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.

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.

Hyaluronic acid as a marker of hepatic sinusoidal obstruction syndrome secondary to oxaliplatin-based chemotherapy in patients with colorectal liver metastases.

BACKGROUND: A considerable number of patients develop sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy for colorectal liver metastases (CLMs). SOS is associated with adverse outcomes after major hepatectomy. Hyaluronic acid (HA) is a marker of hepatic sinusoidal endothelial cell function and may serve as an accurate marker of SOS. This study aimed to assess the value of systemic HA levels and fractional extraction (FE) of HA by the splanchnic area and liver as markers of SOS after oxaliplatin-based chemotherapy for CLMs. METHODS: Forty patients were studied. The presence of SOS was assessed histopathologically. Blood samples from the radial artery and portal and hepatic veins were collected. HA levels were determined by ELISA and the FE of HA was estimated. RESULTS: SOS was present in 23 patients, 11 of whom demonstrated moderate or severe SOS. Preoperative HA levels were significantly higher in patients with moderate or severe SOS (group B, n = 11) compared to patients with no or mild SOS (group A, n = 29) (51.6 ± 10.2 ng/mL vs. 32.1 ± 3.5 ng/mL, p = 0.030). A cutoff HA level of 44.1 ng/mL yielded a sensitivity of 67 % and specificity of 83 % for detection of SOS. The positive predictive value was 50 % and the negative predictive value 91 %. Both groups exhibited a similar FE of HA by the splanchnic area (-7.9 ± 8.5 % in Group A vs. 7.3 ± 3.6 % in Group B, p = 0.422) and liver (-10.7 ± 6.2 % in Group A vs. 4.6 ± 2.3 % in Group B, p = 0.265). CONCLUSIONS: Systemic HA levels can be used to detect patients at risk of SOS after oxaliplatin-based chemotherapy for CLMs. Additional investigations into the presence of SOS are indicated in patients with elevated HA levels.

Liver manipulation during liver surgery in humans is associated with hepatocellular damage and hepatic inflammation.

BACKGROUND: Manipulation of the liver during liver surgery results in profound hepatocellular damage. Experimental data show that mobilization-induced hepatocellular damage is related to hepatic inflammation. To date, information on this link in humans is lacking. As it is possible to modulate inflammation, it is clinically relevant to unravel this relationship. AIM: This observational study aimed to establish the association between liver mobilization and hepatic inflammation in humans. METHODS: Consecutive patients requiring mobilization of the right hemi-liver during liver surgery were studied. Plasma samples and liver biopsies were collected prior to and directly after mobilization and after transection of the liver. Hepatocellular damage was assayed by liver fatty acid-binding protein (L-FABP) and aminotransferase levels. Hepatic inflammation was determined by (a) immunohistochemical identification of myeloperoxidase (MPO) and CD68- positive cells and (b) hepatic gene expression of inflammatory and cell adhesion molecules (IL-1ß, IL-6, IL-8, VCAM-1 and ICAM-1). RESULTS: A total of 25 patients were included. L-FABP levels increased significantly during mobilization (301 ± 94 ng/ml to 1599 ± 362 ng/ml, P = 0.008), as did ALAT levels (36 ± 5 IU/L to 167 ± 21 IU/L, P < 0.001). A significant increase in MPO (P = 0.001) and CD68 (P = 0.002) positive cells was noticed in the liver after mobilization. The number of MPO-positive cells correlated with the duration of mobilization (Pearson correlation=0.505, P = 0.033). Hepatic gene expression of pro-inflammatory cytokines IL-1ß and IL-6, chemo-attractant IL-8 and adhesion molecule ICAM-1 increased significantly during liver manipulation. CONCLUSIONS: Liver mobilization is associated with hepatocellular damage and liver inflammation, as shown by infiltration of inflammatory cells and upregulation of genes involved in acute inflammation.

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.

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.

The flavonoid monoHER prevents monocrotaline-induced hepatic sinusoidal injury in rats.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) occurs in 50-70% of patients after oxaliplatin treatment for hepatic colorectal metastasis. SOS is associated with portal hypertension and is caused by oxidative damage to endothelial cells and matrix metalloproteinase (MMP) induction. We studied the effect of a flavonoid (monoHER) on SOS prevention. METHODS: A monocrotaline (MTC) SOS model was used in rats, with pre-treatment of monoHER. We studied hepatocellular damage and MMP expression. The potential inhibition of oxaliplatin cytotoxicity by monoHER was tested in vitro in colorectal cancer cell lines. RESULTS: MonoHER ameliorated the increase in portal pressure after MCT (72 hr: 7.3 ± 2.7 mmHg vs. 11.4 ± 3.0 mmHg, P = 0.016 MCT + monoHER vs. MCT, P < 0.01). MonoHER prevented hepatocellular damage (ALT: 48 hr 42.2 ± 3.1 IU/L vs. 253.4 ± 171.7 IU/L, P = 0.034; 72 hr: 46.2 ± 4.3 IU/L vs. 311.9 ± 163.6 IU/L, MCT + monoHER vs. MCT, P < 0.01). The liver damage score was lower in the monoHER group (72 hr: 4.8 ± 3.6 vs. 10.3 ± 0.5, MCT-monoHER vs. MCT, P < 0.01) associated with less inflammatory cell infiltration. Livers of MCT treated rats had higher expression of MMP-9 when compared to monoHER pairs at 24 hr (P = 0.016) and 72 hr (P < 0.001). MonoHER had no effect on in vitro proliferation of colorectal cancer cells when used either alone or in combination with oxaliplatin. CONCLUSIONS: MonoHER prevented MCT induced portal hypertension and hepatic injury in rats.

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.

Urinary ammonia excretion increases acutely during living donor liver transplantation.

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.

Gut and liver handling of interleukin-6 during liver resection in man.

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.

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/m(2) (versus a BMI > 25 kg/m(2), 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.

Virtual liver resection and volumetric analysis of the future liver remnant using open source image processing software.

BACKGROUND: After extended liver resection, a remnant liver that is too small can lead to postresection liver failure. To reduce this risk, preoperative evaluation of the future liver remnant volume (FLRV) is critical. The open-source OsiriX PAC software system can be downloaded for free and used by nonradiologists to calculate liver volume using a stand-alone Apple computer. The purpose of this study was to assess the accuracy of OsiriX CT volumetry for predicting liver resection volume and FLVR in patients undergoing partial hepatectomy. METHODS: Preoperative contrast-enhanced liver CT scans of patients who underwent partial hepatectomy were analyzed by three observers. Two surgical trainees measured the total liver volume, resection volume, and tumor volume using OsiriX, and a radiologist measured these volumes using CT scanner-linked Aquarius iNtuition software. Resection volume was correlated with prospectively determined resection weight, and differences in the measured liver volumes were analyzed. Interobserver variability was assessed using Bland-Altman plots. RESULTS: 25 patients (M/F ratio: 13/12) with a median age of 61 (range, 34-77) years were included. There were significant correlations between the weight and volume of the resected specimens (Pearson's correlation coefficient: R(2) = 0.95). There were no major differences in total liver volumes, resection volumes, or tumor volumes for observers 1, 2, and 3. Bland-Altman plots showed a small interobserver variability. The mean time to complete liver volumetry for one patient using OsiriX was 19 +/- 3 min. CONCLUSIONS: OsiriX liver volumetry performed by surgeons is an accurate and time-efficient method for predicting resection volume and FLRV.

Positive end-expiratory pressure induces liver congestion in living donor liver transplant patients: myth or fact.

Living-donated liver transplant (LDLT) patients may develop lung edema during reperfusion, requiring higher positive end-expiratory pressure (PEEP) levels, which may impair liver outflow. The aim of the study was to assess the effect of increased PEEP levels on venous liver outflow and systemic hemodynamics in patients after LDLT. Thirty-nine LDLT recipients were enrolled in this study. All patients were postoperatively pressure-controlled ventilated and three different PEEP levels (0, 5 and 10 mbar) were randomly set. Systemic hemodynamic parameters and flow velocities of the hepatic artery, portal vein, and right hepatic vein were recorded at each PEEP level. PEEP of 10 mbar increased significantly central venous and pulmonary capillary pressure. Flow velocities in the right hepatic vein, the portal vein, the hepatic artery, mean arterial pressure, pulmonary arterial pressure, and cardiac index were not influenced by PEEP. Our study demonstrated that PEEP up to 10 mbar did not impair liver outflow in LDLT recipients.

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.

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. 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.

Effects of Liver Resection on Hepatic Short-Chain Fatty Acid Metabolism in Humans.

AIM: To determine whether acute loss of liver tissue affects hepatic short-chain fatty acid (SCFA) clearance. METHODS: Blood was sampled from the radial artery, portal vein, and hepatic vein before and after hepatic resection in 30 patients undergoing partial liver resection. Plasma SCFA levels were measured by liquid chromatography-mass spectrometry. SCFA exchange across gut and liver was calculated from arteriovenous differences and plasma flow. Liver volume was estimated by CT liver volumetry. RESULTS: The gut produced significant amounts of acetate, propionate, and butyrate (39.4±13.5, 6.2±1.3, and 9.5±2.6 µmol·kgbw-1·h-1), which did not change after partial hepatectomy (p = 0.67, p = 0.59 and p = 0.24). Hepatic propionate uptake did not differ significantly before and after resection (-6.4±1.4 vs. -8.4±1.5 µmol·kgbw-1·h-1, p = 0.49). Hepatic acetate and butyrate uptake increased significantly upon partial liver resection (acetate: -35.1±13.0 vs. -39.6±9.4 µmol·kgbw-1·h-1, p = 0.0011; butyrate: -9.9±2.7 vs. -11.5±2.4 µmol·kgbw-1·h-1, p = 0.0006). Arterial SCFA concentrations were not different before and after partial liver resection (acetate: 176.9±17.3 vs. 142.3±12.5 µmol/L, p = 0.18; propionate: 7.2±1.4 vs. 5.6±0.6 µmol/L, p = 0.38; butyrate: 4.3±0.7 vs. 3.6±0.6 µmol/L, p = 0.73). CONCLUSION: The liver maintains its capacity to clear acetate, propionate, and butyrate from the portal blood upon acute loss of liver tissue.

[Is surgical scientific research substandard?]. / Is chirurgisch wetenschappelijk onderzoek ondermaats?

Randomized controlled trials (RCTs) are the gold standard for establishing the efficacy of surgical interventions. As the trial results are frequently incorporated in clinical guidelines, proper methodology and reporting of RCTs are essential. Trial protocol registration has been introduced, with the aim of improving the latter. A recent study by Hannink and colleagues showed that the quality of registration of surgical RCTs published in surgical journals was inferior to those published in medical journals. In addition, there was a discrepancy between registered and published outcome in approximately 50% of surgical trials. In this comment we critically assess the quality of surgical journals and surgical scientific research. Although there is still room for improvement, we conclude that major quality improvements have been made in these fields, such as the adoption of trial protocol registration by the editorial boards of high-impact surgical journals and the establishment of multidisciplinary study groups, which assure the future of evidence-based surgery.

Identification and validation of risk factors for postoperative infectious complications following hepatectomy.

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.

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.

Fixation methods for electron microscopy of human and other liver.

For an electron microscopic study of the liver, expertise and complicated, time-consuming processing of hepatic tissues and cells is needed. The interpretation of electron microscopy (EM) images requires knowledge of the liver fine structure and experience with the numerous artifacts in fixation, embedding, sectioning, contrast staining and microscopic imaging. Hence, the aim of this paper is to present a detailed summary of different methods for the preparation of hepatic cells and tissue, for the purpose of preserving long-standing expertise and to encourage new investigators and clinicians to include EM studies of liver cells and tissue in their projects.