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Introduction There is an ongoing controversy surrounding portal vein embolization (PVE) regarding the short-term safety of PVE and long-term oncological benefit. This study aims to compare survival outcomes of patients subjected to major liver resection for colorectal liver metastases (CRLM) with or without PVE. Methods All consecutive patients who underwent major liver resection for CRLM in four high volume liver centres between January 2000 and December 2015 were included. Major liver resection was defined as resection of at least three Couinaud liver segments. To reduce selection bias, propensity score matching was performed for PVE and non-PVE patients with overall and disease-free survival as primary endpoints. For matching, all patients who underwent PVE followed by a major liver resection were selected. Patients were matched to patients who had undergone major liver resection without PVE. Results Of 745 patients undergoing major liver resection for CRLM, 53 patients (7%) underwent PVE before liver resection. In the overall cohorts, PVE patients had inferior DFS and a trend towards inferior OS. A total of 46 PVE patients were matched to 46 non-PVE patients to create comparable cohorts and between these two matched cohorts no differences in DFS (3-year DFS 16% vs 9%, p = 0.776) or OS (5-year OS 14% vs 14%, p = 0.866) were found. Conclusions This retrospective, matched analysis does not suggest a negative impact of PVE on long-term outcomes after liver resection in patients with CRLM. [ABSTRACT FROM AUTHOR]

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. Methods/Design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma. Trial registration: Netherlands Trial Register [NTR4243, 11 October 2013]. [ABSTRACT FROM AUTHOR]

Background: Biliary leakage after liver resection continues to be reported. Management of bile leakage has changed in recent years, with nowadays non-surgical procedures as the preferred treatment. Methods: Biliary leakage and management were assessed in 381 patients who underwent liver resection between January 2005 and April 2011. Results: The overall rate of biliary leakage after liver resection was 5.0%, with a higher incidence in patients who had undergone concomitant hepaticojejunostomy (HJ; 13.6 vs. 3.2%). Hospital stay (p = 0.047), major resections (p = 0.018), operation time (p = 0.011), and relaparotomy (p = 0.002) were risk factors for postoperative bile leakage. Multivariate analysis identified relaparotomy as an independent factor (OR 4.216, p = 0.034). Bile leakage in patients without HJ (n = 10) was managed in 6 patients by percutaneous transhepatic biliary drainage (PTD), and in 3 patients by endoscopic drainage. One patient was treated surgically. All patients with an HJ and postoperative bile leakage (n = 9) underwent PTD. Conclusion: The incidence of posthepatectomy biliary leakage has decreased over time, while PTD and endoscopic stenting are effective treatment modalities. PTD is the treatment of choice in bile leakage after resection combined with HJ. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Vascular occlusion can be applied during liver resection to reduce blood loss. Herein, we provide an update of the current evidence concerning vascular occlusion. Methods: A systematic literature search was conducted to review the effects of liver in- and outflow occlusion techniques during liver resection, focusing on blood loss and hepatic ischemia-reperfusion injury. Results: The Pringle maneuver (PM) is effective in controlling blood loss; however, there is no indication for routine vascular clamping during hepatic resection in uncomplicated patients. During complex resections and in patients with abnormal liver parenchyma, the intermittent PM is preferred over continuous clamping. Total hepatic vascular exclusion (THVE) is indicated only in resection of tumors involving the inferior caval vein or the caval hepatic junction. THVE can be applied with the preservation of caval vein flow. This mode of selective hepatic vascular exclusion results in less blood loss in combination with the PM. Conclusion: If clamping is necessary during complex resections or in abnormal liver parenchyma, intermittent PM is advised. THVE or selective hepatic vascular exclusion may be considered in tumors involving the inferior caval vein or the caval hepatic junction. There is no evidence supporting the use of ischemic preconditioning, maintenance of a low central venous pressure or of pharmacological interventions during liver resection. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hilar resection in combination with extended liver resections has resulted in a higher rate of R0 resections and increased survival in patients with hilar cholangiocarcinoma (HCCA). This aggressive surgical approach is, however, associated with high rates of operative morbidity and mortality, largely due to postresectional liver failure. We previously reported a series after resection of HCCA in which R0 resection rate was 59% with a mortality rate of 10%. In this study, we assessed mortality of extended liver resections after optimizing liver functional reserve and application of parenchyma-sparing techniques. Methods: From 2008 until June 2010, 41 consecutive patients underwent resection on the suspicion of HCCA. Preoperative workup included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. Modified right and left extended hemihepatectomies were performed preserving parts of segments 4 and 8, respectively, while pursuing complete excision of the tumor. Outcomes of resection were evaluated. Results: The majority of resections (78%) were performed for Bismuth type III-IV tumors. Preoperative biliary drainage was undertaken in 37 (90%) patients. Hilar resection in combination with liver resection was performed in 35 (85%) patients. Of these resections, 61% were modified extended resections including central liver resections. The R0 resection rate was 92%. Postoperative morbidity and mortality rates were 54 and 7%, respectively. Conclusion: Strategies to optimize liver function and to reduce removal of functional liver parenchyma were associated with a decrease in mortality (7%) while undertaking extended resection for HCCA with an R0 resection rate of 92%. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Portal vein ligation (PVL) and portal vein embolization (PVE) are used to induce hypertrophy of the future remnant liver before major liver resection. The aim of our study was to compare the hypertrophy response of the liver after PVL versus PVE in a rabbit model. Methods: Twenty rabbits were divided into an embolization group (n = 10) and a ligation group (n = 10). Both groups were divided in 2 subgroups of 5 rabbits that were humanely killed after days 7 and 14. The portal vein branches to the 3 cranial liver lobes (80% of the liver) were occluded. Regeneration of the caudal liver lobe was measured using volumetry based on computed tomography on days 3, 7, 10, and 14. Immunohistochemistry for Ki-67 and RAM11 was performed to quantify proliferating cells and macrophages. In addition, tissue tumor necrosis factor-α and interleukin-6 were assessed. Results: The caudal liver volume increased over time in both groups (P < .001), but this increase was greater after PVE than after PVL (P = .001) with a mean degree of hypertrophy of 15% ± 4% and 20% ± 2%, respectively. When comparing the groups on the separate time points, a difference was found on days 10 and 14 (P = .008 and P = .016, respectively). These data were confirmed by Ki-67 staining, which showed a greater number of proliferating hepatocytes on day 7 after embolization (P = .016). Cytokine analysis of liver tissue did not show significant differences between the ligation and embolization groups on days 7 and 14. Conclusion: PVE is superior to PVL in terms of the extent of the hypertrophy response in this rabbit model. [Copyright &y& Elsevier]

Background: (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) was used as a quantitative method to evaluate liver function. The aim of this study was to compare future remnant liver function assessed by (99m)Tc-mebrofenin hepatobiliary scintigraphy with future remnant liver volume in the prediction of liver failure after major liver resection.Methods: Computed tomography (CT) volumetry and (99m)Tc-mebrofenin hepatobiliary scintigraphy were performed prior to major resection in 55 high-risk patients, including 30 patients with parenchymal liver disease. Liver volume was expressed as percentage of total liver volume or as standardized future remnant liver volume. Receiver operating characteristic (ROC) curve analysis was performed to identify a cutoff value for future remnant liver function in predicting postoperative liver failure.Results: Postoperative liver failure occurred in nine patients. A liver function cutoff value of 2.69%/min/m(2) was calculated by ROC curve analysis. (99m)Tc-mebrofenin hepatobiliary scintigraphy demonstrated better sensitivity, specificity, and positive and negative predictive value compared to future remnant liver volume. Using 99mTc-mebrofenin hepatobiliary scintigraphy, one cutoff value suffices in both compromised and noncompromised patients.Conclusion: Preoperative (99m)Tc-mebrofenin hepatobiliary scintigraphy is a valuable technique to estimate the risk of postoperative liver failure. Especially in patients with uncertain quality of the liver parenchyma, (99m)Tc-mebrofenin HBS proved of more value than CT volumetry. [ABSTRACT FROM AUTHOR]

Aim: Although most partial liver resections are performed for malignant lesions, an increasing contingent of benign lesions is also considered for surgery. The aim was to assess post-operative morbidity and mortality after liver resection for benign hepatobiliary lesions in comparison with outcome after resection of malignant lesions. Methods: A total of 286 liver resections were undertaken between January 1992 and December 2004. After exclusion of resection for bile duct tumours or hepatocellular carcinoma, 205 partial liver resections were retrospectively analysed. Results: Patients with benign lesions comprised 34% of the group ( n=70). Benign lesions mainly consisted of focal nodular hyperplasia ( n=12; 17%) and liver haemangiomas (11; 15.7%). The malignant lesions consisted of colorectal tumour metastases ( n=121; 89%). Patients with benign lesions predominantly underwent minor liver resections (66 vs. 47%; P=0.013). The overall post-operative morbidity occurred in 31% (64/205). Major morbidity occurred in 16% (22/135) in the malignant group compared with 9% (6/70) in the benign group ( P=0.099). No differences were seen in major post-operative morbidity in the earlier period compared with the later period (14 vs. 14.3%, P=0.950). In multivariate analysis, only presence of comorbidity ( P=0.017), prolonged surgical procedure ( P=0.021) and surgical irradicality ( P=0.039) maintained significance as independent risk factors for major morbidity. Conclusion: Limited liver resections for the treatment of a wide range of benign hepatobiliary lesions are associated with low morbidity and no mortality. However, the indications must be assessed with care. The presence of comorbidity, prolonged surgical time and incomplete resections were associated with major morbidity. [ABSTRACT FROM AUTHOR]

Background/Aims: Portal vein embolization (PVE) has reached worldwide acceptance to increase future remnant liver (FRL) volume before undertaking major liver resection. The aim of this overview is to point out and discuss current controversies in the application of PVE. Methods: Review of literature pertaining to techniques of PVE, complications, tumor proliferation, timing of resection, and hypertrophy response after PVE. Results: Procedure-related complications after PVE include hematoma, hemobilia, overflow of embolization material, and thrombosis of portal vein branch(es) of the non-embolized lobe. Persistence of the embolized, atrophic lobe is usually not harmful. Embolization of the portal branches to segment 4 in addition to embolization of the right portal trunk is controversial and is advised only in selected cases. It remains undecided whether embolization of the portal venous system is more effective in inducing hypertrophy of the FRL than ligation of the portal vein. Accelerated tumor growth after PVE is a major concern and requires consideration of post-PVE chemotherapy. A waiting time of 3 weeks between PVE and liver resection is advised. Post-hepatectomy regeneration is not hampered after preoperative PVE. Conclusion: PVE is a useful preoperative intervention to increase volume and function of the FRL. Further progress awaits clarification of the mechanisms of the hypertrophy response induced by PVE in conjunction with new embolization materials and protective chemotherapy. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Control of bleeding from the transected liver basically consists of vascular inflow occlusion and control of hepatic venous backflow from the caval vein. Central venous pressure determines the pressure in the hepatic veins and is an extremely important factor in controlling blood loss through venous backflow. Vascular inflow occlusion (Pringle maneuver) involves clamping of the portal vein and the hepatic artery in the hepatic pedicle and gives rise to postischemic, reperfusion injury. Several strategies have been devised to reduce reperfusion injury (pharmacological interventions) or to increase ischemic tolerance of the liver (ischemic preconditioning). Intermittent clamping is recommended in complex liver resections or in patients with diseased livers. The combination of occlusion of vascular inflow and outflow of the liver results in total hepatic vascular exclusion (THVE) and is mainly used in tumors invading the caval vein. During THVE the liver can be cooled by hypothermic perfusion allowing for extended ischemia times. Selective THVE entails clamping of the main hepatic veins in their extrahepatic course, thus preserving caval flow. Safe liver surgery requires knowledge of the regular techniques of vascular occlusion for ‘on demand’ use when necessitated to reduce blood loss. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Liver resection is widely accepted as the only potentially curative treatment in malignant or benign hepatobiliary lesions. Although not frequent, biliary leakage is a postoperative complication which may have considerable consequences. The field of topical hemostatic agents is rapidly developing, with various products currently available. This article reviews the risk factors associated with biliary leakage and the methods used for testing or prevention of biliary leakage. A literature search was performed using key words related to experimental and clinical studies dealing with biliary leakage. Experimental studies assessed the potential biliostatic effect of different topical hemostatic agents after bile duct reconstruction. Clinical series show biliary leakage rates up to 12%. There is no evidence that flushing of the bile duct system after resection reduces the incidence of biliary leakage. Further controlled studies are needed to clarify the preventive effect of topical hemostatic agents on biliary leakage after liver resection. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hepatic venous outflow obstruction (HVOO) is a rare disorder that occurs predominantly due to a hypercoagulable state. The syndrome may result from hepatic vein obstruction, inferior vena cava obstruction or a combination of both and manifests with post-sinusoidal portal hypertension. The presentation may be fulminant with poor prognosis or as either acute, subacute or chronic forms with relatively better prognosis. Portosystemic shunt surgery (PSS) has thus far been the mainstay of treatment for HVOO. However, over the last decade, transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation have emerged as viable options. This review aims to evaluate the available treatment options and the current relevance of PSS for the management of HVOO. Methods: A literature review on investigations and treatment was performed using Medline and additional library searches. Results: Portosystemic shunts form the mainstay of treatment for patients with subacute presentation (preserved liver function) with medically intractable ascites or recurrent variceal hemorrhage. Excellent results with 5-year survival of more than 90% have been reported from specialized centers. The main limitation for PSS is the reported perioperative mortality of 10–20% and a declining technical expertise for such surgery. Liver transplantation with disease-specific 5-year survival between 50 and 95% is presently the treatment of choice for patients with fulminant presentation, end-stage liver disease (ESLD), unshuntable anatomy or decompensation after PSS. TIPS may be preferable for sick patients with acute presentation with isolated hepatic vein thrombosis or as a temporizing measure for those with ESLD awaiting transplantation. The drawback of TIPS is late shunt dysfunction that occurs in more than 50% of patients at 1 year. Conclusions: Due to rarity of the disorder there is a lack of trials comparing the different treatment modalities. Hence, the current treatment recommendations are based on retrospective studies. In a select group of HVOO patients (subacute presentation with preserved liver function), PSS remains the treatment of choice with excellent long-term results. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hepatocellular adenomas (HCA) may present with spontaneous haemorrhage and rupture. The aim of this study was to assess management in 22 patients treated for haemorrhage and/or rupture of HCA. Patients and methods: Between May 1990 and July 2005, 22 female patients were diagnosed with acute haemorrhage and/or rupture of lesions highly suspicious of HCA. Preoperative imaging diagnostics and pathologic specimens were reviewed. Results: Twelve haemodynamically stable and four unstable patients could be treated conservatively. One patient underwent acute partial liver resection, whereas four patients underwent laparotomy with initial packing of the liver. In one patient, selective embolisation of the left hepatic artery was performed. Fifteen patients eventually underwent resection after a mean time of 8 months after initial treatment. Six patients did not undergo resection and showed no complications or rebleeding after a mean follow-up of 24.6 months. Only in seven patients, histopathological examination showed HCA, and in one patient, HCA with focal nodular hyperplasia. Conclusion: HCA with haemorrhage and/or rupture does not necessarily require immediate liver resection. Conservative treatment is justified in stable patients. In case of an instable patient with or without hemoperitoneum, laparotomy with packing or selective embolisation can stop the bleeding. [ABSTRACT FROM AUTHOR]

This study analyzes the change in the management of biliary leakage after hepaticojejunostomy. Between 1993 and 2003 all patients (n = 1033) were studied with a hepaticojejunostomy as part of a pancreatoduodenectomy (n = 486), proximal bile duct resection (without liver resection) (n = 35), and biliodigestive bypass for malignant (n = 302) and benign (n = 210) disease. Biliary leakage was defined as the presence of bile-stained fluid (>50 mL) in the abdominal drain more than 24 hours after surgery, proven radiologically or at relaparotomy. The studied patients were divided into two equal periods to analyze the change in management. Overall, 24 of 1033 patients (2.3%) had biliary leakage. In multivariate analysis, a body mass index greater than 35 kg/m2 (P = .012), endoscopic biliary drainage (P = .044), and an anastomosis on the segmental bile ducts (P < .001) were independent predictors of leakage. Management in the first half of the study period (1993–1998) versus the second half (1999–2003) was maintenance of operatively placed drains (18% vs. 15%, respectively, P = 1.000), percutaneous transhepatic biliary drainage (18% vs. 69%, respectively, P = .012), surgical drainage (55% vs. 8%, respectively, P = .023), and re-hepaticojejunostomy (9% vs. 8%, respectively, P = 1.000). There was no mortality in the patients with biliary leakage. Leakage after a hepaticojejunostomy is a relatively rare complication without mortality and can safely be managed with percutaneous transhepatic biliary drainage. [Copyright &y& Elsevier]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents the author's views regarding the bloodless liver resection. The author notes that one of the most significant and prognostic factors determining postoperative mortality and morbidity after liver resection is the volume of operative blood loss. The methods to achieve bloodless liver resection have been the subject of symposia held in Amsterdam and in Athens.

Low central venous pressure (low-CVP) is the clinical standard for fluid therapy during major liver surgery. Although goal-directed fluid therapy (GDFT) has been associated with reduced morbidity and mortality in major abdominal surgery, concerns remain on blood loss when applying GDFT in liver surgery. This randomized trial compared outcomes of low-CVP and GDFT during major liver resections. In this surgeon- and patient-blinded RCT, patients undergoing major open liver resections (≥3 segments) were randomized between low-CVP (n = 20) or GDFT (n = 20). Primary outcome was intraoperative blood loss. Secondary outcomes included the quality of the surgical field (VAS scale 0 (worst)-100 (best)) and major morbidity (≥grade 3 Clavien-Dindo). During surgery, CVP was 3 ± 2 mmHg in the low-CVP group vs. 7 ± 3 mmHg in the GDFT group (P < 0.001). Blood loss (1425 vs. 1275 mL; P = 0.640) and the rate of major morbidity (40% vs. 50%, P = 0.751), did not differ between low-CVP and GDFT, respectively. The quality of the surgical field was comparable between groups (low-CVP 83% vs. GDFT 80%, P = 0.955). In major open liver resections, GDFT was not associated with differences in intraoperative blood loss, major morbidity or quality of the surgical field, compared to low-CVP. Larger RCTs are needed to confirm this finding. Registration number: NTR5821 (www.trialregister.nl). [ABSTRACT FROM AUTHOR]

It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging. Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging. [ABSTRACT FROM AUTHOR]

The value of open and minimally invasive liver resection for symptomatic solid benign liver tumours (BLT) such as hepatocellular adenoma, focal nodular hyperplasia and haemangioma is being debated. A systematic review on symptom relief, quality of life (QoL) and surgical outcome after both open and minimally invasive surgery for solid BLT is currently lacking. A systematic search in PubMed and EMBASE was performed according to the PRISMA guidelines (January 1985–April 2018). Articles reporting pre-and postoperative symptoms or QoL in patients undergoing open or minimally surgery for BLT were evaluated. Methodological quality was assessed using the MINORS tool. Forty-two studies were included with 4061 patients undergoing surgery for BLT, 3536 (87%) open and 525 (13%) laparoscopic resections. Randomized and propensity-matched studies were lacking. Symptoms were the indication for resection in 56% of the patients. After a weighted mean of 28.5 months follow-up after surgery, symptoms were relieved in 82% of symptomatic patients. Validated QoL tools were used in eight studies, of which two found significant better QoL scores following laparoscopic compared to open surgery. Resection of symptomatic BLT seems safe and relieves symptoms in the vast majority of selected patients. Comparative studies are needed before more firm conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Activation of sterile inflammation after hepatic ischemia/reperfusion (I/R) culminates in liver injury. The route to liver damage starts with mitochondrial oxidative stress and cell death during early reperfusion. The link between mitochondrial oxidative stress, damage-associate molecular pattern (DAMP) release, and sterile immune signaling is incompletely understood and lacks clinical validation. The aim of the study was to validate this relation in a clinical liver I/R cohort and to limit DAMP release using a mitochondria-targeted antioxidant in I/R-subjected mice. Plasma levels of the DAMPs high-mobility group box 1 (HMGB1), mitochondrial DNA, and nucleosomes were measured in 39 patients enrolled in an observational study who underwent a major liver resection with (N = 29) or without (N = 13) intraoperative liver ischemia. Circulating cytokine and neutrophil activation markers were also determined. In mice, the mitochondria-targeted antioxidant MitoQ was intravenously infused in an attempt to limit DAMP release, reduce sterile inflammation, and suppress I/R injury. In patients, HMGB1 was elevated following liver resection with I/R compared to liver resection without I/R. HMGB1 levels correlated positively with ischemia duration and peak post-operative transaminase (ALT) levels. There were no differences in mitochondrial DNA, nucleosome, or cytokine levels between the two groups. In mice, MitoQ neutralized hepatic oxidative stress and decreased HMGB1 release by ±50%. MitoQ suppressed transaminase release, hepatocellular necrosis, and cytokine production. Reconstituting disulfide HMGB1 during reperfusion reversed these protective effects. HMGB1 seems the most pertinent DAMP in clinical hepatic I/R injury. Neutralizing mitochondrial oxidative stress may limit DAMP release after hepatic I/R and reduce liver damage. • Hepatic ischemia/reperfusion leads to sterile inflammation and liver injury. • Liver surgery in patients triggers release of damage-associated molecular patterns. • Release of the DAMP HMGB1 is associated with clinical hepatic I/R injury. • The antioxidant MitoQ neutralizes mitochondrial oxidative stress after mouse liver I/R. • MitoQ reduces release of HMGB1 after mouse liver I/R. [ABSTRACT FROM AUTHOR]

Background Uncontrolled introduction of laparoscopic liver surgery (LLS) could compromise postoperative outcomes. A stepwise introduction of LLS combined with structured training is advised. This study aimed to evaluate the impact of such a stepwise introduction. Methods A retrospective, single-center case series assessing short term outcomes of all consecutive LLS in the period November 2006-January 2017. The technique was implemented in a stepwise fashion. To evaluate the impact of this stepwise approach combined with structured training, outcomes of LLS before and after a laparoscopic HPB fellowship were compared. Results A total of 135 laparoscopic resections were performed. Overall conversion rate was 4% (n = 5), clinically relevant complication rate 13% (n = 18) and mortality 0.7% (n = 1). A significant increase in patients with major LLS, multiple liver resections, previous abdominal surgery, malignancies and lesions located in posterior segments was observed after the fellowship as well as a decrease in the use of hand-assistance. Increasing complexity in the post fellowship period was reflected by an increase in operating times, but without comprising other surgical outcomes. Conclusion A stepwise introduction of LLS combined with structured training reduced the clinical impact of the learning curve, thereby confirming guideline recommendations. [ABSTRACT FROM AUTHOR]

Background Posthepatectomy liver failure (PHLF) is a threatening complication after liver surgery, especially in perihilar cholangiocarcinoma (PHC). This study aimed to assess the value of preoperative assessment of liver function using 99m Tc-mebrofenin hepatobiliary scintigraphy (HBS) to predict PHLF in comparison with liver volume in PHC patients. Methods All patients who underwent resection of suspected PHC in a single center between 2000 and 2015 were included in the analysis. PHLF was graded according to the ISGLS criteria with grade B/C considered clinically relevant. A cut-off value for the prediction of PHLF was calculated using the receiver operating characteristic curve (ROC) analysis. Results A total of 116 patients were included of which 27 (23%) suffered of PHLF. ROC values for the prediction of PHLF were 0.74 (0.63–0.86) for future liver remnant function and 0.63 (0.47–0.80) for volume. A cut-off for liver function was set at 8.5%/min, which resulted in a negative predictive value of 94% and positive predictive value of 41%. Conclusions Assessment of liver function with HBS had better predictive value for PHLF than liver volume in patients undergoing major liver resection for suspected PHC. The cut-off of 8.5%/min can help to select patients for portal vein embolization and might help to reduce postoperative liver failure. [ABSTRACT FROM AUTHOR]

Background: Major liver resection for perihilar cholangiocarcinoma (PHC) is associated with a 22% to 33% postoperative liver failure incidence. The aim of this study was analyze the predictive value of future liver remnant (FLR) volume for postoperative liver failure after resection for PHC and to develop a risk score to improve patient selection for portal vein embolization.Study Design: A consecutive series of 217 patients underwent major liver resection for PHC between 1997 and 2014 at 2 Western centers; FLR volumes were calculated with CT volumetry; other variables included jaundice at presentation, immediate preoperative bilirubin, and preoperative cholangitis. The FLR volume was categorized as <30%, 30% to 45%, or >45%. A risk score for postoperative liver failure (grade B/C according to the International Study Group of Liver Surgery criteria) was developed using multivariable logistic regression with 5 predefined variables.Results: Postoperative liver failure incidence was 24% and liver failure-related mortality was 12%. Risk factors for liver failure were FLR volume <30% (odds ratio 4.2; 95% CI 1.77 to 10.3) and FLR volume 30% to 45% (odds ratio 1.4; 95% CI 10.6 to 3.4). In addition, jaundice at presentation (odds ratio 3.1; 95% CI 1.1 to 9.0), immediate preoperative bilirubin >50 μmol/L (>2.9 mg/dL) (odds ratio 4.3; 95% CI 1.7 to 10.7), and preoperative cholangitis (odds ratio 3.4; 95% CI 1.6 to 7.4) were risk factors for liver failure. These variables were included in a risk score that showed good discrimination (area under the curve 0.79; 95% CI 0.72 to 0.86) and ranking patients in 3 risk sub-groups with predicted liver failure incidence of 4%, 14%, and 44%.Conclusions: The selection of patients for portal vein embolization using only liver volume is insufficient, considering the other predictors of liver failure in PHC patients. The proposed risk score can be used for selection of patients for portal vein embolization, for adequate patient counseling, and identification of other modifiable risk factors besides liver volume. [ABSTRACT FROM AUTHOR]

Background: Transaminase levels are usually measured as markers of hepatocellular injury following liver resection, but recent evidence was unclear on their clinical value. This study aimed to identify factors that determine peak postoperative transaminase levels and correlated transaminase levels to postoperative complications. Study design: All liver resections performed at a single center between 2006 and 2015 were included in the analysis. Multivariate analysis was used to identify factors that determine peak ALT and AST levels and postoperative morbidity and mortality. An ALT and AST cutoff for the prediction of mortality was determined using receiver operating characteristic curves analysis. Results: A total of 539 resections were included. Clavien-Dindo grade III or higher complications, intraoperative transfusion, and operative duration were identified as determinants of peak transaminases. A peak AST cut-off value for predicting mortality was defined at 828 U/L, with an area under the curve of 0.81 (0.73-0.89). The cut-off was an independent predictor of mortality (P < 0.01) along with (intraoperative) transfusion (P < 0.01), fifty-fifty criteria (P < 0.01), and age (P < 0.01). Conclusion: Postoperative transaminase levels are independent predictors of postoperative morbidity and mortality and therefore clinically relevant. Transaminase levels usually peak during the first 24 h after surgery and thus possess early prognostic power in terms of postoperative mortality. [ABSTRACT FROM AUTHOR]

Background: 99mTc-mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cutoff value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated. Methods: 163 patients who underwent major liver resection were included. Insufficient FRL-volume and/or FRL-function <2.7%/min/m² were indications for portal vein embolization (PVE). Non-PVE patients were compared with a historical cohort (n = 55). Primary endpoints were postoperative LF and LF related mortality. Secondary endpoint was preoperative identification of patients at risk for LF using the CT-volumetric methods. Results: 29/163 patients underwent PVE; 8/29 patients because of insufficient FRL-function despite sufficient FRL-volume. According to FRL-BWR and standardized liver volumetry, 16/29 and 11/29 patients, respectively, would not have undergone PVE. LF and LF related mortality were significantly reduced compared to the historical cohort. HBS appeared superior in the identification of patients with increased surgical risk compared to the CT-volumetric methods. Discussion: Implementation of HBS in the preoperative work-up led to a function oriented use of PVE and was associated with a significant decrease in postoperative LF and LF related mortality. [ABSTRACT FROM AUTHOR]

Introduction: Age itself is not considered a contraindication for high impact surgery. However, the aging process of the liver remains largely unknown. This study evaluates age-dependent changes in liver function using a quantitative liver function test. Methods: Between January 2005 and December 2014, 508 patients underwent 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) for the assessment of liver function. These included 203 patients with healthy livers (group A) and 57 patients with HCC and Child-Pugh A (group B). 99mTc-mebrofenin-uptake-rate of the whole liver corrected for body surface area (cMUR) was calculated for all patients. Linear regression analysis was performed to assess the relationship between age and cMUR. Results: The mean cMUR was 8.50 ± 2.05%/min/m2 and 6.94 ± 2.03%/min/m2 in group A and B, respectively. A negative linear correlation was found between patient's age and cMUR in group A, r = 0.244, p = 0.000. In group B, there was no correlation between age and cMUR, however, a trend in decline of liver function with age was noted. Conclusion: This study shows that liver function deteriorates with age. Since the regenerative capacity of the liver correlates with liver function, this finding should be taken into account when assessing surgical risk in patients considered for major liver resection. [ABSTRACT FROM AUTHOR]

Background Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE. Materials and methods We performed a systematic literature search in Medline and Pubmed, from 1993-June 2013, using search headings "PVE" and "portal vein ligation". Articles were included when meeting the selection criteria: experimental animal study on PVE or portal vein ligation and experiments described in 5 animals or more. Results Sixty-one articles were selected, describing six different animal models. Most articles reported experiments with rats, rabbits, and pigs. In rats, the increase in wet-weight ratio of the non-occluded liver or total liver weight is greatest in the first 7 d with values ranging from 75%-80.5% on day 7. The volume increase of FRL in the rabbit model is greatest in the first 7 d with values ranging from 33.6%-80% on day 7. In pigs, the largest gain in volume of the FRL was seen in the first 2 wk. Conclusions The choice of the model depends on the specific aim of the study. Evaluating the increase in liver volume and liver function after PVE, larger animals as the pig, rabbit, or the dog is useful because of the possibility to apply computed tomography volumetry. To evaluate mechanisms of regeneration after PVE, the rat model is useful, because of the variety of antibodies commercially available. [ABSTRACT FROM AUTHOR]

Background & Aims: 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) and the indocyanine green (ICG) clearance test are used for the assessment of hepatic function before and after liver surgery. The hepatic uptake of 99mTc-mebrofenin and ICG is considered similar to the uptake of organic anions such as bilirubin and bile acids. Little is known about hepatic uptake mechanisms of both compounds and recent evidence suggests that the hepatic transporters for ICG and 99mTc-mebrofenin are distinct. The aim of this study was to identify the specific human hepatic transporters of 99mTc-mebrofenin and ICG. Methods: The uptake of 99mTc-mebrofenin was investigated in cRNA-injected Xenopus laevis oocytes expressing human OATP1B1, OATP1B3, OATP2B1, or NTCP. Chinese hamster ovary (CHO) cells stably expressing OATP1B1, OATP1B3, OATP2B1, or NTCP were used as a mammalian expression system. ICG transport into CHO cells was additionally imaged with confocal microscopy. Results: We demonstrated that OATP1B1 and OATP1B3 are involved in the transport of 99mTc-mebrofenin. OATP1B1 showed an approximately 1.5-fold higher affinity for 99mTc-mebrofenin compared to OATP1B3. ICG is transported by OATP1B3 and NTCP. Conclusions: The transporter specificity of 99mTc-mebrofenin and ICG partially overlaps as both compounds are transported by OATP1B3. 99mTc-mebrofenin is also taken up by OATP1B1, whereas ICG is additionally transported by NTCP. [ABSTRACT FROM AUTHOR]

Background: The numbers of margin-negative resections and survival times have greatly improved because of a more aggressive surgical approach to resectable hilar cholanciocarcinoma (Klatskin tumour). It was shown initially by Japanese authors that complete resection of the caudate lobe together with partial hepatectomy leads to more margin-negative resections. However, this concept has not been unanimously taken up by Western authors. The aim of this study was to examine the role of complete caudate lobe resection in our series of resected hilar cholangiocarcinomas. Methods: Between January 1993 and January 2003, 54 patients underwent resection for Klatskin tumours. These patients were divided into two groups, according to the two 5-year periods in which they had been operated. In the first period, patients did not routinely undergo complete excision of the caudate lobe, whereas in the second period, partial liver resection was combined with complete excision of the caudate lobe in 15 patients. These two patient groups were evaluated with respect to postoperative morbidity and mortality, microscopic tumour margins and survival time. Results: Postoperative complications occurred in 59% of patients in total, while overall mortality was 11%. No difference was found in postoperative morbidity or mortality between the two periods. A significantly higher number of margin-negative resections was found in the second 5-year period, together with improved survival. Conclusion: Concomitant complete excision of segment 1 for patients with hilar cholangiocarcinoma did not lead to increased morbidity or mortality. Therefore the addition of complete excision of segment 1 is a safe procedure contributing to a higher rate of R0 resections and improved survival. [ABSTRACT FROM AUTHOR]

Background: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR).Study Design: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score.Results: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL).Conclusions: The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%. [ABSTRACT FROM AUTHOR]