection margins were significantly associated with increased DFS for N0 cases (50 months vs. 9 months, p = 0.004). For N1 cases, no significant difference in DFS was calculated for R0 compared to R1 cases (9 months vs. 9 months, p = 0.88). For N0 cases, clear resection margins > 10 mm were associated with prolonged OS (p = 0.048). CONCLUSION: For N1 cases, there was no significant survival benefit when comparing R0 versus R1, while the complication rate remained high for the extended resection types. In view of merging multimodal treatment, the hilar first concept assesses locoregional LN status for optimal surgical therapy.

Body composition is associated with disease aetiology and prognosis in patients undergoing resection of intrahepatic cholangiocarcinoma.

BACKGROUND: Body composition alterations are frequent in patients with cancer or chronic liver disease, but their prognostic value remains unclear in many cancer entities. OBJECTIVE: We investigated the impact of disease aetiology and body composition after surgery for intrahepatic cholangiocarcinoma (iCCA), a rare and understudied cancer entity in European and North American cohorts. METHODS: Computer tomography-based assessment of body composition at the level of the third lumbar vertebra was performed in 173 patients undergoing curative-intent liver resection for iCCA at the Department of Surgery, Charité - Universitätsmedizin Berlin. Muscle mass and -composition as well as subcutaneous and visceral adipose tissue quantity were determined semi-automatically. (Secondary) sarcopenia, sarcopenic obesity, myosteatosis, visceral and subcutaneous obesity were correlated to clinicopathological data. RESULTS: Sarcopenia was associated with post-operative morbidity (intraoperative transfusions [p = 0.027], Clavien-Dindo ≥ IIIb complications [p = 0.030], post-operative comprehensive complication index, CCI [p < 0.001]). Inferior overall survival was noted in patients with myosteatosis (33 vs. 23 months, p = 0.020). Fifty-eight patients (34%) had metabolic (dysfunction)-associated fatty liver disease (MAFLD) and had a significantly higher incidence of sarcopenic (p = 0.006), visceral (p < 0.001) and subcutaneous obesity (p < 0.001). Patients with MAFLD had longer time-to-recurrence (median: 38 vs. 12 months, p = 0.025, log-rank test). Multivariable cox regression analysis confirmed only clinical, and not body, composition parameters (age > 65, fresh frozen plasma transfusions) as independently prognostic for overall survival. CONCLUSION: This study evidenced a high prevalence of MAFLD in iCCA, suggesting its potential contribution to disease aetiology. Alterations of muscle mass and adipose tissue were more frequent in patients with MAFLD.

Genetic polymorphisms in interleukin-1ß (rs1143634) and interleukin-8 (rs4073) are associated with survival after resection of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a rare, understudied primary hepatic malignancy with dismal outcomes. Aiming to identify prognostically relevant single-nucleotide polymorphisms, we analyzed 11 genetic variants with a role in tumor-promoting inflammation (VEGF, EGF, EGFR, IL-1B, IL-6, CXCL8 (IL-8), IL-10, CXCR1, HIF1A and PTGS2 (COX-2) genes) and their association with disease-free (DFS) and overall survival (OS) in patients undergoing curative-intent surgery for iCCA. Genomic DNA was isolated from 112 patients (64 female, 48 male) with iCCA. Germline polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism protocols. The IL-1B +3954 C/C (73/112, hazard ratio (HR) = 1.735, p = 0.012) and the IL-8 -251 T/A or A/A (53/112 and 16/112, HR = 2.001 and 1.1777, p = 0.026) genotypes were associated with shorter OS in univariable and multivariable analysis. The IL-1B +3954 polymorphism was also associated with shorter DFS (HR = 1.983, p = 0.012), but this effect was not sustained in the multivariable model. A genetic risk model of 0, 1 and 2 unfavorable alleles was established and confirmed in multivariable analysis. This study supports the prognostic role of the IL-1B C+3954T and the IL-8 T-251A variant as outcome markers in iCCA patients, identifying patient subgroups at higher risk for dismal clinical outcomes.

Prediction of regional lymph node metastasis in intrahepatic cholangiocarcinoma: it's not all about size.

OBJECTIVES: Lymph node metastases (LNM) are frequent in patients with intrahepatic cholangiocarcinoma (iCC) and worsen their prognosis even after surgery. Our aim was to investigate the predictive value of lymph node (LN) short axis, the most common discriminator for identifying LNM in tumor-imaging and to develop a predictive model for regional LNM in iCC taking computed tomography (CT) features of extranodal disease into account. MATERIALS AND METHODS: We enrolled 102 patients with pathologically proven iCC who underwent CT prior to hepatic resection and hilar lymph node dissection (LND) from 2005 to 2021. Two blinded radiologists assessed various imaging characteristics and LN diameters, which were analyzed by bivariate and multivariate logistic regression to develop a prediction model for LNM. RESULTS: Prevalence of LNM was high (42.4 %) and estimated survival was shorter in LN-positive patients (p = 0.07). An LN short axis diameter of ≥ 9 mm demonstrated the highest predictive power for LNM. Three additional, statistically significant imaging features, presence of intrahepatic metastasis (p = 0.003), hilar tumor infiltration (p = 0.003), and tumor growth along the liver capsule (p = 0.004), were integrated into a prediction model, which substantially outperformed use of LN axis alone in ROC analysis (AUC 0.856 vs 0.701). CONCLUSIONS: LN diameter alone proved to be a relevant but unreliable imaging-marker for LNM prediction in iCC. Our proposed prognostic model, which additionally considers intrahepatic metastases and hilar and capsular infiltration, significantly improves discriminatory power. Hilar and capsular involvement might indicate direct tumor extension to lymphatic liver structures.

Robotic versus laparoscopic versus open major hepatectomy - an analysis of costs and postoperative outcomes in a single-center setting.

PURPOSE: In the era of minimal-invasive surgery, the introduction of robotic liver surgery (RS) was accompanied by concerns about the increased financial expenses of the robotic technique in comparison to the established laparoscopic (LS) and conventional open surgery (OS). Therefore, we aimed to evaluate the cost-effectiveness of RS, LS and OS for major hepatectomies in this study. METHODS: We analyzed financial and clinical data on patients who underwent major liver resection for benign and malign lesions from 2017 to 2019 at our department. Patients were grouped according to the technical approach in RS, LS, and OS. For better comparability, only cases stratified to the Diagnosis Related Groups (DRG) H01A and H01B were included in this study. Financial expenses were compared between RS, LS, and OS. A binary logistic regression model was used to identify parameters associated with increased costs. RESULTS: RS, LS and OS accounted for median daily costs of 1,725 €, 1,633 € and 1,205 €, respectively (p < 0.0001). Median daily (p = 0.420) and total costs (16,648 € vs. 14,578 €, p = 0.076) were comparable between RS and LS. Increased financial expenses for RS were mainly caused by intraoperative costs (7,592 €, p < 0.0001). Length of procedure (hazard ratio [HR] = 5.4, 95% confidence interval [CI] = 1.7-16.9, p = 0.004), length of stay (HR [95% CI] = 8.8 [1.9-41.6], p = 0.006) and development of major complications (HR [95% CI] = 2.9 [1.7-5.1], p < 0.0001) were independently associated with higher costs. CONCLUSIONS: From an economic perspective, RS may be considered a valid alternative to LS for major liver resections.

Surgical Approach to Liver Metastases in GEP-NET in a Tertiary Reference Center.

Indications for liver resection in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) vary from liver resection with curative intent to tumor debulking or tissue sampling for histopathological characterization. With increasing expertise, the number of minimally invasive liver surgeries (MILS) in GEP-NET patients has increased. However, the influence on the oncological outcome has hardly been described. The clinicopathological data of patients who underwent liver resection for hepatic metastases of GEP-NET at the Department of Surgery, Charité-Universitätsmedizin Berlin, were analyzed. Propensity score matching (PSM) was performed to compare MILS with open liver surgery (OLS). In total, 22 patients underwent liver surgery with curative intent, and 30 debulking surgeries were analyzed. Disease-free survival (DFS) was longer than progression-free survival (PFS) (10 vs. 24 months), whereas overall survival (OS) did not differ significantly (p = 0.588). Thirty-nine (75%) liver resections were performed as OLS, and thirteen (25%) as MILS. After PSM, a shorter length of hospital stay was found for the MILS group (14 vs. 10 d, p = 0.034), while neither DFS/PFS nor OS differed significantly. Both curative intended and cytoreductive resection of hepatic GEP-NET metastases achieved excellent outcomes. MILS led to a reduced length of hospital, while preserving a good oncological outcome.

Simplifying minimally invasive right hepatectomy.

BACKGROUND: Extrahepatic transection of the right hepatic artery and right portal vein before parenchymal dissection is a widely used standard for minimal invasive right hepatectomy. Hereby, hilar dissection represents a technical difficulty. We report our results of a simplified approach in which the hilar dissection is omitted and the line of dissection is defined with ultrasound. METHODS: Patients undergoing minimally invasive right hepatectomy were included. Ultrasound-guided hepatectomy (UGH) was defined by the following main steps: (1) ultrasound-guided definition of the transection line, (2) dissection of the liver parenchyma according to the caudal approach, (3) intraparenchymal transection of the right pedicle and (4) of the right liver vein, respectively. Intra- and postoperative outcomes of UGH were compared to the standard technique. Propensity score matching was performed to adjust for parameters of perioperative risk. RESULTS: Median operative time was 310 min in the UGH group compared to 338 min in the control group (p = 0.013). No differences were observed for Pringle maneuver duration (35 min vs. 25 min; p = ns) nor postoperative transaminases levels (p = ns). There was a trend toward a lower major complication rate in the UGH group (13 vs. 25%) and a shorter median hospital stay (8 days vs. 10 days); however, both being short of statistical significance (p = ns). Bile leak was observed in zero cases of UGH compared to 9 out of 32 cases (28%) for the control group (p = 0.020). CONCLUSIONS: UGH appears to be at least comparable to the standard technique in terms of intraoperative and postoperative outcomes. Accordingly, transection of the right hepatic artery and right portal vein prior to the transection phase can be omitted, at least in selected cases. These results need to be confirmed in a prospective and randomized trial.