Comparison between dynamic gadoxetate-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT for quantitative assessment of liver function.

OBJECTIVES: To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. METHODS: Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. RESULTS: A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863-0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki. CONCLUSIONS: Assessment of liver function with DHCE-MRI is comparable with that of 99mTc-mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery. KEY POINTS: • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

[Local approval procedures act as a brake on RCTs]. / Lokale toestemmingsprocedures zetten een rem op RCT's.

OBJECTIVE: Large multicentre randomised controlled trials (RCTs) in the Netherlands are increasingly being impeded by major differences between local approval procedures. However, no national agenda exists as yet to improve this situation. The existence of major local differences in processing time and documentation required has been reported previously but little is known about the costs incurred and whether or not specific certifications and research contracts are mandatory. The current study evaluated these aspects of local procedures for obtaining approval of two oncological multicentre RCTs. DESIGN: Retrospective, descriptive. METHOD: All local procedures for obtaining approval of two randomised clinical trials were evaluated: the CAIRO5 and CHARISMA trials initiated by the Dutch Colorectal Cancer Group (DCCG). We objectified time between approval by the Medical Ethics Review Committee (METC) and final approval by the Board of Directors (RvB), the type and number of documents needed, and costs charged. RESULTS: The median time interval between the approval by the Medical Ethics Review Committee and the approval by the Board of Directors was 90 days (range 4-312). The number of documents required per centre ranged from 6-20. The costs charged ranged from € 0-€ 1750, and amounted to € 8575 for all procedures combined. No costs were charged by the majority of the centres. CONCLUSION: The approval procedures for multicentre clinical trials in the Netherlands demonstrate major differences. Processing times, documentation required and costs are unpredictable; greater uniformity is highly desirable in this context.

Hepatic steatosis assessment with CT or MRI in patients with colorectal liver metastases after neoadjuvant chemotherapy.

PURPOSE: Preoperative radiological assessment of hepatic steatosis is recommended in patients undergoing a liver resection, but few studies investigated the diagnostic accuracy after neoadjuvant chemotherapy. The aim of this study was to compare diagnostic accuracy of preoperative CT or MRI measurements of steatosis in patients with colorectal liver metastases after induction chemotherapy. METHODS: MRI measurements (relative signal intensity decrease; RSID), N = 36, and CT scan measurements (Hounsfield units; HU), N = 32, were compared with histological steatosis assessment. Diagnostic accuracy was determined for detecting any (>5%) or marked macrovesicular steatosis (>33%). RESULTS: MRI showed the highest correlation with histology (r = 0.82, P < 0.001), compared to CT measurements (r = -0.65, P < 0.001). Based on linear regression analysis, radiological cut-off values for 5% and 33% macrovesicular steatosis, corresponded to 0.7% and 19.2% RSID in the MRI-group, and 60.4 and 54.2 HU in the CT-group, respectively. Sensitivity and specificity for the detection of any and marked macrovesicular steatosis using MRI was 87% and 69%, and 78% and 100%, respectively, and for CT, 83% and 64%, and 70% and 87%, respectively. CONCLUSION: In patients treated with neoadjuvant chemotherapy MRI measurements of steatosis showed the highest correlation coefficient and the best diagnostic accuracy, as compared to CT measurements.

Incidence and management of bile leakage after partial liver resection.

BACKGROUND/AIMS: Bile leakage after partial liver resection still is a common complication and is associated with substantial morbidity and even mortality. METHODS: A total of 234 consecutive liver resections without biliary reconstruction, performed between January 1992 and December 2004, were analyzed for postoperative bile leakage. RESULTS: Postoperative bile leakage occurred in 6.8% of patients (16/234). In univariate analysis, male gender (p = 0.037), major liver resection (p = 0.004), right-sided hepatectomy (p = 0.005), prolonged operation time (p = 0.001), intraoperative blood loss >500 ml (p = 0.009), red cell transfusion (p = 0.02), tumor size (p = 0.026), duration of vascular occlusion (p = 0.03) and surgical irradicality (p = 0.001) were risk factors. No independent risk factors were associated with bile leakage after liver resection. Bile leakage originated from the resection plane in 10 patients (63%). Endoscopic biliary decompression was performed in 9 patients as initial treatment, and percutaneous drainage of the bile collection was used in 4 patients. Bile leakage resolved spontaneously in 3 patients. CONCLUSIONS: Bile leakage is a persisting complication and in this study occurred in 6.8% of patients after partial liver resection. Percutaneous drainage of bile collection with or without endoscopic biliary decompression are effective interventions in the management of most cases of bile leakage.

Assessment of systemic inflammatory response (SIR) in patients undergoing radiofrequency ablation or partial liver resection for liver tumors.

INTRODUCTION: Local therapies for liver tumors are considered to be safe. However, cryoablation (CA) has been associated with an exaggerated systemic inflammatory response (SIR). Aim of this study was to assess the degree of SIR after radiofrequency ablation (RFA) in comparison with major (MR) or minor (mR) liver resection. MATERIAL AND METHODS: Thirty-nine patients were treated with RFA (n = 11), MR (n = 10) or mR (n = 18). SIR parameters [white blood count (WBC) and C-reactive protein (CRP)], proinflammatory mediators [IL-6, TNF-alpha and sPLA2], liver damage parameters [AST/ALT] and platelet counts were determined at different time points. The volume of ablated liver was calculated on the first CT after RFA in order to correlate ablated liver volume with liver enzyme release and SIR. All data are expressed as median values with quartiles [25%, 75%]. RESULTS: RFA induced a moderate SIR, as demonstrated by a significant elevation of CRP (77 mg/L vs 3 mg/L), IL-6 (96 pg/ml vs 4 pg/ml) and sPLA2 (41 ng/ml vs 7 ng/ml, p < 0.05). Peak point values of SIR (WBC and CRP at 24 vs 48 h and 48 vs 72 h) and proinflammatory response parameters (24 vs 48 h) occurred earlier after RFA than after mR or MR. Time-to-time comparison revealed even increased levels of CRP (77 mg/L [59, 160]) 24h after RFA when compared to patients undergoing major or minor resection (50 mg/L [28, 66] and 59 mg/L [24, 91], respectively) and increased levels of IL-6 (67 pg/ml [42, 131]) 4 h after RFA when compared to patients undergoing minor resection (29 pg/ml [20, 55]). Postoperative levels of AST and LDH correlated significantly with the ablated liver volume 1h after RFA (RC = 0.860 and RC = 0.868, respectively, p < 0.05). CONCLUSION: RFA induced a moderate SIR of the same magnitude as in patients undergoing partial liver resection. None of the patients showed signs of an exaggerated SIR, as has been reported after cryoablation.

Assessment and improvement of liver specific function of the AMC-bioartificial liver.

UNLABELLED: The variety of methods for measuring bioactive mass and functionality of bioartificial livers (BAL) is confusing and prevents accurate comparison of reported data. Here we present a comparison of different hepatocyte quantification methods and propose that estimation of cell pellet volume after centrifugation generates a reliable, useful and fast method. In addition a correlation is made between several function tests performed in 26 bioreactors to assess their predictive value. The ammonia eliminating capacity was found to be most predictive for other liver functions, except for lidocaine elimination as a measure of mixed function oxidase activity, which should therefore be determined separately. The oxygen consumption test proved to be an easy and predictive parameter as well. The first generation of our BAL system needed further development to assure optimal treatment of acute liver failure (ALF) patients. Changes in the porcine hepatocyte isolation method and bioreactor loading as well as changes in bioreactor configuration, including use of different materials, resulted in a significantly improved level and maintenance of in vitro BAL function. A fourfold increase in ammonia eliminating capacity, which is only reduced to 75% after seven days of culturing, offers promising prospects for further clinical application. CONCLUSION: The current second generation of our BAL and improvement of hepatocyte isolation and testing protocols have led to a significant increase in the level as well as the maintenance of hepatocyte specific function in our BAL. Finally, consensus on definition of the bioactive mass to be loaded in the bioreactor and insight in the variation and reliability of the functional and metabolic parameters enhances comparison of the different types of bioartificial livers presented in literature.

Incidence and management of pancreatic leakage after pancreatoduodenectomy.

BACKGROUND: Optimal management of severe pancreatic leakage after pancreatoduodenectomy can reduce morbidity and mortality. Completion pancreatectomy may be adequate but leads to endocrine insufficiency. This study evaluated an alternative management strategy for pancreatic leakage. METHODS: Outcome after disconnection of the jejunal limb, resection of the pancreatic body and preservation of a small pancreatic remnant, performed between 1997 and 2002, was compared with that after completion pancreatectomy performed between 1992 and 1996. RESULTS: Pancreatoduodenectomy was performed in 459 consecutive patients. Pancreatic leakage occurred in 41 patients (8.9 per cent); its incidence did not change over the study period. Non-surgical drainage procedures were performed in 14 patients, of whom one died, and surgical drainage in eight patients, of whom two died. Completion pancreatectomy was performed in nine patients with no deaths. A pancreatic remnant was preserved in ten patients, of whom three died. A remnant tail had to be resected in two patients and three patients still developed endocrine insufficiency ('brittle' diabetes). CONCLUSION: The incidence of pancreatic leakage did not change over the study interval. Preservation of a small pancreatic tail was associated with higher morbidity and mortality rates than those of completion pancreatectomy.

Continuous or intermittent vascular clamping during hemihepatectomy in pigs: hyaluronic acid kinetics in the assessment of early microvascular liver damage.

OBJECTIVE: To assess the uptake of hyaluronic acid (HA) as a marker of microvascular damage in a model of hemihepatectomy in pigs having continuous or intermittent vascular inflow occlusion. DESIGN: Prospective, animal study. SETTING: Laboratory for experimental surgery, University hospital, The Netherlands. INTERVENTIONS: Total liver ischaemia was achieved during 90 minutes by continuous (n = 5) or intermittent (n = 5) occlusion of the portal vein and hepatic artery followed by 120 minutes of reperfusion. In a second series of pigs (n = 8) a left hemihepatectomy was added to the protocol. MAIN OUTCOME MEASURES: Uptake of exogenous HA was assessed before ischaemia and after 120 minutes of reperfusion, together with the galactose elimination capacity. Plasma activities of aspartate aminotransferase (AST), alanine amino transferase, and lactate dehydrogenase were measured and specimens of liver were obtained for histopathological examination. RESULTS: HA uptake was slightly reduced after reperfusion in unresected livers compared with uptake before ischaemia. After hemihepatectomy HA uptake after reperfusion was significantly reduced after both continuous and intermittent occlusion, but more HA was taken up after continuous occlusion (p = 0.02). Release of AST after reperfusion was increased only after hemihepatectomy. CONCLUSIONS: Microvascular damage, as assessed by HA uptake capacity, significantly contributed to normothermic ischaemia and reperfusion injury in porcine liver. Vascular inflow occlusion during 90 minutes in combination with hemihepatectomy resulted in less liver damage when vascular occlusion was continuous rather than intermittent.

Hyaluronic acid uptake in the assessment of sinusoidal endothelial cell damage after cold storage and normothermic reperfusion of rat livers.

The uptake of hyaluronic acid (HA) was used to assess preservation damage to sinusoidal endothelial cells (SEC) during cold storage and subsequent normothermic reperfusion of rat livers. After 8, 16, 24, and 48 h storage in University of Wisconsin (UW) solution, livers were gravity-flushed via the portal vein with a standard volume of cold UW solution containing 50 micrograms/l HA. The effluent was collected for analysis of HA, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). The mean uptake of HA at 0 h was 59.1% +/- 4.6% (mean +/- SEM). After 8 h of storage, HA uptake was similar (55.5% +/- 7.3%), whereas after 16 h of storage it was reduced to 34.7% +/- 5.8%. At 24 and 48 h of storage, no uptake of HA was found. In a second series of experiments, livers were stored in UW solution and subsequently reperfused for 90 min with a Krebs-Henseleit solution (37 degrees C) in a recirculating system containing 150 micrograms/l HA. Following 8 h of storage, 34.6% +/- 8.0% of the initial HA concentration was taken up from the perfusate. After 16 and 24 h of storage, no uptake of HA was found. The results of this study indicate that damage to SEC occurs progressively during storage, leading to zero uptake of HA by the rat livers at 24 h of cold ischemia time. Additional reperfusion injury to the SEC was demonstrated by the reduced ability of the SEC to take up HA following normothermic reperfusion. The uptake of exogenous HA in preserved livers, used as a tool to assess SEC injury, enables the detection of early preservation damage.