[Digital applications in prehabilitation before major visceral surgery procedures]. / Digitale Applikationen in der Prähabilitation vor großen viszeralchirurgischen Operationen.

BACKGROUND: Prehabilitation is of becoming of growing interest in the medical specialist societies, especially before major surgical procedures in older and frail patients. The body of evidence in steadily growing. OBJECTIVES: Are there good digital solutions for a remote prehabilitation program at home? METHODS: Narrative review of the evidence and current study activities in analogous and digital prehabilitation. RESULTS: Prehabilitation is becoming increasingly more important in the optimal preparation of patients before major surgical procedures. With the help of tailored programs patients can be improved and the risk of complications can be significantly lowered. With an optimal selection, this is not associated with a deterioration of the prognosis for patients with cancer during the intervention lasting for 3-6 weeks. There is still a lack of results and good evidence from well-designed trials for digital solutions. CONCLUSION: Prehabilitation can be safely implemented in the preparation of patients before major surgical procedures. Digital solutions are currently being developed and tested and could possibly increase the acceptance in the currently intensifying resource shortages.

Predictive value of a novel digital risk calculator to determine early patient outcomes after major surgery: a proof-of-concept pilot study.

BACKGROUND: A structured risk assessment of patients with validated and evidence-based tools can help to identify modifiable factors before major surgeries. The Protego Maxima trial investigated the value of a new digitized risk assessment tool that combines tools which can be easily used and implemented in the clinical workflow by doctors and qualified medical staff. The hypothesis was that the structured assessment and risk-grouping is predictive of short-term surgical quality reflected by complications and overall survival. METHODS: The Protego Maxima Trial was a prospective cohort analysis of patients undergoing major surgery (visceral, thoracic, urology, vascular and gynecologic surgeries) as key inclusion criterion and the absence of an acute or acute on chronically decompensated pulmo-cardiovascular decompensation. Patients were risk-scored with the software (The Prehab App) that includes a battery of evidence-based risk assessment tools that allow a structured risk assessment. The data were grouped to predefined high and low risk groups and aggregate and individual scores. The primary outcome was to validate the predictive value of the RAI score and the TUG for overall survival in the high and low risk groups. Secondary outcomes were surgical outcomes at 90-days after surgery (overall survival, Clavien-Dindo (CD) 1-5 (all complications), and CD 3-5 (major complications)). The study was carried out in accordance with the DIN ISO 14,155, and the medical device regulation (MDR) at Frankfurt University Hospital between March 2022 and January 2023. RESULTS: In total 267 patients were included in the intention to treat analysis. The mean age was 62.1 ± 12.4 years. Patients with a RAI score > 25 and/or a timed up and go (TUG) > 8 s had a higher risk for mortality at 90 days after surgery. The low-risk group predicted beneficial outcome and the high-risk group predicted adverse outcome in the ROC analysis (Area Under the Curve Receiver Operator Characteristics: AUROC > 0.800; p = 0.01). Risk groups (high vs. low) showed significant differences for 90-day survival (99.4% vs. 95.5%; p = 0.04) and major complications (16.4% vs. 32.4%; p < 0.001). CONCLUSION: The proof-of-concept trial showed that a risk assessment with 'The Prehab App' may be viable to estimate the preoperative risk for mortality and major complications before major surgeries. The overall performance in this initial set of data indicated a certain reliability of the scoring and risk grouping, especially of the RAI score and the TUG. A larger data set will be required to proof the generalizability of the risk scoring to every subgroup and may be fostered by artificial intelligence approaches. TRIAL REGISTRATION: Ethics number: 2021-483-MDR/MPDG-zuständig monocentric; The Federal Institute for Pharmaceuticals and Medical Devices/BfArM, reference number: 94.1.04-5660-13655; Eudamed: CIV-21-07-0307311; German Clinical Trial Registry: DRKS 00026985.

Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

Influence of aberrant right hepatic artery on survival after pancreatic resection for ductal adenocarcinoma of the pancreatic head.

PURPOSE: The presence of an aberrant right hepatic artery (aRHA), arising from the superior mesenteric artery, is a common variant of the liver vascular anatomy. Considering that tumor spread occurs along vessels, the question arises, whether the presence of an aRHA influences the oncologic outcome after resection for cancer of the pancreatic head. METHODS: Patients with ductal adenocarcinoma of the pancreatic head, who underwent resection from 2011 to 2020 at the Frankfurt University Hospital, Germany, were analyzed retrospectively. Surgical records and computed tomography imaging were reviewed for the presence of aRHA. Overall and disease-free survival as well as hepatic recurrence were analyzed according to the presence of aRHA. RESULTS: aRHA was detected in 21 out of 145 patients (14.5%). The median overall survival was 26 months (95%CI 20.8-34.4), median disease-free survival was 12.1 months (95%CI 8.1-17.3). There was no significant difference in overall survival (26.1 versus 21.4 months, adjusted hazard ratio 1.31, 95%CI 0.7-2.46, p = 0.401) or disease-free survival (14.5 months versus 12 months, adjusted hazard ratio 0.98, 95%CI 0.57-1.71, p = 0.957) without and with aRHA. The hepatic recurrence rate was 24.4.% with conventional anatomy versus 30.8% with aRHA (adjusted odds ratio 1.36, 95%CI 0.3-5.38, p = 0.669). In the multivariable analysis, only lymphatic vessel invasion was an independent prognostic factor for hepatic recurrence. CONCLUSIONS: The presence of an aRHA does not seem to influence the long-term survival and hepatic recurrence after resection for ductal adenocarcinoma of the pancreatic head.

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.

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.

Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma.

AIMS: The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions. METHODS AND RESULTS: All patients treated with surgically resected iCCA at Frankfurt University Hospital between December 2005 and March 2023 were retrospectively analysed. Histomorphological features of SD- and LD-iCCA were evaluated by an expert hepatobiliary pathologist. Tissue samples suspicious for subtype heterogeneity were further investigated. Immunohistochemistry for N-cadherin, S100P, MUC5AC, MUC6, TFF1 and AGR2 and mutational profiling with the Illumina TruSight Oncology 500 (TSO500) assay were performed separately for the SD- and LD-iCCA regions. Of 129 patients with surgically resected iCCA, features of either SD- or LD-iCCA were present in 67.4% (n = 87) and 24.8% of the patients (n = 32), respectively; 7.8% (n = 10) had histomorphological features of both SD- and LD-iCCA, seven patients (5.4%) of which had sufficient formalin-fixed, paraffin-embedded tissue for further analysis. Heterogeneity of both subtypes could be confirmed with immunohistochemistry. In five of seven (71.4%) patients, molecular profiling revealed intratumoural differences in genetic alterations between the SD- and LD-iCCA region. In one patient, a BRAF mutation (p.V600E) was found in the SD-iCCA but not in the LD-iCCA region of the tumour. CONCLUSIONS: A marked portion of patients with iCCA exhibits both SD- and LD-iCCA in different tumour regions. In case of the presence of histopathological heterogeneity, mutational profiling should be considered to avoid missing therapeutically relevant genetic alterations.

Pan-European survey on current treatment strategies in patients with upfront resectable colorectal liver metastases.

BACKGROUND: There is a lack of consensus on the definition of upfront resectability and use of perioperative systemic therapy for colorectal liver metastases (CRLM). This survey aimed to summarize the current treatment strategies for upfront resectable CRLM throughout Europe. METHODS: A survey was sent to all members of the European-African Hepato-Pancreato-Biliary Association to gain insight into the current views on resectability and the use of systemic therapy for upfront resectable CRLM. RESULTS: The survey was completed by 87 surgeons from 24 countries. The resectability of CRLM is mostly based on the volume of the future liver remnant, while considering tumor biology. Thermal ablation was considered as an acceptable adjunct to resection in parenchymal-sparing CRLM surgery by 77 % of the respondents. A total of 40.2 % of the respondents preferred standard perioperative systemic therapy and 24.1 % preferred standard upfront local treatment. CONCLUSION: Among the participating European hepato-pancreato-biliary surgeons, there is a high degree of consensus on the definition of CRLM resectability. However, there is much variety in the use of adjunctive thermal ablation. Major variations persist in the use of perioperative systemic therapy in cases of upfront resectable CRLM, stressing the need for further evidence and a consensus.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats.

BACKGROUND: This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). METHODS: Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. RESULTS: In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DISCUSSION: This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

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.

[Epidemiology and diagnostics of mesenteric ischemia]. / Epidemiologie und Diagnostik der mesenterialen Ischämie.

BACKGROUND: Mesenteric ischemia is a life-threatening condition with a complex etiology and diagnostics. OBJECTIVE: Etiology, incidence, symptoms, and diagnostics of acute and chronic mesenteric ischemia. MATERIAL AND METHODS: Literature search via PubMed with a focus on studies on the epidemiology and diagnostics of mesenteric ischemia and analysis of existing international guidelines. RESULTS: The incidence of acute mesenteric ischemia is given as 0.63-12.9 per 100,000 people per year. There are no sufficiently reliable figures for chronic mesenteric ischemia, but an incidence of up to 3 per 100,000 inhabitants per year is generally assumed. The three-phase computed tomography has the highest diagnostic specificity and sensitivity. CONCLUSION: In the presence of risk factors acute and chronic mesenteric ischemia should be considered as differential diagnoses in the presence of abdominal pain using three-phase computed tomography.

Active Autophagy Is Associated with Favorable Outcome in Patients with Surgically Resected Cholangiocarcinoma.

Data on the impact of autophagy in primary cholangiocarcinoma (CCA) remain scarce. Here, we therefore investigated the role of active autophagy and its impact on survival in CCA patients. All CCA patients who underwent surgical resection with curative intent between 08/2005 and 12/2021 at University Hospital Frankfurt were evaluated. Autophagic key proteins were studied by immunohistochemistry. iCCA processed for gene expression profiling of immune-exhaustion gene sets was used for an autophagy approach in silico. Active autophagy was present in 23.3% of the 172 CCA patients. Kaplan-Meier curves revealed median OS of 68.4 months (95% CI = 46.9-89.9 months) and 32.7 months (95% CI = 23.6-41.8 months) for active and non-active autophagy, respectively (p ≤ 0.001). In multivariate analysis, absence of active autophagy (HR = 2, 95% CI = 1.1-3.5, p = 0.015) was an independent risk factor for OS. Differential-expression profiling revealed significantly upregulated histone deacetylases (HDAC) mRNA in patients showing non-active autophagy. In line with this, pan-acetylated lysine was significantly more prominent in CCA patients with ongoing autophagy (p = 0.005). Our findings strengthen the role of active autophagy as a prognostically relevant marker and a potential therapeutic target.

Epidemiology of liver transplantation and post-LT complications in Germany: nationwide study (2005-2018).

BACKGROUND: To date, liver transplantation (LT) is the only curative treatment for cirrhosis and early-diagnosed progressive acute liver failure (ALF). However, LT results in morbidities and mortality even post-LT. Different comorbidities may follow and further increase mortality and morbidity. In this study, we investigated the outcomes and their trends over a period of 14 years among hospitalized patients evaluated for LT, transplant and post-LT in Germany. METHODS: This German nationwide study investigated the number of admissions of patients hospitalized for evaluation of LT and post-LT on related comorbidities and complications between 2005 and 2018 based on the DRG system with ICD-10/OPS codes. 14 745 patients were put on the LT waiting list and 12 836 underwent LT during the observational period. RESULTS: The LT number decreased by 2.3% over time, while the waiting list mortality rate increased by 5%. By contrast, the in-hospital mortality rate decreased by 3%, especially in ALF patients (decrease of 16%). Interestingly, admissions of post-LT patients for complications almost doubled, driven mainly by complications of immunosuppression (tripled). Importantly, post-LT patients with acute kidney injury (20.2%) and biliodigestive anastomosis (18.4%) showed the highest in-hospital mortality rate of all complications. CONCLUSION: In conclusion, the decrease in LT leads most probably to the increased in-hospital mortality of patients on the waiting list. Interestingly, in-hospital mortality decreased in LT patients. Post-LT comorbidities requiring hospitalization increased in the observational period and management of patients post-LT with AKI or biliodigestive anastomosis should be addressed.

The Diagnosis and Treatment of Ampullary Carcinoma.

BACKGROUND: Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform treatment recommendations are lacking both for the adjuvant situation and for palliative care. METHODS: A selective literature search was carried out in PubMed in order to identify the most informative publications concerning the epidemiology, clinico-pathological background, and surgical and medical treatment of this condition. RESULTS: Ampullary carcinoma has an incidence of 0.5 to 0.9 per 100 000 persons and a poor prognosis, with a 5-year survival rate of 41% to 45% for locally confined and 4% to 7% for metastatic disease. Most such tumors are of an intestinal or a pan - creaticobiliary immunohistochemical subtype; the latter has a worse prognosis (median survival, 72-80 vs. 33-41 months). Targeted treatment is not yet available for either subtype, nor is there enough scientific evidence available for the formulation of specific therapeutic recommendations in either the adjuvant or the palliative situation. The treatment of choice for ampullary carcinoma is radical oncological resection of the head of the pancreas with systematic lymphadenectomy. Five-year overall survival is between 10% and 75% depending on the stage. No definitive recommendation for adjuvant therapy can be given. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct. CONCLUSION: The current state of the evidence on the treatment of ampullary carcinoma is poor. Therapeutic decisions should be discussed in an interdisciplinary tumor board and should, in our opinion, take the histological subtype into account.

Chemotherapy and Targeted Therapy Strategies in Patients with Unresectable or Borderline Resectable Metastatic Colorectal Cancer: Evidence for a Lack of Focus on Resection Rates.

BACKGROUND AND AIMS: Chemotherapy (CTx) with targeted therapy (TT) have increased the overall response rate (ORR) and improved survival in unresectable or borderline resectable metastatic colorectal cancer (mCRC). However, the resection rate is an endpoint with often suboptimal expert involvement. The aim was to investigate whether the improvements in ORR have translated to improved resection rates (RR). STUDY DESIGN: A systematic literature search was performed using the PICO process. STATISTICAL ANALYSIS: Odds ratios, and 95% confidence intervals (OR, 95% CI) were analyzed for ORR and RR using dichotomous values with the Mantel-Haenszel method. Progression-free survival (PFS) and overall survival (OS) were analyzed using the inverse-variance method and displayed as hazard ratios and 95% confidence intervals (HR, 95% CI). RESULTS: The literature search returned 469 records. Sixteen articles with 5724 patients were selected for analysis. The qualitative analysis revealed low and moderate risk of bias endpoints. Higher ORR was observed with CTx + TT versus CTx only (OR: 0.62 [95% CI 0.45; 0.82], p = 0.002) and with triplet CTx + TT versus doublet CTx + TT (OR: 0.61 [95% CI 0.46; 0.81], p < 0.001). PFS and OS were improved by use of TT (HR: 0.68-0.84; p < 0.001 to 0.04). The overall RR was low (< 15%) and did not improve in the same way as the other endpoints. CONCLUSION: The ORR and survival rates in unresectable and borderline resectable mCRC were improved by modern CTx and TT that did not translate into higher RR, mostly due to the lack of expert involvement.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

A toolbox for a structured risk-based prehabilitation program in major surgical oncology.

Prehabilitation is a multimodal concept to improve functional capability prior to surgery, so that the patients' resilience is strengthened to withstand any peri- and postoperative comorbidity. It covers physical activities, nutrition, and psychosocial wellbeing. The literature is heterogeneous in outcomes and definitions. In this scoping review, class 1 and 2 evidence was included to identify seven main aspects of prehabilitation for the treatment pathway: (i) risk assessment, (ii) FITT (frequency, interventions, time, type of exercise) principles of prehabilitation exercise, (iii) outcome measures, (iv) nutrition, (v) patient blood management, (vi) mental wellbeing, and (vii) economic potential. Recommendations include the risk of tumor progression due to delay of surgery. Patients undergoing prehabilitation should perceive risk assessment by structured, quantifiable, and validated tools like Risk Analysis Index, Charlson Comorbidity Index (CCI), American Society of Anesthesiology Score, or Eastern Co-operative Oncology Group scoring. Assessments should be repeated to quantify its effects. The most common types of exercise include breathing exercises and moderate- to high-intensity interval protocols. The program should have a duration of 3-6 weeks with 3-4 exercises per week that take 30-60 min. The 6-Minute Walking Testing is a valid and resource-saving tool to assess changes in aerobic capacity. Long-term assessment should include standardized outcome measurements (overall survival, 90-day survival, Dindo-Clavien/CCI®) to monitor the potential of up to 50% less morbidity. Finally, individual cost-revenue assessment can help assess health economics, confirming the hypothetic saving of $8 for treatment for $1 spent for prehabilitation. These recommendations should serve as a toolbox to generate hypotheses, discussion, and systematic approaches to develop clinical prehabilitation standards.