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Introduction: The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. Methods: PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO2 and liver parenchymal VEGF were assessed. Results: Eleven rabbits were included after PVE (R-PVE, n = 5; P-PVE, n = 6). TVD in the nonembo-lized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm2; p < 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO2 and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. Discussion/Conclusion: Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE. [ABSTRACT FROM AUTHOR]

The microcirculation plays a crucial role in the distribution of perfusion to organs. Studies have shown that microcirculatory dysfunction is an independent predictor of morbidity and mortality. Hence, assessment of liver perfusion offers valuable information on the (patho)physiological state of the liver. The current review explores techniques in perfusion imaging that can be used intraoperatively. Available modalities include dynamic contrast-enhanced ultrasound, handheld vital microscopes, indocyanine green fluorescence angiography, and laser contrast speckle imaging. Dynamic contrast-enhanced ultrasound relays information on deep tissue perfusion and is a commonly used technique to assess tumor perfusion. Handheld vital microscopes provide direct visualization of the sinusoidal architectural structure of the liver, which is a unique feature of this technique. Intraoperative fluorescence imaging uses indocyanine green, a dye that is administered intravenously to visualize microvascular perfusion when excited using near-infrared light. Laser speckle contrast imaging produces non-contact large surface-based tissue perfusion imaging free from movement- or pressure-related artefacts. In this review, we discuss the intrinsic advantages and disadvantages of these techniques and their clinical and/or scientific applications. [ABSTRACT FROM AUTHOR]

Background: Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic strictures, recurrent cholangitis, and secondary biliary cirrhosis. Methods: We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients. Results: Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after "clinically successful" treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10–20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%. Conclusions: The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to apply an innovative methodology to incident dark-field (IDF) imaging in coronary artery bypass grafting (CABG) patients for the identification and quantification of rolling leukocytes along the sublingual microcirculatory endothelium. Methods: This study was a post hoc analysis of a prospective study that evaluated the perioperative course of the sublingual microcirculation in CABG patients. Video images were captured using IDF imaging following the induction of anesthesia (T0) and cardiopulmonary bypass (CPB) (T1) in 10 patients. Rolling leukocytes were identified and quantified using frame averaging, which is a technique that was developed for correctly identifying leukocytes. Results: The number of rolling leukocytes increased significantly from T0 (7.5 [6.4–9.1] leukocytes/capillary-postcapillary venule/4 s) to T1 (14.8 [13.2–15.5] leukocytes/capillary-postcapillary venule/4 s) (p < 0.0001). A significant increase in systemic leukocyte count was also detected from 7.4 ± 0.9 × 109/L (preoperative) to 12.4 ± 4.4 × 109/L (postoperative) (p < 0.01). Conclusion: The ability to directly visualize leukocyte-endothelium interaction using IDF imaging facilitates the diagnosis of a systemic inflammatory response after CPB via the identification of rolling leukocytes. Integration of the frame averaging algorithm into the software of handheld vital microscopes may enable the use of microcirculatory leukocyte count as a real-time parameter at the bedside. [ABSTRACT FROM AUTHOR]

Clips inserted during laparoscopic cholecystectomy (LC) may migrate into the biliary system and function as a nidus for the formation of gallstones. Here, we present a series of 4 patients who presented with this rare complication 5–17 years after LC. All 4 patients presented with symptomatic choledocholithiasis with biochemical and radiological signs of biliary obstruction. Three patients also had fever and infectious parameters, compatible with concurrent cholangitis. All patients successfully underwent endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy and stone extraction. Patients with cholangitis also had antibiotic treatment. In 3 patients, obstruction of the common bile duct was caused by a single, relatively large stone that had formed around a clip (supposedly the cystic duct clip). In 1 patient, multiple stones had formed around an intrabiliary migrated cluster of coils that had been used for arterial embolization of a pseudo-aneurysm of the right hepatic artery. In conclusion, surgical clips and coils can migrate into the biliary tract and serve as a nidus for the formation of bile duct stones. Although rare, this complication should caution surgeons not to place clips "at random" during cholecystectomy. Patients with this rare complication are best managed by ERCP in combination with sphincterotomy and stone extraction. [ABSTRACT FROM AUTHOR]

Background/Aims: For applicability of cell-based therapies aimed at the treatment of liver failure, such as bioartificial livers (BALs) and hepatocyte transplantation, it is essential that the applied hepatocytes tolerate exposure to the patient plasma. However, plasma from both healthy donors and acute liver failure (ALF) patients is detrimental to hepatocytes and hepatic cell lines, such as HepaRG. We aimed to elucidate the underlying mechanisms of plasmainduced toxicity against HepaRG cells in order to ultimately develop methods to reduce this toxicity and render HepaRG-BAL treatment more effective. Methods: Differentiated HepaRG cells cultured in monolayers and laboratory-scale BALs were exposed to culture medium, healthy human plasma, healthy porcine plasma and ALF porcine plasma. Healthy human plasma was fractionated based on size- and polarity, albumin depleted and heat treated to characterize the toxic fraction. The cells were assessed for viability by total protein content and trypan blue staining. Their hepatic differentiation was assessed on transcript level through qRT-PCR and microarray analysis, and on functional level for Cytochrome P450 3A4 activity and ammonia elimination. Mitochondrial damage was assessed by JC-1 staining and mitochondrial gene transcription. Results: Sixteen hours of healthy human plasma exposure did not affect viability, however, hepatic gene-transcript levels decreased dramatically and dose-dependently within four hours of exposure. These changes were associated with early NF-kB signaling and a shift from mitochondrial energy metabolism towards glycolysis. Healthy human plasma-toxicity was associated with the dose-dependent presence of heat-resistant, albumin-bound and (partly) hydrophobic toxic compound(s). HepaRG cells cultured in BALs were partially protected from plasma-toxicity, which was mainly attributable to medium perfusion and/or 3D configuration applied during BAL culturing. The detrimental human plasma effects were reversible in BALcultured cells. Porcine ALF-plasma elicited mitotoxicity additional to the basal detrimental effect of porcine healthy plasma, which were only partially reversible. Conclusion: A specific fraction of human plasma reduces hepatic differentiation of HepaRG cultures, in association with early NF-κB activation. In addition, ALF-plasma elicits mitotoxic effects. These findings allow for a targeted approach in preventing plasma-induced cell damage. [ABSTRACT FROM AUTHOR]

Background/Aims: This study describes the peritoneal microcirculation, compares quantitative parameters and angioarchitecture to the standard of sublingual microcirculatory assessment, and determines the practical feasibility of this method. Methods: Incident dark field imaging was performed of the peritoneum and sublingually to determine angioarchitecture, total and perfused vessel density (TVD and PVD), the proportion of perfused vessels (PPV), the microvascular flow index (MFI) and image acquisition time. Results: Peritoneal angioarchitecture was characterized by a quadrangular network of longitudinally oriented capillaries, often flanked by fat cells. Differences between peritoneal and sublingual microcirculation were observed with regard to TVD (peritoneum 12 mm/mm2 [95% CI 10–14] vs. sublingual 23 mm/mm2 [95% CI 21–25]; p < 0.0001), PVD (peritoneum 11 mm/mm2 [95% CI 9–13] vs. sublingual 23 mm/mm2 [95% CI 21–25]; p < 0.0001), PPV (peritoneum 88% [95% CI 79–97] vs. sublingual 99% [95% CI 99–100]; p = 0.014), and MFI (peritoneum 3 [IQR 2.3–3.0] vs. sublingual 3 [IQR 3.0–3.0]; p = 0.012). There was no difference in image acquisition time (peritoneum 2: 34 min [95% CI 1: 49–3: 19] vs. sublingual 2: 38 [95% CI 1: 37–3: 32]; p = 0.916). Conclusion: The peritoneal microcirculation was characterized by a low capillary density and a distinctive angioarchitecture. The possibility of peri­toneal microcirculatory assessment offers promise for the study of peritoneal (patho-)physiology and (monitoring or detection of) associated diseases. [ABSTRACT FROM AUTHOR]

A 73-year-old male presented with jaundice and severe muscle weakness. He was diagnosed with distal cholangiocarcinoma and paraneoplastic necrotizing autoimmune myopathy (NAM). Treatment of NAM consisted of dexamethasone pulse therapy, prednisone, and single-dose intravenous immunoglobulin. The distal cholangiocarcinoma was resected through a total laparoscopic pancreatoduodenectomy. After hospital discharge, muscle strength initially increased postoperatively; however, pneumonia resulted in the deterioration of his general condition and death 5 months after the diagnosis of paraneoplastic NAM. [ABSTRACT FROM AUTHOR]

ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new surgical technique for patients in whom conventional treatment is not feasible due to insufficient future remnant liver (FRL). During the first stage of ALPPS, accelerated hypertrophy of the FRL is induced by ligation of the portal vein and in situ split of the liver. In the second stage, the deportalized liver is removed when the FRL volume has reached ≥25% of total liver volume. However, FRL volume does not necessarily reflect FRL function. 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) with SPECT-CT is a quantitative test enabling regional assessment of parenchymal uptake function using a validated cut-off value for the prediction of postoperative liver failure (2.7%/min/m2). This paper describes the changes in FRL function and FRL volume in a 79-year-old patient diagnosed with metachronous colonic liver metastases who underwent ALPPS. We have observed a substantial difference between the increase in FRL volume and FRL function suggesting that HBS with SPECT-CT enables monitoring of the FRL function and could be a useful tool in the timing of resection in the second stage of the ALPPS procedure. [ABSTRACT FROM AUTHOR]

Artificially induced hypometabolism in nonhibernating mammals may have considerable clinical implications. Numerous studies in small rodent models have demonstrated that hydrogen sulfide (H2S) induces hypometabolism, supposedly as a result of histotoxic hypoxia. However, the induction of hypometabolism is absent in large animals following H2S administration. To determine the cause of this animal size-dependent discrepancy in H2S pharmacodynamics, the effects of sodium H2S (NaSH; 5 mg/kg/h, 4-hour intravenous administration) on systemic, pneumocardial, hematological, biochemical, microvascular (sublingual), and histological parameters were investigated in pigs. After 4 h, no differences were observed between the NaSH and control group with respect to systemic, pneumocardial, hematological, biochemical, and histological parameters. However, NaSH triggered significant hyperperfusion in the sublingual microcirculation, as evidenced by an increased blood vessel diameter (154 ± 16 and 85 ± 25% vs. baseline for NaSH and NaCl, respectively), total vessel density (139 ± 18 and 98 ± 13%, respectively), and perfused vessel density (139 ± 18 and 99 ± 13%, respectively). These phenomena are consistent with microvascular changes that occur during a panting response, an important heat loss mechanism (i.e., thermoregulatory effector) in pigs that is controlled by the thermoneutral zone (Ztn). On the basis of our findings and the literature, a mechanistic explanation is provided for the differential manifestation of hypometabolism between small and large animals. In large animals, H2S does not act via histotoxic hypoxia but likely triggers carotid bodies to transmit a hypoxic signal, which subsequently lowers the Ztn and activates heat loss mechanisms (e.g., panting) to align ATP consumption with ATP production through hypothermia. Since large animals have a small surface:size ratio, the cooling rate is too inefficient to accommodate hypothermia and subsequent hypometabolism. This is why large animals do not exhibit hypometabolism, despite the activation of thermoregulatory effectors. This is also a reason for the poor translatability of artificial hypometabolism to the clinical setting. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Chromogranin A (CgA) is often used in metastatic patients with nonfunctioning pancreatic neuroendocrine tumors (NF-pNET). The aim of this study is to assess the diagnostic accuracy of CgA in patients with low tumor burden. Methods: Resectable patients with NF-pNET without metastases at time of diagnosis were included between 2002 and 2013 in the Academic Medical Center of Amsterdam. CgA was determined at time of diagnosis and during follow-up according to a standardized method. The upper reference range was 94 µg/l. Results: Overall, 47 patients were included in this study. CgA was elevated preoperatively in only 10 patients (27%). In the detection of metastases during follow-up, the positive predictive value for CgA was 50% and negative predictive value was 81%. In 50% of the patients with an elevated CgA during follow-up, this test result was false-positive. Conclusions: The diagnostic accuracy of CgA was low preoperatively in patients with resectable NF-pNET and low tumor burden. In the detection of recurrent disease after curative resection of NF-pNET, the diagnostic accuracy of CgA was moderate (50%). We conclude that the routine measurement of CgA at time of diagnosis or during follow-up after curative resection had limited value in patients with resectable NF-pNET. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In order to achieve microscopic radical resection margins and thus better survival, surgical treatment of hepatic tumors has become more aggressive in the last decades, resulting in an increased rate of complex and extended liver resections. Postoperative outcomes mainly depend on the size and quality of the future remnant liver (FRL). Liver resection, when performed in the absence of sufficient FRL, inevitably leads to postresection liver failure. The current gold standard in the preoperative assessment of the FRL is computed tomography volumetry. In addition to the volume of the liver remnant after resection, postoperative function of the liver remnant is directly related to the quality of liver parenchyma. The latter is mainly influenced by underlying diseases such as cirrhosis and steatosis, which are often inaccurately defined until microscopic examination after the resection. Postresection liver failure remains a point of major concern that calls for accurate methods of preoperative FRL assessment. A wide spectrum of tests has become available in the past years, attesting to the fact that the ideal methodology has yet to be defined. The aim of this review is to discuss the current modalities available and new perspectives in the assessment of FRL in patients scheduled for major liver resection. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of gallbladder carcinoma (GBC). However, there is no evidence for the benefit of this costly practice. Our aim was to determine whether a selective strategy based on macroscopic appearance of gallbladder specimens is a reliable strategy to exclude them from histopathological examination. Methods: A retrospective study was conducted from January 2007 until November 2011 in a large community hospital in the Netherlands. All gallbladder specimen reports (n = 1,393) after cholecystectomy were included and searched for abnormal findings. Reports were excluded when a full histopathological report was not available (n = 18). Results: Out of the 1,375 patients, 185 had a macroscopically abnormal gallbladder specimen. Of these patients, 6 had GBC. All patients with GBC had macroscopic abnormalities, giving a negative predictive value of 100% to exclude gallbladder specimens from histopathological examination based on macroscopic abnormalities. Conclusions: Based on our study it seems justified to exclude gallbladder specimens from histopathological examination based on the absence of macroscopic abnormalities. A more selective policy will reduce medical costs, saving EUR 1.3 million a year in the Netherlands alone, whilst maintaining patient safety. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion (I/R) models have shown that C-reactive protein (CRP) and immunoglobulin M (IgM) are involved in complement activation. Binding of CRP and IgM to damaged cell membranes initiates complement activation and aggravates I/R injury in various organs. However, the time course of CRP- and IgM-mediated complement activation and the relation to hepatocellular injury and inflammation in liver I/R are unknown. Aim: To evaluate the time course of IgM- and CRP-related complement activation and the relation to hepatocellular injury and inflammation in a hepatic I/R rat model. Methods: Male Wistar rats were allocated to (1) five groups of animals exposed to 60 min of partial ischemia (70%) induced via clamping of the left segmental portal triad, followed by 0, 3, 6, 12 or 24 h of reperfusion (n = 6 in each group); (2) five groups of sham-operated animals with corresponding reperfusion times (n = 5), and (3) a control group sacrificed before ischemia (n = 5). Hepatocellular injury, inflammatory response, rat plasma CRP and IgM levels and immunohistochemical depositions of CRP, IgM and C3 were assessed for each group. Results: Histopathological injury scores of hematoxylin and eosin sections of ischemic liver lobes demonstrated increasing values throughout the reperfusion time with a peak at 12 h. Plasma aminotransferases (alanine aminotransferase and aspartate aminotransferase) significantly increased after 3 h of reperfusion, peaking at 6 h (3,100 ± 800 U/l; p < 0.05). Hepatic neutrophil influx significantly increased from 3 to 6 h of reperfusion (p < 0.05) and demonstrated the highest value at 12 h (1.1 ± 0.2 U/mg of protein). Plasma IL-6 levels in the ischemia groups showed peak values after 6 h of reperfusion, decreasing significantly thereafter (p < 0.05). Plasma CRP values reached highest levels after 3 h of reperfusion (mean 91 ± 5% of control pool), decreasing significantly thereafter. Rat IgM concentrations in plasma did not significantly change throughout the reperfusion time. Immunohistochemical depositions of IgM, CRP and C3 in ischemic lobes demonstrated a similar pattern in time, reaching maximum values at 12 h of reperfusion. The percentages of depositions of CRP and IgM were significantly correlated [r(S) = 0.569; p < 0.001; Spearman test]. The time course of C3 and CRP depositions throughout reperfusion and C3 and IgM staining were significantly similar [r(S) = 0.797 and r(S) = 0.656, respectively; p < 0.0001; ANOVA]. Conclusions: CRP and IgM depositions demonstrate a parallel time course throughout the reperfusion to hepatocellular damage, inflammatory response and activated complement deposition in this rat hepatic I/R model. Furthermore, the time course of CRP and IgM depositions was significantly similar to that of activated complement depositions. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Centralization of complex upper gastrointestinal (GI) surgery and the effect on postoperative outcomes, especially mortality, has been reported extensively in the literature. In this review the highest level of evidence on the volume outcome relationship is discussed together with other important aspects that can influence postoperative outcomes. Do high-volume centers and surgeons result in better outcomes after surgery for the different upper GI surgical procedures such as esophageal, gastric, liver and pancreatic tumors? Twelve systematic reviews including four meta-analyses described the effect of hospital and/or surgeon volume on mortality. The majority of reviews (>90%) showed a lower mortality in high-volume hospitals. This correlation was also reported when analyzing the different GI procedures separately for esophageal, gastric, hepatic and pancreatic tumors. The volume discussion has limitations and therefore the relationship between hospital structure and process of care in hospitals and the outcome of surgery has also been acknowledged. Besides surgeon expertise and skills, high-intensity intensive care units, 24/7 availability of interventional radiology, effective prevention and managing of complications and adequate patient selection will influence postoperative outcomes. These forms of hospital structures and process of care might even play a more important role in surgical outcomes. Copyright © 2012 S. Karger AG, Basel [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/Aims: There are several imaging modalities available for the detection of focal liver lesions. Differentiation between focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) is important because of the consequences for management. However, differentiation based on imaging alone still shows limitations. Methods: We reviewed the literature for typical features of FNH and HCA on radiologic and nuclear imaging with emphasis on differentiation of both lesions. Results: Seven articles describe the performance of an imaging modality for the differentiation between FNH and HCA. Limitations of these studies are the small sample size and/or the lack of comparison with the ‘gold standard’, i.e. histological diagnosis. No studies are available that compare the accuracy of several imaging modalities in the differentiation of FNH and HCA. Conventional ultrasound (US) is not useful in the differentiation because of the non-specific features. On contrast-enhanced US, the arterial filling direction of FNH is centrifugal and centripetal in case of HCA. The parenchymal enhancement of FNH is sustained in the portal venous and delayed phases, but shows rapid washout in case of HCA. Multiphase CT scan can differentiate FNH from HCA when there is a central scar. FNH may have a slightly higher relative enhancement in the arterial phase. On MRI with hepatocyte-specific contrast agents, HCA does not show contrast uptake in the hepatobiliary phase in contrast to FNH. Conclusion: We conclude that there is limited evidence of the diagnostic performance of currently used imaging modalities for the differentiation of FNH and HCA. We therefore propose a prospective study (DiFA trial) to determine the accuracy of several radiologic and nuclear imaging studies in differentiating FNH and HCA. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: Local recurrence and needle track seeding are serious complications after local ablation for liver malignancies and potentially affect long-term survival. The aim of this study was to assess the incidence of viable tissue adherent to the needle applicators after ablation to gain insight into the possible mechanisms of local recurrence and needle track seeding. Methods: A total of 40 consecutive patients underwent 59 local liver ablations. Cells and tissue attached to the needle applicators were analysed for morphology (HE, PAP and Giemsa staining) and viability (G6PD staining). Results: Macroscopic tissue adherence was visible following 31 of the ablative procedures, all with radiofrequency ablation. Four applications were performed percutaneously and 27 during an open procedure. Morphologically intact tumour cells could be identified in 8 patients (20%), and viable tumour cells in 5 patients (12.5%). Morphologically intact tumour cells or viable tumour cells could only be demonstrated when track ablation was not performed. Conclusion: Viable tumour cells adherent to the needle applicators were found in an alarming 12.5% of patients after local ablation. We recommend track ablation not only after the procedure but also during any shifting and (re-)positioning to prevent shedding of viable tumour cells during or after ablation. Copyright © 2009 S. Karger AG, Basel [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]

Background: Mechanisms underlying hepatic zonation are not completely elucidated. In vitro test systems may provide new insights into current hypotheses. In this study, zonally expressed proteins, i.e. glutamine synthetase (GS; pericentral) and carbamoylphosphate synthetase (CPS; periportal), were tested for their expression patterns in the bioartificial liver of the Academic Medical Center (AMC-BAL). Methods: Distribution and organization of porcine hepatocytes inside the AMC-BAL as well as GS and CPS expression were analyzed (immuno-)histochemically in time. Ten zonally expressed proteins were analyzed by RT-PCR on cell isolate and bioreactor samples. General metabolic and hepatocyte-specific functions were determined as well. Results: Viable hepatocyte layers of approximately 150 μm were observed around gas capillaries, whereas inside the matrix, single cells or small aggregates were present. GS protein and mRNA levels were upregulated in time. GS protein was preferentially expressed in hepatocytes adjacent to oxygen-supplying capillaries and in previously CPS-positive hepatocytes. No shift towards a periportal or pericentral phenotype was observed from RT-PCR analysis. Conclusion: Induction of GS expression inside the AMC-BAL is not dependent of (low) oxygen tensions and hepatic nuclear factor 4α transcript levels. GS expression might be related to (1) low substrate levels and/or autocrine soluble factors, or (2) to cytoskeleton interactions, putatively associated with the β-catenin signaling pathway. Copyright © 2008 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]

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 introduces the issue that focuses on the treatment of liver metastasis and the role of chemotherapy in surgical strategies.

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.