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Background: Failure to rescue (FTR) is defined as the inability to prevent death after the development of a complication. FTR is a parameter in evaluating multidisciplinary postoperative complication management. The aim of this study was to evaluate FTR rates after major liver resection for perihilar cholangiocarcinoma (pCCA) and analyze factors associated with FTR., Patients and Method: Patients who underwent major liver resection for pCCA at 27 centers were included. FTR was defined as the presence of a Dindo grade III or higher complication followed by death within 90 days after surgery. Liver failure ISGLS grade B/C were scored. Multivariable logistic analysis was performed to identify predictors of FTR and reported using odds ratio and 95% confidence intervals., Results: In the 2186 included patients, major morbidity rate was 49%, 90-day mortality rate 13%, and FTR occurred in 24% of patients with a grade III or higher complication. Across centers, major complication rate varied from 19 to 87%, 90-day mortality rate from 5 to 33%, and FTR ranged from 11 to 50% across hospitals. Age [1.04 (1.02-1.05) years], ASA 3 or 4 [1.40 (1.01-1.95)], jaundice at presentation [1.79 (1.16-2.76)], right-sided resection [1.45 (1.06-1.98)], and annual hospital volume < 6 [1.44 (1.07-1.94)] were positively associated with FTR. When liver failure is included, the odds ratio for FTR is 9.58 (6.76-13.68)., Conclusion: FTR occurred in 24% of patients after resection for pCCA. Liver failure was associated with a nine-fold increase of FTR and hospital volume below six was also associated with an increased risk of FTR., Competing Interests: Disclosures: Ulf Neumann presented for Astra Zeneca, Roche AG, Merck AG, and Dr Falk GMBH, BMS. No other conflicts of interest are present. Data available upon reasonable request., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer and liver resection with complete tumor removal is the best treatment option for these patients. This study examines the predictive ability of three-dimensional lung volumetry (3DLV) based on preoperative computerized tomography (CT), to predict postoperative pulmonary complications in patients undergoing major liver resection for CRLM. Patients undergoing major curative liver resection for CRLM between 2010 and 2021 with a preoperative CT scan of the thorax within 6 weeks of surgery, were included. Total lung volume (TLV) was calculated using volumetry software 3D-Slicer version 4.11.20210226 including Chest Imaging Platform extension ( http://www.slicer.org ). The area under the curve (AUC) of a receiver-operating characteristic analysis was used to define a cut-off value of TLV, for predicting the occurrence of postoperative respiratory complications. Differences between patients with TLV below and above the cut-off were examined with Chi-square or Fisher's exact test and Mann-Whitney U tests and logistic regression was used to determine independent risk factors for the development of respiratory complications. A total of 123 patients were included, of which 35 (29%) developed respiratory complications. A predictive ability of TLV regarding respiratory complications was shown (AUC 0.62, p = 0.036) and a cut-off value of 4500 cm 3 was defined. Patients with TLV < 4500 cm 3 were shown to suffer from significantly higher rates of respiratory complications (44% vs. 21%, p = 0.007) compared to the rest. Logistic regression analysis identified TLV < 4500 cm 3 as an independent predictor for the occurrence of respiratory complications (odds ratio 3.777, 95% confidence intervals 1.488-9.588, p = 0.005). Preoperative 3DLV is a viable technique for prediction of postoperative pulmonary complications in patients undergoing major liver resection for CRLM. More studies in larger cohorts are necessary to further evaluate this technique., (© 2024. The Author(s).)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: Body composition assessment, measured using single-slice computed tomography (CT) image at L3 level, and aerobic physical fitness, objectively measured using cardiopulmonary exercise testing (CPET), are each independently used for perioperative risk assessment. Sarcopenia (i.e. low skeletal muscle mass), myosteatosis [i.e. low skeletal muscle radiation attenuation (SM-RA)], and impaired objectively measured aerobic fitness (reduced oxygen uptake) have been associated with poor post-operative outcomes and survival in various cancer types. However, the association between CT body composition and physical fitness has not been explored. In this study, we assessed the association of CT body composition with selected CPET variables in patients undergoing hepatobiliary and pancreatic surgery., Methods: A pragmatic prospective cohort of 123 patients undergoing hepatobiliary and pancreatic surgery were recruited. All patients underwent preoperative CPET. Preoperative CT scans were analysed using a single-slice CT image at L3 level to assess skeletal muscle mass, adipose tissue mass, and muscle radiation attenuation. Multivariate linear regression was used to test the association between CPET variables and body composition. Main outcomes were oxygen uptake at anaerobic threshold ( V ̇ O 2 at AT), oxygen uptake at peak exercise ( V ̇ O 2 peak), skeletal muscle mass, and SM-RA., Results: Of 123 patients recruited [77 men (63%), median age 66.9 ± 11.7, median body mass index 27.3 ± 5.2], 113 patients had good-quality abdominal CT scans available and were included. Of the CT body composition variables, SM-RA had the strongest correlation with V ̇ O 2 peak (r = 0.57, P < 0.001) and V ̇ O 2 at AT (r = 0.45, P < 0.001) while skeletal muscle mass was only weakly associated with V ̇ O 2 peak (r = 0.24, P < 0.010). In the multivariate analysis, only SM-RA was associated with V ̇ O 2 peak (B = 0.25, 95% CI 0.15-0.34, P < 0.001, R 2  = 0.42) and V ̇ O 2 at AT (B = 0.13, 95% CI 0.06-0.18, P < 0.001, R 2  = 0.26)., Conclusions: There is a positive association between preoperative CT SM-RA and preoperative physical fitness ( V ̇ O 2 at AT and at peak). This study demonstrates that myosteatosis, and not sarcopenia, is associated with reduced aerobic physical fitness. Combining both myosteatosis and physical fitness variables may provide additive risk stratification accuracy and guide interventions during the perioperative period., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Surgical resection is the only potentially curative treatment for patients with cholangiocarcinoma. For both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA), 5-year overall survival of about 30% has been reported in large series. This review addresses several challenges in surgical management of cholangiocarcinoma. The first challenge is diagnosis: a biopsy is typically avoided because of the risk of seeding metastases and the low yield of a brush of the bile duct. However, about 15% of patients with suspected pCCA are found to have a benign diagnosis after resection. The second challenge is staging; even with the best preoperative imaging, a substantial percentage of patients has occult metastatic disease detected at staging laparoscopy or early recurrence after resection. The third challenge is an adequate volume and function of the future liver remnant, which may require preoperative biliary drainage and portal vein embolization. The fourth challenge is a complete resection: a positive bile duct margin is not uncommon because the microscopic biliary extent of disease may be more extensive than perceived on imaging. The fifth challenge is the high post-operative mortality that has decreased in very high volume Asian centres, but remains about 10% in many Western referral centres. The sixth challenge is that even after a complete resection most patients develop recurrent disease. Recent randomized controlled trials found conflicting results regarding the benefit of adjuvant chemotherapy. The final challenge is to determine which patients with cholangiocarcinoma should undergo liver transplantation rather than resection., (© 2019 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Routine prophylactic abdominal drainage after hepatic surgery is still being debated, as it may be unnecessary, possibly harmful, and uncomfortable for patients. This study evaluated the safety of a no-drain policy after liver resection within an Enhanced Recovery after Surgery (ERAS) programme., Methods: All hepatectomies performed without prophylactic drainage during 2005-2014 were included. Primary end points were resection-surface-related (RSR) morbidity, defined as the presence of postoperative biloma, hemorrhage or abscess, and reinterventions. Secondary end points were length of stay, total postoperative morbidity, the composite end point of liver surgery-specific complications, readmissions, and 90-day mortality. Uni- and multivariate analyses were performed to identify independent risk factors for RSR morbidity. A systematic search was performed to compare the results of this study to literature., Results: A total of 538 resections were included in the study. The RSR complication and reintervention rate was 15 and 12%, respectively. Major liver resection (≥3 segments) was an independent risk factor for the development of RSR morbidity (OR 3.01, 95% CI 1.61-5.62; p = 0.001) and need for RSR reintervention (OR 3.02, 95% CI 1.59-5.73; p = 0.001)., Conclusion: RSR morbidity, mortality, and reintervention rates after liver surgery without prophylactic drainage in patients, treated within an ERAS programme, were comparable to previously published data. A no-drain policy after partial hepatectomy seems safe and feasible., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Postoperative liver failure (PLF) is a dreaded complication after partial hepatectomy. The peak bilirubin criterion (>7.0 mg/dL or ≥120 μmol/L) is used to define PLF. This study aimed to validate the peak bilirubin criterion as postoperative risk indicator for 90-day liver-related mortality., Methods: Characteristics of 956 consecutive patients who underwent partial hepatectomy at the Maastricht University Medical Centre or Royal Free London between 2005 and 2012 were analyzed by uni- and multivariable analyses with odds ratios (OR) and 95% confidence intervals (95%CI)., Results: Thirty-five patients (3.7%) met the postoperative peak bilirubin criterion at median day 19 with a median bilirubin level of 183 [121-588] μmol/L. Sensitivity and specificity for liver-related mortality after major hepatectomy were 41.2% and 94.6%, respectively. The positive predictive value was 22.6%. Predictors of liver-related mortality were the peak bilirubin criterion (p < 0.001, OR = 15.9 [95%CI 5.2-48.7]), moderate-severe steatosis and fibrosis (p = 0.013, OR = 8.5 [95%CI 1.6-46.6]), ASA 3-4 (p = 0.047, OR = 3.0 [95%CI 1.0-8.8]) and age (p = 0.044, OR = 1.1 [95%CI 1.0-1.1])., Conclusion: The peak bilirubin criterion has a low sensitivity and positive predictive value for 90-day liver-related mortality after major hepatectomy., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background Data: Hepatic sinusoidal dilatation (SD) is a histopathological entity that occurs in up to 75% of patients undergoing oxaliplatin-based chemotherapy for colorectal liver metastases (CRLM)., Objective: To study the influence of SD on outcome after partial hepatectomy in patients with CRLM., Methods: Medline, Embase, CENTRAL, LILACS and CINAHL were searched for studies published between 01.01.2004 and 09.06.2015 with keywords: "sinusoidal obstruction syndrome", "hepatic veno-occlusive disease", and "Stuart-Bras syndrome". Studies comprising adults who underwent partial hepatectomy for CRLM with grading of SD and registration of postoperative morbidity and/or mortality were included. Risk of bias and quality of studies were evaluated with the Quality In Prognosis Studies Instrument (QUIPS) and modified GRADE framework., Results: Search strategies produced 2007 hits from which 23 and 13 articles were extracted for qualitative and quantitative analyses, respectively. Meta-analysis on the influence of SD grade 2-3 vs. SD grade 0-1 on postoperative overall morbidity showed an odds ratio (OR) of 1.26 [95% CI 0.74, 2.15](p = 0.40), an OR of 1.03 [0.15, 6.89](p = 0.98) for liver failure, an OR of 1.21 [0.23, 6.35](p = 0.82) for overall mortality, and an OR of 3.52 [0.31, 39.91](p = 0.31) for liver-related morbidity. QUIPS showed a low to high risk of bias for studies, and GRADE showed very low quality of evidence per outcome., Conclusions: No significant effect of SD grade 2-3 on short-term outcome after partial hepatectomy was found. However, the data on which this conclusion was based were not very robust and therefore no solid conclusions could be drawn., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The impact of body composition on outcomes after surgery for colorectal liver metastases (CRLM) remains unclear. The aim of the present study was to determine the influence of sarcopenia, obesity and sarcopenic obesity on morbidity, disease-free (DFS) and overall survival (OS)., Method: Between 2005 and 2012, all patients undergoing a partial liver resection for CRLM in the Maastricht University Medical Centre, and who underwent computed tomography (CT) imaging within 3 months before liver surgery, were included. Body composition was primarily based on pre-operative CT measurements. Sarcopenia was based on total muscle area at the level of the third lumbar vertebra and predefined body mass index (BMI)- and gender-specific cut-off values for sarcopenia were used. Body fat percentages were calculated and the top 40% for men and women were considered obese., Results: Of the 171 included patients undergoing liver surgery for CRLM, 80 (46.8%) patients were sarcopenic, 69 (40.4%) obese and 49 (28.7%) sarcopenic obese. The presence of sarcopenia, obesity or sarcopenic obesity did not affect the complication rates. However, readmission rates were significantly increased in patients with (sarcopenic) obesity (P < 0.05). Surprisingly, obesity seemed to prolong OS (P = 0.021) and was identified as an independent predictor [hazard ratio (HR):0.58 and P = 0.046] for better OS. Sarcopenia and sarcopenic obesity did not affect DFS or OS., Conclusion: Sarcopenia, obesity and sarcopenic obesity did not worsen DFS, OS and complication rates after a partial liver resection for CRLM., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Currently, resection criteria for colorectal cancer liver metastases (CRCLM) are only limited by remnant liver function. Morbidity and survival after a partial hepatectomy with limited or extended indication criteria were compared., Methods/design: Between 1991 and 2010, patients undergoing a liver resection for CRCLM with limited (n = 169) or extended indication criteria (n = 129) were retrospectively identified in a prospectively collected single-centre database. Limited indication criteria were defined as less than three unilateral, not centrally located liver metastases in the absence of extra hepatic metastases. The extended criteria were only limited by predicted remnant liver volume and patients fitness. Data on co-morbidity, resection margin, short- and long-term morbidity, disease-free (DFS) and overall survival were compared., Results: Patients with limited indications had less major complications (19.5% vs. 33.1%, P < 0.01), longer overall survival of 68.8 months [confidence interval (CI) 46.5-91.1] vs. 41.4 months (CI 33.4-49.0, P ≤ 0.001) and longer median DFS of 22.0 months [confidence interval (CI) 15.8-28.2] vs 10.2 months (CI 8.4-11.9, P < 0.001) compared with the extended indication group. Cure rates, defined as 10-year DFS, were 35.5% and 15.8%, respectively. Fewer patients in the extended indication group underwent an R0 resection (92.9% vs. 77.5%, P < 0.001). Only 17% of all R1 resected patients had recurrences at the transection plane., Conclusion: A partial hepatectomy for CRCLM with extended indications seems justified but is associated with higher complication rates, earlier recurrence and lower overall survival compared with limited indications. However, the median 5-year survival was substantial and a cure was achieved in 15.8% of patients., (© 2013 International Hepato-Pancreato-Biliary Association.)

Unlabelled: Postoperative infectious complications (PICs) are associated with significant morbidity after abdominal surgery. Using multivariate analysis of data from a prospective database, our study focused on the risk factors for PICs and the prevention of these complications after hepatectomy, with the goal of improving outcomes and reducing the length of hospital stays., Background: PICs following surgery are associated with significant morbidity, increase the length of hospital stays, and have a negative impact on long-term oncological outcome. The aim of this study was to determine the risk factors for PICs following partial hepatectomy and to validate these results with an external database., Methods: Between January 2006 and December 2009, 555 patients underwent elective partial hepatectomy. We prospectively collected and retrospectively analyzed demographic data, pathological variables, associated pathological conditions, and preoperative, intraoperative, and postoperative variables. The dependent variables studied were the occurrence of PICs, defined as development of one or more of the following conditions: pneumonia, sepsis, Central line-associated bloodstream infection, urinary tract infection, wound infection, and infected intra-abdominal fluid collection. PICs were devised in medical (PIMCs) and surgical (PISCs) complications. The incidence of PICs and validation of the predictive score were determined using an external prospective database of 342 patients., Results: The multivariate analysis identified three independent risk factors for PICs: the presence of a nasogastric tube (OR = 1.8), blood transfusion (OR = 1.9), and diabetes (OR = 2.4). The multivariate analysis identified only one independent risk factor for PISCs: an associated portal venous resection (OR = 5.5). The multivariate analysis identified four independent risk factors for PIMCs: presence of a biliary drainage (OR = 1.9), blood transfusion (OR = 2.1), diabetes (OR = 2.9), and presence of atrial fibrillation (OR = 3.6). According to the three predictive factors, the observed rates of PICs ranged from 18.8 % to 77.8 % and ranged from 24.2 % to 100 % in the external database. Predicted and observed risks of PICs were not statistically different., Conclusions: The correction of modifiable risk factors among the identified factors could reduce the incidence of PICs and, as a consequence, improve patient outcomes and reduce the length of hospital stays.

Background: Although the safety of liver surgery has improved enormously, hepatic surgery continues to face challenging complications. Therefore, improvements supported by evidence-based guidelines are still required. The conduct of randomized controlled trials in liver surgery using dichotomous outcomes requires a large sample size. The use of surrogate endpoints (SEPs) reduces sample size but SEPs should be validated before use., Aim: The aim of this review was to summarize the SEPs used in hepatic surgery related trials, their definitions and recapitulating the evidence validating their use., Method: A systematic computerized literature search in the biomedical database PubMed using the MeSH terms 'hepatectomy' or 'liver resection' or 'liver transection' was conducted. Search was limited to papers written in the English language and published between 1 January 2000 and 1 January 2010., Results: A total of 593 articles met the search terms and 49 articles were included in the final selection. Standard biochemical liver functions tests were the most frequently used SEP (32 of 49 the studies). The used definitions of SEPs varied greatly among the studies. Most studies referred to earlier published material to justify their choice of SEP. However, no validating studies were found., Conclusion: Many SEPs are used in liver surgery trials however there is little evidence validating them., (© 2012 International Hepato-Pancreato-Biliary Association.)

Objectives: Sarcopenia may negatively affect short-term outcomes after liver resection. The present study aimed to explore whether total functional liver volume (TFLV) is related to sarcopenia in patients undergoing partial liver resection., Methods: Analysis of total liver volume and tumour volume and measurements of muscle surface were performed in patients undergoing liver resection using OsiriX(®) and preoperative computed tomography. The ratio of TFLV to bodyweight was calculated as: [TFLV (ml)/bodyweight (g)]*100%. The L3 muscle index (cm(2) /m(2) ) was then calculated by normalizing muscle areas (at the third lumbar vertebral level) for height., Results: Of 40 patients, 27 (67.5%) were classified as sarcopenic. There was a significant correlation between the L3 skeletal muscle index and TFLV (r= 0.64, P < 0.001). Median TFLV was significantly lower in the sarcopenia group than in the non-sarcopenia group [1396 ml (range: 1129-2625 ml) and 1840 ml (range: 867-2404 ml), respectively; P < 0.05]. Median TFLV : bodyweight ratio was significantly lower in the sarcopenia group than in the non-sarcopenia group [2.0% (range: 1.4-2.5%) and 2.3% (range: 1.5-2.5%), respectively; P < 0.05]., Conclusions: Sarcopenic patients had a disproportionally small preoperative TFLV compared with non-sarcopenic patients undergoing liver resection. The preoperative hepatic physiologic reserve may therefore be smaller in sarcopenic patients., (© 2012 International Hepato-Pancreato-Biliary Association.)

Objectives: Both laparoscopic techniques and multimodal enhanced recovery programmes have been shown to improve recovery and reduce length of hospital stay. Interestingly, evidence-based care programmes are not widely implemented, whereas new, minimally invasive surgical procedures are often adopted with very little evidence to support their effectiveness. The present survey aimed to shed light on experiences of the adoption of both methods of optimizing recovery., Methods: An international, web-based, 18-question, electronic survey was composed in 2010. The survey was sent out to 673 hepatopancreatobiliary (HPB) centres worldwide in June 2010 to investigate international experiences with laparoscopic liver surgery, fast-track recovery programmes and surgery-related equipoise in open and laparoscopic techniques and to assess opinions on strategies for adopting laparoscopic liver surgery in HPB surgical practice., Results: A total of 507 centres responded (response rate: 75.3%), 161 of which finished the survey completely. All units reported performing open liver resections, 24.2% performed open living donor resections, 39.1% carried out orthotopic liver transplantations, 87.6% had experience with laparoscopic resections and 2.5% performed laparoscopic living donor resections. A median of 50 (range: 2-560) open and 9.5 (range: 1-80) laparoscopic liver resections per surgical unit were performed in 2009. Patients stayed in hospital for a median of 7 days (range: 2-15 days) after uncomplicated open liver resection and a median of 4 days (range: 1-10 days) after uncomplicated laparoscopic liver resection. Only 28.0% of centres reported having experience with fast-track programmes in liver surgery. The majority considered the instigation of a randomized controlled trial or a prospective register comparing the outcomes of open and laparoscopic techniques to be necessary., Conclusions: Worldwide dissemination of laparoscopic liver resection is substantial, although laparoscopic volumes are low in the majority of HPB centres. The adoption of enhanced recovery programmes in liver surgery is limited and should be given greater attention., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: The use of lLaparoscopic liver resection in terms of time to functional recovery, length of hospital stay (LOS), long-term abdominal wall hernias, costs and quality of life (QOL) has never been studied in a randomised controlled trial. Therefore, this is the subject of the international multicentre randomised controlled ORANGE II trial., Methods: Patients eligible for left lateral sectionectomy (LLS) of the liver will be recruited and randomised at the outpatient clinic. All randomised patients will undergo surgery in the setting of an ERAS programme. The experimental design produces two randomised arms (open and laparoscopic LLS) and a prospective registry. The prospective registry will be based on patients that cannot be randomised because of the explicit treatment preference of the patient or surgeon, or because of ineligibility (not meeting the in- and exclusion criteria) for randomisation in this trial. Therefore, all non-randomised patients undergoing LLS will be approached to participate in the prospective registry, thereby allowing acquisition of an uninterrupted prospective series of patients. The primary endpoint of the ORANGE II trial is time to functional recovery. Secondary endpoints are postoperative LOS, percentage readmission, (liver-specific) morbidity, QOL, body image and cosmetic result, hospital and societal costs over 1 year, and long-term incidence of incisional hernias. It will be assumed that in patients undergoing laparoscopic LLS, length of hospital stay can be reduced by two days. A sample size of 55 patients in each randomisation arm has been calculated to detect a 2-day reduction in LOS (90% power and α = 0.05 (two-tailed)).The ORANGE II trial is a multicenter randomised controlled trial that will provide evidence on the merits of laparoscopic surgery in patients undergoing LLS within an enhanced recovery ERAS programme., Trial Registration: ClinicalTrials.gov NCT00874224.

Objectives: The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM., Methods: Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day., Results: 24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed., Conclusion: Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery., Trial Registration: ClinicalTrials.gov NCT01099475.

Background: The objective of this study was to provide a systematic review on the introduction of laparoscopic liver surgery in the Netherlands, to investigate the initial experience with laparoscopic liver resections and to report on the current status of laparoscopic liver surgery in the Netherlands., Methods: A systematic literature search of laparoscopic liver resections in the Netherlands was conducted using PubMed/MEDLINE. Analysis of initial experience with laparoscopic liver surgery was performed by case-control comparison of patients undergoing laparoscopic left lateral sectionectomy matched with patients undergoing the open procedure in the Netherlands between the years 2000 and 2008. Furthermore, a nationwide survey was conducted in 2011 on the current status of laparoscopic liver surgery., Results: The systematic review revealed only 6 Dutch reports on actual laparoscopic liver surgery. Matched case-control comparison showed significant differences in the length of hospital stay, blood loss and operation time. Complications did not differ significantly between the two groups (26 vs. 21%). The 2011 survey showed that 21 centers in the Netherlands performed formal liver resections and that 49 (5% of total) laparoscopic liver resections were performed in 2010., Conclusion: The systematic review revealed that very few laparoscopic liver resections were performed in the Netherlands in the previous millennium. The matched case-control comparison of laparoscopic and open left lateral resection showed a reduction in hospital length of stay with comparable morbidity. The laparoscopic technique has been slowly adopted in the Netherlands, but its popularity seems to increase in recent years., (Copyright © 2012 S. Karger AG, Basel.)

Background: For patients who present with synchronous colorectal carcinoma and colorectal liver metastasis (CRLM), a reversed treatment sequence in which the CRLM are resected before the primary carcinoma has been proposed (liver-first approach). The aim of the present study was to assess the feasibility and outcome of this approach for synchronous CRLM., Methods: Between 2005 and 2010, 22 patients were planned to undergo the liver-first approach. Feasibility and outcomes were prospectively evaluated., Results: Of the 22 patients planned to undergo the liver-first strategy, the approach was completed in 18 patients (81.8%). The main reason for treatment failure was disease progression. Patients who completed treatment and patients who deviated from the protocol had a similar location of the primary tumour, as well as comparable size, number and distribution of CRLM (all P > 0.05). Post-operative morbidity and mortality were 27.3% and 0% following liver resection and 44.4% and 5.6% after colorectal surgery, respectively. On an intention-to-treat-basis, overall 3-year survival was 41.1%. However, 37.5% of patients who completed the treatment had developed recurrent disease at the time of the last follow-up., Conclusions: The liver-first approach is feasible in approximately four-fifths of patients and can be performed with peri-operative mortality and morbidity similar to the traditional treatment paradigm. Patients treated with this novel strategy derive a considerable overall-survival-benefit, although disease-recurrence-rates remain relatively high, necessitating a multidisciplinary approach., (© 2011 International Hepato-Pancreato-Biliary Association.)

Introduction: Arterial ammonia concentrations increase acutely during the anhepatic phase of a liver transplantation (LTx) and return to baseline within 1 h after reperfusion of a functioning liver graft. So far, this return to baseline has solely been attributed to hepatic ammonia clearance. No data exist on the potential contribution of altered renal ammonia handling to peritransplantation ammonia homoeostasis., Aim: The present study investigated the consequences of a hepatectomy and subsequent implantation of a partial liver graft on arterial ammonia concentrations and urinary ammonia excretion during a living donor liver transplantation (LDLTx)., Methods: Patients with end-stage liver disease undergoing LDLTx were selected. Samples of arterial blood and urine were taken before, during and 2 h after the anhepatic phase. Differences were tested using Wilcoxon's test. Results are given as median and range., Results: Eleven adult patients undergoing an LDLTx were included. Before hepatectomy, arterial ammonia concentrations were 89 μM (40-156 μM), increasing to 146 μM (102-229 μM) (P<0.001) during the anhepatic phase and returning to 79 μM (46-111 μM) (P<0.01) after reperfusion. Urinary ammonia excretion was initially 1.06 mmol/h (0.02-6.00 mmol/h), increasing to 3.81 mmol/h (0.32-12.55 mmol/h) (P=0.004) during the anhepatic phase and further increasing to 4.00 mmol/h (0.79-9.51 mmol/h) (P=0.013) after reperfusion., Conclusion: The kidney significantly increased urinary ammonia excretion during the anhepatic phase, which was sustained after reperfusion, contributing to the rapid decrease of ammonia concentrations. Accordingly, the plasma ammonia concentrations measured directly after LTx cannot simply be used as a read-out of initial liver graft function., (© 2011 John Wiley & Sons A/S.)

Background & Aims: Aminotransferases are commonly used to determine the optimal duration of ischemic intervals during intermittent Pringle maneuver (IPM). However, they might not be responsive enough to detect small differences in hepatocellular damage. Liver fatty acid-binding protein (L-FABP) has been suggested as a more sensitive marker. This randomized trial aimed to compare hepatocellular injury reflected by L-FABP in patients undergoing liver resection with IPM using 15 or 30 min ischemic intervals., Methods: Twenty patients undergoing liver surgery were randomly assigned to IPM with 15 (15IPM) or 30 (30IPM) minutes ischemic intervals. Ten patients not requiring IPM (noIPM) served as controls. Primary endpoint was hepatocellular injury during liver surgery reflected by systemic L-FABP plasma levels. Between group comparisons were performed using area under the curve and repeated measures two-way ANOVA., Results: The IPM groups had similar characteristics. Aminotransferases did not differ significantly between 15IPM and 30IPM at any time point. L-FABP levels rose up to 1853±708 ng/ml in the 15IPM and 3662±1355 ng/ml in the 30IPM group after finishing liver transection and decreased rapidly thereafter. There were no significant differences between 15IPM and 30IPM in cumulative L-FABP level (p=0.378) or L-FABP level at any time point (p=0.149). Blood loss, remnant liver function and morbidity were comparable., Conclusions: IPM with 15 or 30 min ischemic intervals induced similar hepatocellular injury measured by the sensitive marker L-FABP. The present study confirms the results of earlier trials, suggesting that IPM with 30 min ischemic intervals may be used., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Post-operative liver failure following extensive resections for liver tumours is a rare but significant complication. The only effective treatment is liver transplantation (LT); however, there is a debate about its use given the high mortality compared with the outcomes of LT for chronic liver diseases. Cell therapy has emerged as a possible alternative to LT especially as endogenous hepatocyte proliferation is likely inhibited in the setting of prior chemo/radiotherapy. Both hepatocyte and stem cell transplantations have shown promising results in the experimental setting; however, there are few reports on their clinical application. This review identifies the potential stem cell sources in the body, and highlights the triggering factors that lead to their mobilization and integration in liver regeneration following major liver resections., (© 2011 John Wiley & Sons A/S.)

Background: Plasma interleukin-6 (IL-6) levels increase during liver resection. The source of this IL-6 is hitherto unclear. It has been demonstrated that the hepatosplanchnic area takes up IL-6 but the role of the gut and liver is unknown. The aim of the present study was to investigate the role of the gut and liver in IL-6 homeostasis during liver surgery., Methods: Before and after partial hepatectomy, IL-6 was measured in blood sampled from the radial artery, and the hepatic and portal vein. Blood flow was measured to assess IL-6 fluxes (flow times AV-differences) across the gut, liver and hepatosplanchnic area., Results: In 22 patients undergoing liver resection, IL-6 release from the gut after transection was 90.9 (30.1) ng/min (P < 0.001), whereas net IL-6 uptake by the liver equalled 83.4 (41.7) ng/min (P < 0.01). Overall hepatosplanchnic flux was 7.3 (43.5) ng/min after transection and did not differ significantly from zero. Overall hepatosplanchnic flux was 87.8 (41.5) ng/min in the major resection group and -59.8 (67.5) ng/min in the minor resection group (P < 0.05)., Discussion: The gut releases IL-6 and the liver takes up IL-6 before and after liver resection. The loss of IL-6 uptake as a result of a small functional remnant liver could lead to higher IL-6 levels after surgery., (© 2011 International Hepato-Pancreato-Biliary Association.)

Liver failure is a dreaded and often fatal complication that sometimes follows a partial hepatic resection. This article reviews the definition, incidence, pathogenesis, risk factors, risk assessment, prevention, clinical features and treatment of post-resectional liver failure (PLF). A systematic, computerized search was performed using key words related to 'partial hepatic resection' and 'liver failure' to review most relevant literature about PLF published in the last 20 years. The reported incidence of PLF ranges between 0.7 and 9.1%. An inadequate quantity or quality of residual liver mass are key events in its pathogenesis. Major risk factors are the presence of comorbid conditions, pre-existent liver disease and small remnant liver volume (RLV). It is essential to identify these risk factors during the pre-operative assessment that includes evaluation of liver volume, anatomy and function. Preventive measures should be applied whenever possible as curative treatment options for PLF are limited. These preventive measures intend to increase RLV and protect remnant liver function. Management principles focus on support of end-organ and liver function. Further research is needed to elucidate the exact pathogenesis of PLF and to develop and validate adequate treatment options.

Vreuls C P H, Van Den Broek M A, Winstanley A, Koek G H, Wisse E, Dejong C H, Olde Damink S W M, Bosman F T & Driessen A (2012) Histopathology 61, 314-318 Hepatic sinusoidal obstruction syndrome (SOS) reduces the effect of oxaliplatin in colorectal liver metastases Aims: Oxaliplatin is an important chemotherapeutic agent used to reduce hepatic colorectal metastases, resulting in tumour reduction and permitting surgical resection. This treatment has significant side effects, as oxaliplatin can induce sinusoidal obstruction syndrome (SOS) in the non-tumour-bearing liver, resulting in increased morbidity. We hypothesized that SOS might impede hepatic perfusion, thereby interfering with the tumour environment and attenuate the response to the chemotherapy. Methods and results: From the prospective database of the Maastricht University Medical Centre we collected 50 patients with hepatic colorectal carcinoma metastases. All patients received neo-adjuvant oxaliplatin followed by partial hepatectomy. Metastases and non-tumour-bearing liver were studied histopathologically. Thirty-two of 50 (64%) patients showed SOS lesions, classified as mild (26%) and moderate-severe (38%). The response to treatment, as expressed in the tumour regression grade (TRG), was grade 1 (10%); grade 2 (14%); grade 3 (28%); grade 4 (32%) and grade 5 (16%). Statistical analysis showed that a higher grade of SOS was associated with a higher grade of TRG ( P = 0.016). Conclusion: Developing SOS is associated with a lower tumour response to neo-adjuvant oxaliplatin treatment. Hepatic hypoperfusion due to sinusoidal obstruction syndrome might induce hepatic hypoxia, diminishing the response to chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The application of endobiliary self-expandable metallic stents (SEMS) is considered the palliative treatment of choice in patients with biliary obstruction in the setting of inoperable malignancies. In the presence of SEMS, however, radical surgery is the only curative option when the resectability status is revised in case of malignancies or for overcoming complications arising from their application in benign conditions that masquerade as inoperable tumours. The aim of our study was to report our surgical experience with patients who underwent an operation due to revision of the initial palliative approach, whilst they had already been treated with biliary SEMS exceeding the hilar bifurcation.Methods: Three patients with hilar cholangiocarcinoma that was considered inoperable and one patient with IgG4 autoimmune cholangio-pancreatopathy mimicking pancreatic cancer underwent radical resections in the presence of biliary SEMS.Results: After a detailed preoperative workup, two right trisectionectomies, one left extended hepatectomy and a radical extrahepatic biliary resection were performed. All cases demanded resection and reconstruction of the portal vein. R0 resection was achieved in all the malignant cases. Two patients required multiple biliodigestive anastomoses entailing three and seven bile ducts respectively. There was one perioperative death due to postoperative portal vein and hepatic artery thrombosis, whilst two patients developed grade III complications. At follow-up, one patient died at 13 months due to disease recurrence, whilst the remaining two are free of disease or symptoms at 21 and 12 months, respectively.Conclusions: Revising the initial palliative approach and operating in the setting of biliary metallic stents is extremely demanding and carries significant mortality and morbidity. Radical resection is the only option for offering cure in such complex cases, and this should only be attempted in advanced hepatopancreaticobiliary centres with active involvement in liver transplantation. [ABSTRACT FROM AUTHOR]

The gut is classically seen as the main source of circulating ammonia. However, the contribution of the intestines to systemic ammonia production may be limited by hepatic extraction of portal-derived ammonia. Recent data suggest that the kidney may be more important than the gut for systemic ammonia production. The aim of this study was to quantify the role of the kidney, intestines, and liver in interorgan ammonia trafficking in humans with normal liver function. In addition, we studied changes in interorgan nitrogen metabolism caused by major hepatectomy. From 21 patients undergoing surgery, blood was sampled from the portal, hepatic, and renal veins to assess intestinal, hepatic, and renal ammonia metabolism. In seven cases, blood sampling was repeated after major hepatectomy. At steady state during surgery, intestinal ammonia release was equaled by hepatic ammonia uptake, precluding significant systemic release of intestinal-derived ammonia. In contrast, the kidneys released ammonia to the systemic circulation. Major hepatectomy led to increased concentrations of ammonia and amino acids in the systemic circulation. However, transsplanchnic concentration gradients after major hepatectomy were similar to baseline values, indicating the rapid institution of a new metabolic equilibrium. In conclusion, since hepatic ammonia uptake exactly equals intestinal ammonia release, the splanchnic area, and hence the gut, probably does not contribute significantly to systemic ammonia release. After major hepatectomy, hepatic ammonia clearance is well preserved, probably related to higher circulating ammonia concentrations. [ABSTRACT FROM AUTHOR]