Jens Mittler

In perihilar cholangiocarcinoma major liver resections are often required to attain oncological radicality, but these approaches are associated with a high perioperative morbidity and mortality. The aim of this study was to assess the outcome of minor resections compared to standard major liver resections. A single-institutional database was queried for all patients undergoing resection for perihilar cholangiocarcinoma between 2008 and 2024. Minor resections were defined as resections of the hilar bifurcation including up to three liver segments, whereas major resections exceeded 3 segments. The primary study endpoint was safety and feasibility of resection represented by 30-day mortality. Secondary endpoints included survival outcomes. The primary outcome was evaluated using logistic regression. Survival outcomes were analysed using Kaplan–Meier method and Cox regression. Additionally, a propensity score matching was conducted, grouping variables by age and Bismuth-Classification. Two hundred sixteen patients underwent resection, 182 in the major resection and 34 in the minor resection group. Patients in the minor resection group were older (71.4 vs. 66.0 years, p = 0.007) and had more comorbidities (Charlson Comorbidity Index: 5.3 vs. 4.7, p = 0.03). After propensity score matching demographic data were balanced between groups. Minor resection was consistently associated with a trend toward lower 30-day mortality rate (2.9% vs. 13.7%, p = 0.057). Intraoperative blood loss requiring blood transfusion and length of surgery were independently associated with 30-day mortality, both of which were significantly lower in the minor resection group. Median overall survival was 30.1 months in the minor resection and 23.9 months in the major resection group ( p = 0.84). Minor resection in perihilar cholangiocarcinoma was associated with a trend towards reduced and acceptable perioperative mortality at the expense of a lower surgical radicality and long-term survival compared to major resections.

Background/Objectives: Salvage hepatectomy with a prolonged anhepatic phase represents a potential life-saving strategy in patients with toxic liver syndrome (TLS) following orthotopic liver transplantation (OLT). Available evidence is limited to small case series. Methods: We retrospectively analyzed all patients undergoing OLT between 2014 and 2024 at a German transplant center. Among 497 patients, 33 required retransplantation, including four patients who underwent salvage hepatectomy due to refractory TLS. Clinical trajectories were analyzed descriptively. Additionally, a structured narrative review of the literature was performed. Results: Median age was 63 years (range 62–67), and median anhepatic time was 38.4 h (range 14.39–71.55). No patient died during the anhepatic phase. One patient died during retransplantation, and another during the postoperative course. Two patients survived long-term without neurological impairment. A literature review identified 30 relevant studies with reported mortality rates exceeding 50%. Conclusions: Salvage hepatectomy with subsequent retransplantation may serve as a life-saving bridge in selected patients with TLS. However, outcomes remain heterogeneous, and evidence is limited. This study provides detailed insights into perioperative physiological trajectories and clinical decision-making, which are insufficiently described in the current literature.

Background: Non-invasive scoring systems for predicting the hepatic venous pressure gradient (HVPG) and, thus, clinically significant portal hypertension (CSPH) have been proposed; the aim of this study was to evaluate the accuracy of these scores in a cohort of patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement and to further analyze patients without a markedly elevated portosystemic gradient (PSG) at the time of the procedure. Methods: We retrospectively analyzed 314 patients who underwent TIPS implantation at our tertiary care center between 2010 and 2022. The diagnostic performance of CT-based scoring systems by Iranmanesh (Score 1) and Kihira (Score 2), as well as laboratory-based scores including MELD (Score 3), FIB-4 (Score 4), and APRI (Score 5), was assessed for detecting a markedly elevated PSG (PSG > 10 mmHg). Additionally, we evaluated whether incorporating the inferior vena cava (IVC) diameter as a surrogate marker of central venous pressure (CVP) improves the accuracy of CT-based scores. Results: Both Scores 1 and 2 showed high sensitivity (89–87%) but low specificity (33–27%). ROC analysis revealed AUC values between 0.65 and 0.62. Laboratory-based scores (Score 3–5) performed poorly with AUCs of 0.57–0.54. Adding IVC diameter as an estimator for CVP to Scores 1 and 2 significantly increased the AUC to 0.74 and 0.76. In Lasso regression, IVC diameter was selected as a significant variable for PSG estimation. Conclusions: CT-based scoring systems showed promise in assessing markedly elevated PSG, but their specificity was low. Including the IVC diameter improved accuracy in detecting elevated PSG in TIPS patients. Future scoring systems should incorporate CVP estimators like the IVC diameter.

Background/Objectives: MVI is a relevant prognostic factor among patients with hepatocellular carcinoma (HCC) receiving liver transplantation (LT). The preoperative assessment of the risk for MVI is relevant to pre-LT patient management and selection. The objective of this study was to create and validate a model to predict microvascular invasion (MVI) based on preoperative variables in the LT setting. Methods: A total of 2170 patients from 11 collaborative centers in Europe, Asia, and the US, who received transplants between 1 January 2000 and 31 December 2017, were enrolled in the study. The entire cohort was split into a training and a validation set (70/30% of the initial cohort, respectively) using random selection. Results: MVI was reported in 586 (27.0%) explanted specimens. Using the training set data, multivariable logistic regression identified three preoperative parameters associated with MVI: α-fetoprotein (lnAFP; odds ratio [OR] = 1.19; 95% confidence interval [CI] = 1.13–1.27), imaging tumor burden score (lnTBS; OR = 1.66; 95%CI = 1.39–1.99), and a fast-track approach before LT due to the availability of a live donation (OR = 1.99; 95%CI = 1.56–2.53). In the validation set, the LT-MVI c-index was 0.74, versus 0.69 for the MVI score proposed by Endo et al. (Brier Skill Score +75%). The new score had a relevant net reclassification index (overall value = 0.61). Stratifying the validation set into three risk categories (0–50th, 51st–75th, and >75th score percentiles), a very good stratification was observed in terms of disease-free (5-year: 89.3, 75.5, and 50.7%, respectively) and overall survival (5-year: 79.5, 72.6, and 53.7%, respectively). Conclusions: The preoperative assessment of MVI using the proposed score demonstrated very good accuracy in predicting MVI after LT.

HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22–1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04–1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35–1.73, p < 0.001), microvascular (HR = 2.37, 95%–CI, 1.87–2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41–4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29–2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54–3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.

Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy, followed by intrahepatic cholangiocarcinoma (ICC). In addition, there is a mixed form for which only limited data are available. The aim of this study was to compare recurrence and survival of the mixed form within the cohorts of patients with HCC and ICC from a single center. Methods: Between January 2008 and December 2020, all patients who underwent surgical exploration for ICC, HCC, or mixed hepatocellular cholangiocarcinoma (mHC-CC) were included in this retrospective analysis. The data were analyzed, focusing on preoperative and operative details, histological outcome, and tumor recurrence, as well as overall and recurrence-free survival. Results: A total of 673 surgical explorations were performed, resulting in 202 resections for ICC, 344 for HCC (225 non-cirrhotic HCC, ncHCC; 119 cirrhotic HCC, cHCC), and 14 for mHC-CC. In addition, six patients underwent orthotopic liver transplant (OLT) in the belief of dealing with HCC. In 107 patients, tumors were irresectable (resection rate of 84%). Except for the cHCC group, major or even extended liver resections were required. Vascular or visceral extensions were performed regularly. Overall survival (OS) was highly variable, with a median OS of 17.6 months for ICC, 26 months for mHC-CC, 31.8 months for cHCC, and 37.2 months for ncHCC. Tumor recurrence was common, with a rate of 45% for mHC-CC, 48.9% for ncHCC, 60.4% for ICC, and 67.2% for cHCC. The median recurrence-free survival was 7.3 months for ICC, 14.4 months for cHCC, 16 months for mHC-CC, and 17 months for ncHCC. The patients who underwent OLT for mHC-CC showed a median OS of 57.5 and RFS of 56.5 months. Conclusions: mHC-CC has a comparable course and outcome to ICC. The cholangiocarcinoma component seems to be the dominant one and, therefore, may be responsible for the prognosis. ‘Accidental’ liver transplant for mHC-CC within the Milan criteria offers a good long-term outcome. This might be an option in countries with no or minor organ shortage.

Portal vein infiltration (PVI) is a typical complication of HCC. Once diagnosed, it leads to classification as BCLC C with an enormous impact on patient management, as systemic therapies are henceforth recommended. Our aim was to investigate whether radiomics analysis using imaging at initial diagnosis can predict the occurrence of PVI in the course of disease. Between 2008 and 2018, we retrospectively identified 44 patients with HCC and an in-house, multiphase CT scan at initial diagnosis who presented without CT-detectable PVI but developed it in the course of disease. Accounting for size and number of lesions, growth type, arterial enhancement pattern, Child–Pugh stage, AFP levels, and subsequent therapy, we matched 44 patients with HCC who did not develop PVI to those developing PVI in the course of disease (follow-up ended December 2021). After segmentation of the tumor at initial diagnosis and texture analysis, we used LASSO regression to find radiomics features suitable for PVI detection in this matched set. Using an 80:20 split between training and holdout validation dataset, 17 radiomics features remained in the fitted model. Applying the model to the holdout validation dataset, sensitivity to detect occurrence of PVI was 0.78 and specificity was 0.78. Radiomics feature extraction had the ability to detect aggressive HCC morphology likely to result in future PVI. An additional radiomics evaluation at initial diagnosis might be a useful tool to identify patients with HCC at risk for PVI during follow-up benefiting from a closer surveillance.

Liver cirrhosis is the most common risk factor for the development of hepatocellular carcinoma (HCC). However, 10 to 15% of all HCC arise in a non-cirrhotic liver. Few reliable data exist on outcome after liver resection in a non-cirrhotic liver. The aim of this single-centre study was to evaluate the outcome of resection for HCC in non-cirrhotic liver (NC-HCC) and to determine prognostic factors for overall (OS) and intrahepatic recurrence-free (RFS) survival. From 2008 to 2020, a total of 249 patients were enrolled in this retrospective study. Primary outcome was OS and RFS. Radiological and pathological findings, such as tumour size, number of nodules, Tumour-, Nodes-, Metastases- (TNM) classification and vascular invasion as well as extent of surgical resection and laboratory liver function were collected. Here, 249 patients underwent liver resection for NC-HCC. In this case, 50% of patients underwent major liver resection, perioperative mortality was 6.4%. Median OS was 35.4 months (range 1–151 months), median RFS was 10.5 months (range 1–128 moths). Tumour diameter greater than three centimetres, multifocal tumour disease, vascular invasion, preoperative low albumin and increased alpha-fetoprotein (AFP) values were associated with significantly worse OS. Our study shows that resection for NC-HCC is an acceptable treatment approach with comparatively good outcome even in extensive tumours.