Maartje A. J. van den Broek

Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment

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.

Pulmonary and Blood Stream Infections in Adult Living Donor and Cadaveric Liver Transplant Patients

Background. Infectious complications occur in approximately 50% of cadaveric liver transplant (CDLT) recipients. Living-donor liver transplantation (LDLT) is an established alternative to shorten the waiting time. Currently, the incidence of pulmonary infections after LDLT and the microbiologic causes are unknown. In the present cohort study, we compared the incidence and profiles of pulmonary and blood stream infections (BSI) between LDLT and CDLT recipients. We hypothesized a lower incidence in LDLT recipients. Methods. The clinical course of 55 LDLT recipients consecutively transplanted between January 2003 and December 2006 was analyzed. The 173 CDLT recipients who were transplanted in the same period served as a control group. Patients were treated in a single Intensive Care Unit, applying standardized postoperative care. Results. Mean model for end-stage liver disease score did not differ between LDLT and CDLT recipients (14.2 vs. 13.3). The overall incidence of pulmonary and BSI for both groups was 8% and 24%, respectively. Pulmonary infections were experienced by 18% of LDLT versus 5% of CDLT recipients (P=0.005) and BSI occurred in 33% of LDLT versus 21% of CDLT recipients (P=0.1). Conclusions. In contrast to our hypothesis, LDLT recipients experienced significantly more pulmonary infections and a trend toward increased higher incidence of BSI. These findings emphasize the need for future research on the causative agents and prevention of infection in LDLT recipients. The observation that patients with pulmonary infection had a significantly reduced 1-year survival rate underscores the importance of our observations.

Endothelial activation markers and their key regulators after restrictive bariatric surgery.

Objective: Increased plasma levels of endothelial activation markers in obese subjects reflect the positive association between cardiovascular diseases and obesity. The pro‐inflammatory state associated with obesity is thought to play a major role in endothelial cell activation in severely obese individuals. Previous studies demonstrated that long‐term weight loss after bariatric surgery is accompanied by a decreased proinflammatory state. However, little is known about the long‐term effects of bariatric surgery on endothelial cell activation.

Sarcopenia negatively affects preoperative total functional liver volume in patients undergoing liver resection.

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.

Randomized controlled trial analyzing the effect of 15 or 30 min intermittent Pringle maneuver on hepatocellular damage during liver surgery

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.

Outcomes of extended versus limited indications for patients undergoing a liver resection for colorectal cancer liver metastases.

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.

Hepatic sinusoidal obstruction syndrome (SOS) reduces the effect of oxaliplatin in colorectal liver metastases

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

Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia.

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

Procalcitonin as a prognostic marker for infectious complications in liver transplant recipients in an intensive care unit

Clinically significant infections (CSIs) are life‐threatening but difficult to diagnose after liver transplantation (LTx). This study investigates the value of procalcitonin (PCT) in addition to c‐reactive protein (CRP) and the leukocyte count (LC) as a prognostic marker for CSIs in LTx recipients. The clinical course of 135 LTx recipients was prospectively studied. CSIs were defined as pulmonary, bloodstream, or intra‐abdominal infections. Independent risk factors for CSIs were determined by Cox proportional hazard analysis. The concordance statistics (c‐statistics) were used to assess the discrimination effect of PCT. Thirty recipients (22%) experienced a CSI. They had significantly higher peak PCT (27.2 versus 12.7 ng/mL, P = 0.014) and peak CRP (13.7 versus 9.9 mg/dL, P < 0.001) and a tendency toward a higher peak LC (19.3 versus 14.2 cells/nL, P = 0.051) in comparison with recipients without CSIs. Independent risk factors for CSIs were male sex [hazard ratio (HR) = 6.4], a body mass index (BMI) < 20 kg/m2 (versus a BMI > 25 kg/m2, HR = 13.8), acute liver failure as an indication for LTx (HR = 7.1), a cold ischemic time > 420 minutes (HR = 3.5), and peak CRP (HR = 1.1) but not peak PCT. The addition of peak PCT marginally improved the c‐statistic from 0.815 to 0.827. In conclusion, although peak PCT differed significantly between recipients with and without CSIs, it was not an independent risk factor for CSIs and added little prognostic accuracy. Interestingly, the parameters peak CRP, male sex, low BMI, acute liver failure, and long cold ischemic time were independent risk factors for CSIs. They could serve as risk stratifiers directing medical therapy in clinical practice. Liver Transpl 16:402–410, 2010.

Hepatic Uptake of Rectally Administered Butyrate Prevents an Increase in Systemic Butyrate Concentrations in Humans

BACKGROUND Short-chain fatty acids (SCFAs), fermentation products of undigested fibers, are considered beneficial for colonic health. High plasma concentrations are potentially harmful; therefore, information about systemic SCFA clearance is needed before therapeutic use of prebiotics or colonic SCFA administration. OBJECTIVE The aim of this study was to investigate the effect of rectal butyrate administration on SCFA interorgan exchange. METHODS Twelve patients (7 men; age: 66.4 ± 2.0 y; BMI 24.5 ± 1.4 kg/m(2)) undergoing upper abdominal surgery participated in this randomized placebo-controlled trial. During surgery, 1 group received a butyrate enema (100 mmol sodium butyrate/L; 60 mL; n = 7), and the other group a placebo (140 mmol 0.9% NaCl/L; 60 mL; n = 5). Before and 5, 15, and 30 min after administration, blood samples were taken from the radial artery, hepatic vein, and portal vein. Plasma SCFA concentrations were analyzed, and fluxes from portal-drained viscera, liver, and splanchnic area were calculated and used for the calculation of the incremental area under the curve (iAUC) over a 30-min period. RESULTS Rectal butyrate administration led to higher portal butyrate concentrations at 5 min compared with placebo (92.2 ± 27.0 μmol/L vs. 14.3 ± 3.4 μmol/L, respectively; P < 0.01). In the butyrate-treated group, iAUCs of gut release (282.8 ± 133.8 μmol/kg BW · 0.5 h) and liver uptake (-293.7 ± 136.0 μmol/kg BW · 0.5 h) of butyrate were greater than in the placebo group [-16.6 ± 13.4 μmol/kg BW · 0.5 h (gut release) and 16.0 ± 13.8 μmol/kg BW · 0.5 h (liver uptake); P = 0.01 and P < 0.05, respectively]. As a result, splanchnic butyrate release did not differ between groups. CONCLUSION After colonic butyrate administration, splanchnic butyrate release was prevented in patients undergoing upper abdominal surgery. These observations imply that therapeutic colonic SCFA administration at this dose is safe. The trial was registered at clinicaltrials.gov as NCT02271802.