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One approach of regenerative medicine to generate functional hepatic tissue in vitro is decellularization and recellularization, and several protocols for the decellularization of livers of different species have been published. This appears to be the first report on rat liver decellularization by perfusion under oscillating pressure conditions, intending to optimize microperfusion and minimize damage to the ECM. Four decellularization protocols were compared: perfusion via the portal vein (PV) or the hepatic artery (HA), with (+P) or without (-P) oscillating pressure conditions. All rat livers (n = 24) were perfused with 1% Triton X-100 and 1% sodium dodecyl sulphate, each for 90 min with a perfusion rate of 5 ml/min. Perfusion decellularization was observed macroscopically and the decellularized liver matrices were analysed by histology and biochemical analyses (e.g. levels of DNA, glycosaminoglycans and hepatocyte growth factor). Livers decellularized via the hepatic artery and under oscillating pressure showed a more homogeneous decellularization and less remaining DNA, compared with the livers of the other experimental groups. The novel decellularization method described is effective, quick (3 h) and gentle to the extracellular matrix and thus represents an improvement of existing methodology. Copyright © 2014 John Wiley & Sons, Ltd., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background/aim: The indication for resection of cystic pancreatic lesions is usually performed by sectional imaging criteria, such as the Sendai criteria. The aim of this study was to analyze a possible correlation between DNA cytometry and Sendai criteria for the differentiation between low-grade intraductal papillary mucinous neoplasms (IPMN-A) and medium-grade dysplasia (IPMN-B)., Materials and Methods: Histopathological analysis, DNA index and preoperative Sendai criteria were determined in 16 patients who underwent pancreatic resection for IPMN., Results: All patients with IPMN-B showed aneuploid histograms with DNA indices ≥1.3, whereas three out of four patients with IPMN-A had diploid DNA indices ≤1.3. All 11 patients with one or more high-risk stigmata and aneuploid histograms had IPMN-Bs, whereas both patients who were Sendai-negative and diploid in the DNA analysis had an IPMN-A., Conclusion: DNA index may be an important diagnostic tool for the differentiation of different IPMN types beyond the traditional Sendai criteria., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction. Beneath tumor grading and vascular invasion, nontumor related risk factors for HCC recurrence after liver transplantation (LT) have been postulated. Potential factors were analyzed in a large single center experience. Material and Methods. This retrospective analysis included 336 consecutive patients transplanted for HCC. The following factors were analyzed stratified for vascular invasion: immunosuppression, rejection therapy, underlying liver disease, age, gender, blood transfusions, tumor biopsy, caval replacement, waiting time, Child Pugh status, and postoperative complications. Variables with a potential prognostic impact were included in a multivariate analysis. Results. The 5- and 10-year patient survival rates were 70 and 54%. The overall 5-year recurrence rate was 48% with vascular invasion compared to 10% without ( p < 0.001). Univariate analysis stratified for vascular invasion revealed age over 60, pretransplant tumor biopsy, and the application of blood transfusions as significant risk factors for tumor recurrence. Blood transfusions remained the only significant risk factor in the multivariate analysis. Recurrence occurred earlier and more frequently in correlation with the number of applied transfusions. Conclusion. Tumor related risk factors are most important and can be influenced by patient selection. However, it might be helpful to consider nontumor related risk factors, identified in the present study for further optimization of the perioperative management., Competing Interests: The authors declare no conflict of interests.

Purpose: Neuroendocrine tumours of the pancreas (pNET) are observed in 8 - 17 % of patients with von Hippel-Lindau disease (vHLD), and 11 - 20 % of these patients develop metastatic disease. MRI and CT have a very high resolution; however, their sensitivity and specificity for the detection of pNET amongst cystic lesions in the pancreas of vHLD patients are generally considered insufficient. In contrast, (68)Ga-DOTATOC PET/CT demonstrates a high sensitivity for the diagnosis and staging of neuroendocrine tumours. In this study we investigated the potential role of (68)Ga-DOTATOC PET/CT in screening of patients with vHLD., Method: (68)Ga-DOTATOC PET/three-phase contrast-enhanced CT was performed according to guidelines in all consecutive vHLD patients between January 2012 and November 2015. All patients underwent additional MRI imaging of the abdomen, spine, and head. Chromogranin A (CgA) was determined at the time of the PET/CT examination. A lesion seen on (68)Ga-DOTATOC PET in the pancreas was defined as positive if the uptake was visually higher than in the surrounding tissues. Lesions were quantified using maximum SUV., Results: Overall, 20 patients (8 men, 12 women; mean age 44.7 ± 11.1 years) were prospectively examined. Genetically, 12 patients had type 1 vHLD and 8 had type 2 vHLD. (68)Ga-DOTATOC PET/CT detected more pNET than morphological imaging (CT or MRI): 11 patients (55 %; 8 type 1, 3 type 2) vs. 9 patients (45 %; 6 type 1, 3 type 2). The concentration of CgA was mildly elevated in 2 of 11 patients with pNET. The mean SUVmax of the pancreatic lesions was 18.9 ± 21.9 (range 5.0 - 65.6). Four patients (36.4 %) had multiple pNETs. The mean size of the lesions on CT and/or MRI was 10.4 ± 8.3 mm (range 4 - 38 mm), and 41.1 % were larger than 10 mm. In addition, somatostatin receptor-positive cerebellar and spinal haemangioblastomas were detected in three patients (SUVmax 2.1 - 10.1). One patient presented with a solitary somatostatin receptor-positive lymph node metastasis. pNETs were observed more frequently in vHLD type 1 than type 2 (66.7 % vs. 37.5 %, p = 0.089). None of the patients showed progressive disease during follow-up., Conclusion: In this study, (68)Ga-DOTATOC PET detected pNETs in a higher proportion of patients with vHLD than found in previous studies with (111)In-octreoscan, the imaging method recommended by the NCCN. We therefore suggest (68)Ga-DOTATOC PET/CT as the more sensible screening tool.

Liver transplantation has been established as a first-line therapy for a number of indications. Conventional ultrasound and contrast-enhanced ultrasound (CEUS) are methods of choice during the postoperative period as a safe and fast tool to detect potential complications and to enable early intervention if necessary. CEUS increases diagnostic quality and is an appropriate procedure for the examination of vessels and possibly bile ducts. This article presents the state of the art of ultrasound application during the early period after liver transplantation. It addresses common vascular complications and describes the identification of postoperative abnormal findings using ultrasound and CEUS., (© The Foundation Acta Radiologica 2016.)

Purpose: To explore the role of (68)Ga-DOTATATE/DOTATOC PET/CT (SR PET/CT) in patients with suspicion of or histopathologically proven pancreatogenic hyperinsulinaemic hypoglycaemia., Methods: We included 13 patients with histopathologically proven or a high clinical suspicion of pancreatogenic hyperinsulinaemia. All the patients underwent a SR PET/CT scan. The results were correlated with histopathological findings. Normalization of blood glucose levels after resection of the pancreatic lesion, as well as a cytological and/or pathological diagnosis of insulinoma, was considered the diagnostic gold standard for insulinoma. The diagnosis of nesidioblastosis was based on exclusion of an insulinoma and conclusive pathological examination of a segment of the pancreas. Malignant insulinoma was defined as the presence of locoregional or distant metastases., Results: Based on histopathology, 13 patients were found to have pancreatic hyperinsulinaemia: two patients had malignant insulinoma, eight had nonmetastasized insulinoma, and three had nesidioblastosis. SR PET was positive in 11 of the 13 patients (84.6 %) with a final diagnosis of endogenous pancreatic hypoglycaemia. Histopathological staining confirmed 16 foci of hyperinsulinism (insulin positivity). SR PET detected 14 of the 16 lesions, resulting in a sensitivity of 87 %. One intrapancreatic spleen was falsely diagnosed as insulinoma focus on SR PET, resulting in positive predictive value of 93.3 %. Immunohistochemical staining of somatostatin receptor (SSR) subtype 2a was available in ten specimens: two nesidioblastosis, and seven benign and one malignant insulinoma. Eight out of the ten specimens (80 %) stained strongly to moderately positive. Seven of the eight SSR2a-positive lesions were picked up on SR PET. Based on the results of SR PET/CT, nine patients achieved complete remission of the hypoglycaemic events during follow-up., Conclusion: This explorative study suggests that SR PET in combination with CT may play a significant role in the detection and management of patients with pancreatogenic hyperinsulinaemic hypoglycaemia. A large proportion of insulinomas express SSR2a, and a larger study is needed to fully assess the diagnostic accuracy of SR PET in patients with insulinoma and nesidioblastosis compared with current localizing studies used in clinical practice.

Background: Implantable loop recorders (ILRs) allow continuous cardiac monitoring for 3-6 years and are a valuable tool for the investigation of syncopal episodes, palpitations, and atrial fibrillations as well as risk stratification after myocardial infarction. Although magnetic resonance imaging (MRI) in patients with ILRs has been shown to be safe, the impact of ILRs on cardiac MRI image quality has not been investigated yet. Thus, we tested the diagnostic value of cardiac MRI in patients with various types of ILRs., Methods: Two patients with an ILR and a clinical indication to assess myocardial burden of scarring and fibrosis or stress-induced myocardial ischemia underwent cardiac MRI. Device interrogation was performed prior to, immediately after, and 3 months after cardiac MRI., Results: The post-MRI follow-ups revealed no change in programmed ILR parameters, sensing fidelity, and battery parameters. However, ILRs caused significant, uninterpretable hyperintensity artifacts in cardiac MRI., Conclusions: Further clinical studies are warranted to investigate whether modified MRI techniques are helpful to eliminate imaging artifacts., (© 2015 Wiley Periodicals, Inc.)

Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of "borderline resectability". Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future.

Purpose: The aim of this study was to evaluate signs of right-sided heart dysfunction on staging computed tomography (CT) as indirect indicators of carcinoid heart disease., Patients and Methods: Patients with functionally active neuroendocrine neoplasm and different grades of tricuspid valve regurgitation (TR) were identified. Two readers independently reviewed contrast-enhanced staging CT performed within 90 days before or after echocardiography. Logistic regression and receiver operating analyses were used to asses the predictive value of right ventricle-left ventricle ratio (RV-LV ratio), ventricular septal bowing, retrograde contrast filling of the hepatic veins during contrast injection, and time to aortal enhancement greater than 100 Hounsfield units during bolus tracking for TR., Results: Forty-four examinations were evaluated (11 with TR = 0, 16 with TR = 1, 9 with TR = 2, and 8 with TR = 3). Right ventricle-LV ratio was found to predict TR less than or equal to 1 versus TR greater than 1 (P = 0.0188) and TR less than or equal to 1 versus TR equals 2 (P = 0.0082). A prolonged time to aortal enhancement greater than 100 Hounsfield units during bolus tracking predicted TR less than or equal to 1 versus TR greater than 1 (P = 0.0077). Area under the curve for RV-LV ratio was 0.86 when differentiating TR less than or equal to 1 versus TR equals 2. With a cutoff of 1.07, sensitivity was 0.89, and specificity was 0.72., Conclusions: In patients with functionally active neuroendocrine neoplasm, an RV-LV ratio of more than 1.07 predicted TR with a relatively high sensitivity and moderate specificity and thus could serve as an indicator of subclinical carcinoid heart disease on routine staging CT.

Pancreatic neuroendocrine neoplasms (pNEN) are rare malignancies arising from neuroendocrine cells of the pancreas. Functional tumors can present with specific clinical syndromes due to hormonal secretion. These tumors can present as incidental findings on imaging performed for unrelated purposes or they are diagnosed when workup is initiated in patients with specific syndromes or metastases. This article presents an overview of available imaging techniques focusing on computed tomography and magnetic resonance imaging. Recommendations regarding examination protocols are given. Typical imaging features of pNEN and metastases are described. Their potential value for the evaluation of prognosis as well as tumor response under treatment is discussed., (© The Foundation Acta Radiologica 2015.)

Unlabelled: This prospective study compared a 1-d SPECT/CT protocol with the commonly used 3-d protocol for somatostatin receptor scintigraphy in patients with gastroenteropancreatic neuroendocrine neoplasms. Additionally, the influence of SPECT/CT on patient management was evaluated., Methods: From October 2011 to October 2012, all gastroenteropancreatic neuroendocrine neoplasm patients undergoing restaging with somatostatin receptor scintigraphy on a modern SPECT/CT device were enrolled in this study. The protocol consisted of planar imaging at 4, 24, and 48 h; low-dose SPECT/CT at 24 and 48 h; diagnostic CT at 24 h using a triple-phase delay after administration of contrast; and diagnostic SPECT/CT at 24 h. All components of the imaging data were reassessed by 3 masked interpreters. The results were compared with a reference standard based on all clinical, imaging, and histopathology follow-up data available (follow-up range, 24-36 mo; mean, 29.9 mo). The reference standard was defined by a study-specific interdisciplinary tumor board that also reassessed treatment decisions., Results: Thirty-one patients were eligible for analysis (18 men and 13 women; mean age, 60.4 y). Ten had no imaging signs of disease and remained disease-free during follow-up. Twenty-one had persistent or recurrent disease (82 lesions: 24 in the liver, 21 in the lymph nodes, 16 in bone, 12 in the pancreas, and 9 in other locations). The respective lesion detection rates for interpreters 1, 2, and 3 were 51.9%, 49.4%, and 71.6% for low-dose SPECT/CT at 24 h; 51.9%, 55.6%, and 67.9% for low-dose SPECT/CT at 48 h; 63.0%, 70.4%, and 85.2% for diagnostic CT; and 77.8%, 84.0%, and 88.9% for diagnostic SPECT/CT. Interobserver agreement was moderate for diagnostic SPECT/CT (κ = 0.44), diagnostic CT (κ = 0.43), low-dose SPECT/CT at 48 h (κ = 0.61), and low-dose SPECT/CT at 24 h (κ = 0.55). For planar imaging, interobserver agreement was fair after 48 h (κ = 0.36) and 24 h (κ = 0.38) and moderate after 4 h (κ = 0.42). Every lesion detectable on planar imaging or low-dose SPECT/CT was also detectable on diagnostic SPECT/CT. The CT and SPECT components of diagnostic SPECT/CT strongly complemented each other, as 34 of 82 lesions (41.4%) were detected on only the CT component or only the SPECT component. Therapeutic management was influenced by the diagnostic SPECT/CT interpretation in 8 of 31 patients (25.8%)., Conclusion: The highest detection rates were achieved by diagnostic SPECT/CT. Thus, a more patient-friendly 1-d protocol is feasible. Furthermore, multiphase SPECT/CT affected management in about a quarter of patients., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Neuroendocrine neoplasias (NEN) comprise heterogeneous epithelial neoplasms with a large variety of clinical presentations, treatment options and outcomes. Since potentially all NEN bear malignant potential it is important for long-term clinical management and improvement of outcome to decide on successful and oncologically and economically meaningful follow-up strategies. Evidence-based outcome data validating specific follow-up strategies are, however, not available to date and thus outcome data, known prognostic factors and clinical experience guide the decisions on follow-up regimens. The review summarizes general recommendations as well as specific considerations based on tumor entities, clinicopathological tumor characteristics and clinical experience. Follow-up shall serve the patient to improve outcome, benefit from more effective therapies and suffer less from unnecessary and/or toxic therapeutic interventions and finally preserve or gain a good quality of life., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Extrahepatic bile duct injuries remain severe complications during cholecystectomies and often require reconstruction by bilioenteric anastomosis (i.e., hepaticojejunostomy), which comes with further long-term complications (e.g., recurring ascending cholangitis, secondary biliary cirrhosis). In the case of inherent extrahepatic biliary atresia or during liver transplant, artificial or engineered bile ducts could allow novel surgical strategies without the need for hepaticojejunostomy., Methods: We present data on the implantation of in vitro-generated neo-bile ducts in 5 domestic pigs. The neo-bile ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes. On postoperative days 0, 1, 7, and 14, blood samples were taken and analyzed (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, creatinine, and leukocytes). Magnetic resonance cholangiopancreatography was performed on postoperative day 14 on 1 pig. Fourteen days after implantation, the pigs were sacrificed and the bile ducts were explanted., Results: All pigs survived the complete study period without severe complications. None of the pigs showed signs of biliary leakage or peritonitis. The neo-bile ducts were infiltrated by neutrophils, and neoangiogenesis was observed around and into the implanted tissue., Conclusion: We present a novel strategy for extrahepatic bile duct replacement by implantation of an autologous neo-bile duct generated ex vivo. Whether the presented technique allows the long-term replacement of native bile ducts must be further evaluated., (© 2015 S. Karger AG, Basel.)

The currently established standard for planning liver surgery is multistage contrast media-enhanced multidetector computed tomography (CM-CT), which as a rule enables an appropriate resection planning, e.g. a precise identification and localization of primary and secondary liver tumors as well as the anatomical relation to extrahepatic and/or intrahepatic vascular and biliary structures. Furthermore, CM-CT enables the measurement of tumor volume, total liver volume and residual liver volume after resection. Under the condition of normal liver function a residual liver volume of 25 % is nowadays considered sufficient and safe. Recent studies in patients with liver metastases of colorectal cancer showed a clear staging advantage of contrast media-enhanced magnetic resonance imaging (CM-MRI) versus CM-CT. In addition, most recent data showed that the use of liver-specific MRI contrast media further increases the sensitivity and specificity of detection of liver metastases. This imaging technology seems to lead closer to the ideal "one stop shopping" diagnostic tool in preoperative planning of liver resection.

Background: To assess the role of somatostatin receptor (SR) PET/CT using Ga-68 DOTATOC or DOTATATE in staging and restaging of typical (TC) and atypical (AC) lung carcinoids., Methods: Clinical and PET/CT data were retrospectively analyzed in 27 patients referred for staging (N = 5; TC, N = 4; AC, N = 1) or restaging (N = 22; TC, N = 8; AC, N = 14). Maximum standardized uptake value (SUVmax) of SR-positive lesions was normalized to the SUVmax of the liver to generate SUVratio; SR PET was compared to contrast-enhanced (ce) CT. The classification system proposed by Rindi et al. (Endocr Relat Cancer. 2014;21(1):1-16, 2014) was used for classification of patients in TC and AC groups., Results: Only 18/27 patients were found to have metastases on PET/CT. Of the 186 lesions, 101 (54.3 %) were depicted on both PET and CT, 53 (28.5 %) lesions only on CT, and 32 (17.2 %) only on PET. SUVratio of lesions was significantly higher in AC as compared to TC (p < 0.001). In patients referred for restaging, additional findings on PET lead to upstaging with change in management strategy in 5/22 (22.7 %) patients (AC, N = 5; TC, N = 1). In four patients (all AC) referred for restaging and in one patient (TC) referred for staging, additional findings on CT missed on PET lead to correct staging., Conclusions: Typical and atypical carcinoid patients have complex patterns of metastases which make it necessary to combine functional SR PET and contrast-enhanced CT for appropriate restaging. In patients referred for restaging SR, PET may have a relevant impact on treatment strategy in up to 22.7 of patients with typical and atypical lung carcinoids.

Background: Despite novel software solutions, liver volume segmentation is still a time-consuming procedure and often requires further manual optimization. With the high signal intensity of the liver parenchyma in Gd-EOB enhanced magnetic resonance imaging (MRI), liver volume segmentation may be improved., Purpose: To evaluate the practicability of threshold-based segmentation of the liver volume using Gd-EOB-enhanced MRI including a customized three-dimensional (3D) sequence., Material and Methods: A total of 20 patients examined with Gd-EOB MRI (hepatobiliary phase T1-weighted (T1W) 3D sequence [VIBE]; flip angle [FA], 10° and 30°) were enrolled in this retrospective study. The datasets were independently processed by two blinded observers (O1 and O2) in two ways: manual (man) and threshold-based (thresh; study method) segmentation of the liver each followed by an optimization step (man+opt and thresh+opt; man+opt [FA10°] served as reference method). Resulting liver volumes and segmentation times were compared. A liver conversion factor was calculated in percent, describing the non-hepatocellular fraction of the total liver volume, i.e. bile ducts and vessels., Results: Thresh+opt (FA10°) was significantly faster compared to the reference method leading to a median volume overestimation of 4%/8% (P < 0.001). Using thresh+opt (FA30°), segmentation was even faster (P < 0.001) and even reduced median volume deviation of 0%/2% (O1/O2; both P > 0.2). The liver conversion factor was found to be 10%., Conclusion: Threshold-based liver segmentation employing Gd-EOB-enhanced hepatobiliary phase standard T1W 3D sequence is accurate and time-saving. The performance of this approach can be further improved by increasing the FA., (© The Foundation Acta Radiologica 2014.)

Objective: To evaluate whether magnetic resonance imaging (MRI) is effective as computed tomography (CT) in determining morphologic and functional pulmonary changes in patients with cystic fibrosis (CF) in association with multiple clinical parameters., Materials and Methods: Institutional review board approval and patient written informed consent were obtained. In this prospective study, 30 patients with CF (17 men and 13 women; mean (SD) age, 30.2 (9.2) years; range, 19-52 years) were included. Chest CT was acquired by unenhanced low-dose technique for clinical purposes. Lung MRI (1.5 T) comprised T2- and T1-weighted sequences before and after the application of 0.1-mmol·kg gadobutrol, also considering lung perfusion imaging. All CT and MR images were visually evaluated by using 2 different scoring systems: the modified Helbich and the Eichinger scores. Signal intensity of the peribronchial walls and detected mucus on T2-weighted images as well as signal enhancement of the peribronchial walls on contrast-enhanced T1-weighted sequences were additionally assessed on MRI. For the clinical evaluation, the pulmonary exacerbation rate, laboratory, and pulmonary functional parameters were determined., Results: The overall modified Helbich CT score had a mean (SD) of 15.3 (4.8) (range, 3-21) and median of 16.0 (interquartile range [IQR], 6.3). The overall modified Helbich MR score showed slightly, not significantly, lower values (Wilcoxon rank sum test and Student t test; P > 0.05): mean (SD) of 14.3 (4.7) (range, 3-20) and median of 15.0 (IQR, 7.3). Without assessment of perfusion, the overall Eichinger score resulted in the following values for CT vs MR examinations: mean (SD), 20.3 (7.2) (range, 4-31); and median, 21.0 (IQR, 9.5) vs mean (SD), 19.5 (7.1) (range, 4-33); and median, 20.0 (IQR, 9.0). All differences between CT and MR examinations were not significant (Wilcoxon rank sum tests and Student t tests; P > 0.05). In general, the correlations of the CT scores (overall and different imaging parameters) to the clinical parameters were slightly higher compared to the MRI scores. However, if all additional MRI parameters were integrated into the scoring systems, the correlations reached the values of the CT scores. The overall image quality was significantly higher for the CT examinations compared to the MRI sequences., Conclusions: One major diagnostic benefit of lung MRI in CF is the possible acquisition of several different morphologic and functional imaging features without the use of any radiation exposure. Lung MRI shows reliable associations with CT and clinical parameters, which suggests its implementation in CF for routine diagnosis, which would be particularly important in follow-up imaging over the long term.

Unlabelled: Preoperative assessment of liver function and prediction of postoperative functional reserve are important in patients scheduled for liver resection. While determination of absolute liver function currently mostly relies on laboratory tests and clinical scores, postoperative remnant liver function is estimated volumetrically using imaging data obtained with computed tomography (CT) or magnetic resonance imaging (MRI). Accurate estimation of hepatic function is also relevant for intensive care patients, oncologic patients, and patients with diffuse liver disease. The indocyanine green (ICG) test is still the only established test for estimating true global liver function. However, more recent tools such as the LiMAx test also allow global assessment of hepatic function. These tests are limited when liver function is inhomogeneously distributed, which is the case in such conditions as unilateral cholestasis or after portal vein embolization. Imaging-based liver function tests were first developed in nuclear medicine and, compared with laboratory tests, have the advantage of displaying the spatial distribution of liver function. Nuclear medicine scans are obtained using tracers such as 99mTc galactosyl and 99mTc mebrofenin. Liver function is typically assessed using planar scintigraphy. However, three-dimensional volumetry is possible with single-photon emission computed tomography (SPECT-CT). Another technique for image-based liver function estimation is Gd-EOB-enhanced MRI. While metabolization of Gd-EOB in the body is similar to that of ICG and mebrofenin, its distribution in the liver can be displayed by MRI with higher temporal and spatial resolution. Moreover, MRI-based determination of liver function can be integrated into routine preoperative imaging. This makes MRI an ideal candidate for preoperative determination of liver function, though the best pulse sequence and the parameter to be derived from the image information remain to be identified. Another question to be answered is how the results may be affected by renal function and the presence of hyperbilirubinemia. As more results from clinical evaluation including comparison with postoperative liver function data become available, image-based liver function tests, especially with use of Gd-EOB as the contrast medium, have the potential to add another dimension to preoperative imaging., Key Points: Liver function consists of a multitude of subfunctions such as biotransformation, excretion and storage. Global liver function tests are score-based tests such as Child-Pugh or MELD as well as the ICG- and LiMAx-test. Imaging-based liver function tests add spatial information. Current clinical standard is the 99mTc-Mebrofenin-scintigraphy. MRI-based function tests with Gd-EOB-DTPA have the potential to integrate seamlessly into clinical workup, feature a higher temporal and spatial resolution and do not rely on ionizing radiation., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Transarterial chemoembolization (TACE) is established as bridging therapy of HCC listed for transplantation (LT). CT-guided brachytherapy (CTB) has not been evaluated as a bridging concept. We compared CTB and TACE for bridging before LT in HCC patients., Methods: Twelve patients with HCC received LT after CTB (minimal tumour dose, 15-20 Gy). Patients were matched (CTB:TACE, 1:2) by sex, age, number and size of lesions, and underlying liver disease with patients who received TACE before transplantation. Study endpoints were extent of necrosis at histopathology and recurrence rate after OLT., Results: There were no significant differences between the CTB and TACE groups regarding Child-Pugh category (p = 0.732), AFP (0.765), time on waiting list (p = 0.659), number (p = 0.698) and size (p = 0.853) of HCC lesions, fulfilment of Milan-criteria (p = 0.638), or previous liver-specific treatments. CTB achieved higher tumour necrosis rates than TACE (p = 0.018). The 1- and 3-year recurrence rate in the CTB group was 10 and 10 % vs. TACE, 14 and 30 % (p = 0.292)., Conclusions: Our data show comparable or even better response and post-LT recurrence rates of CTB compared to TACE for treating HCC in patients prior to LT. CTB should be further evaluated as an alternative bridging modality, especially for patients not suited for TACE., Key Points: • CT-guided interstitial brachytherapy (CTB) is a promising alternative to transarterial chemoembolization (TACE). • CTB instead of TACE is possible for bridging to liver transplantation in HCC patients. • HCC recurrence was not associated with CTB despite potential tumour seeding.

Objectives: Pancreatoduodenectomy is feasible also in patients with locally advanced pancreatic adenocarcinoma (PA) nowadays. Data on risk and survival analysis of palliative pancreatic resections followed by gemcitabine-based chemotherapy (Cx) are limited., Methods: Between 2000 and 2009, a total of 45 patients had primary cytoreductive surgery (cS) (pancreaticoduodenectomy or total pancreatectomy) followed by gemcitabine-based Cx (cS + Cx) for advanced PA. We matched 1:1 the cS + Cx group with 45 contemporaneous patients who primarily started palliative gemcitabine-based Cx for age, sex, performance status, and body mass index. Overall, survival was evaluated., Results: Local R0 and R1 resection in metastatic patients was achieved in 27% and 27%, respectively. The R2 resection status without distant metastasis resulted in 33%, whereas 13% showed a local R2 status with additional metastasis (M1). Median overall survival was 10.4 months after cytoreductive pancreatic surgery and consecutive gemcitabine-based Cx versus 7.2 months after upfront gemcitabine-based Cx (P = 0.009). Median survival for R0/M1 patients was 14.4 months and 11.0 months for R2/M0 patients, whereas the median survival for R1/M1 and for R2/M1 patients was 7.3 months and 6.1 months, respectively., Conclusions: Individual patients with advanced PA had a significantly longer overall survival after palliative pancreaticoduodenectomy followed by Cx than patients in a matched control group who underwent primarily palliative Cx.

Objective: To investigate whether dose reduction via adaptive statistical iterative reconstruction (ASIR) affects image quality and diagnostic accuracy in neuroendocrine tumor (NET) staging., Methods: A total of 28 NET patients were enrolled in the study. Inclusion criteria were histologically proven NET and visible tumor in abdominal computed tomography (CT). In an intraindividual study design, the patients underwent a baseline CT (filtered back projection, FBP) and follow-up CT (ASIR 40%) using matched scan parameters. Image quality was assessed subjectively using a 5-grade scoring system and objectively by determining signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNRs). Applied volume computed tomography dose index (CTDIvol) of each scan was taken from the dose report., Results: ASIR 40% significantly reduced CTDIvol (10.17±3.06mGy [FBP], 6.34±2.25mGy [ASIR] (p<0.001) by 37.6% and significantly increased CNRs (complete tumor-to-liver, 2.76±1.87 [FBP], 3.2±2.32 [ASIR]) (p<0.05) (complete tumor-to-muscle, 2.74±2.67 [FBP], 4.31±4.61 [ASIR]) (p<0.05) compared to FBP. Subjective scoring revealed no significant changes for diagnostic confidence (5.0±0 [FBP], 5.0±0 [ASIR]), visibility of suspicious lesion (4.8±0.5 [FBP], 4.8±0.5 [ASIR]) and artifacts (5.0±0 [FBP], 5.0±0 [ASIR]). ASIR 40% significantly decreased scores for noise (4.3±0.6 [FBP], 4.0±0.8 [ASIR]) (p<0.05), contrast (4.4±0.6 [FBP], 4.1±0.8 [ASIR]) (p<0.001) and visibility of small structures (4.5±0.7 [FBP], 4.3±0.8 [ASIR]) (p<0.001)., Conclusion: In clinical practice ASIR can be used to reduce radiation dose without sacrificing image quality and diagnostic confidence in staging CT of NET patients. This may be beneficial for patients with frequent follow-up and significant cumulative radiation exposure., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Postoperative bile leaks represent a typical complication in liver surgery with a frequency ranging from 5 % to 12 % in large series. The treatment of choice is usually conservative. Using sufficient transcutaneous drainage with flushing of the biloma cavity and endoscopic retrograde cholangiography (ERC) with sphincterotomy and possibly stenting, the cure rate of bile leaks is approximately 95 %. In very rare cases all of these measures remain unsuccessful especially in cases of leakage from separated liver segments without connection to the main bile duct system. In relevantly separated liver segments this can lead to a chronically secreting bile fistula.We report a series of seven patients after complex liver resections, in which a chronic bile cavity was definitively treated with a jejunum loop as internal drainage. The prior conservative therapy included cavity suction drainage and optionally an additional ERC with or without stent insertion. After several weeks of bile leak persistence and radiological confirmation of suturable bile wall the operative treatment was carried out. The biloma cavity was careful dissected, opened and anastomosed with a jejunal loop. The further postoperative course was uncomplicated in all patients.It is possible to treat chronic persistent bile leaks safely and effectively by internal drainage through the jejunal loop after formation of a suturable biloma cavity membrane.

Background: The role of systemic chemotherapy for pancreatic neuroendocrine tumours (pNET) is controversially discussed. Objective response rates (RR) reported for streptozocin (STZ)-based chemotherapy are variable and novel targeted drugs have recently been approved. However, the sequence of treatment remains unclear. We aimed to evaluate the efficacy of STZ plus 5-fluorouracil (STZ/5-FU) in a large pNET cohort., Methods: Data from 96 pNET patients treated with STZ/5-FU were analysed retrospectively. Endpoints of the study were RR, time to tumour progression (TTP) and overall survival (OS)., Results: Mean age of patients at the start of chemotherapy was 57.6years (range, 32.1-80.4). STZ/5-FU was the 1st line treatment in 56.3%. 11.5% had G1, 79.2% G2 and 6.3% G3 neoplasms. Baseline progression was evident in 74%. Objective response rate was 42.7%. 40.6% of patients showed stable disease as best response while 16.7% showed progressive disease. Treatment was discontinued due to toxicity in 16 patients. Median TTP and OS were 19.4 (95% confidence interval (CI), 13.6-25.2) and 54.8months (95% CI, 34.7-74.9), respectively. In Cox regression analysis, Ki67>15% was the only negative prognostic factor for TTP (hazard ratio (HR), 3.3; P<0.001), confirmed by multivariate analysis (HR, 6.7; P=0.001)., Conclusions: STZ/5-FU was associated with considerable RR. Treatment was associated with durable TTP especially in patients with Ki67-index of ⩽15%. These findings along with good tolerability strengthen the value of this two-drug chemotherapy for the management of unresectable pNET., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Advanced pancreatic cancer (APC), in addition to its high mortality, accounts for the highest rates of venous thromboembolic events (VTEs). Enoxaparin, a low-molecular weight heparin, is effective in prevention and treatment of VTEs. Some small studies have indicated that this benefit might extend to patients with cancer., Patients and Methods: Patients with histologically proven APC were randomly assigned to ambulant first-line chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to investigate the probable reduction in symptomatic VTEs and the impact on survival., Results: A total of 312 patients were recruited as one of the protocol end points was reached. Within the first 3 months, the numbers of symptomatic VTEs were as follows: 15 of 152 patients in the observation group and two of 160 patients in the enoxaparin group (hazard ratio [HR], 0.12; 95% CI, 0.03 to 0.52; χ(2) P = .001). The numbers of major bleeding events were as follows: five of 152 patients in the observation arm and seven of 160 patients in the enoxaparin arm (HR, 1.4; 95% CI, 0.35 to 3.72; χ(2) P = 1.0). Overall cumulative incidence rates of symptomatic VTEs were 15.1% (observation) and 6.4% (enoxaparin; HR, 0.40; 95% CI, 0.19 to 0.83; P = .01). Progression-free (HR, 1.06; 95% CI, 0.84 to 1.32; P = .64) and overall survival (HR, 1.01; 95% CI, 0.87 to 1.38; P = .44) did not differ between groups., Conclusion: This study demonstrates the high efficacy and feasibility of primary pharmacologic prevention of symptomatic VTEs in outpatients with APC. Treatment efficacy was not affected by simultaneous treatment with enoxaparin in this trial setting., (© 2015 by American Society of Clinical Oncology.)

Objectives: Evaluation of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiation of pancreatic intraductal papillary mucinous neoplasm (IPMN) subtypes based on objective imaging criteria., Methods: Fifty-eight patients with 60 histologically confirmed IPMNs were included in this retrospective study. Eighty-three imaging studies (CT,n = 42; MRI,n = 41) were analysed by three independent blinded observers (O1-O3), using established imaging criteria to assess likelihood of malignancy (-5, very likely benign; 5, very likely malignant) and histological subtype (i.e., low-grade (LGD), moderate-grade (MGD), high-grade dysplasia (HGD), early invasive carcinoma (IPMC), solid carcinoma (CA) arising from IPMN)., Results: Forty-one benign (LGD IPMN,n = 20; MGD IPMN,n = 21) and 19 malignant (HGD IPMN,n = 3; IPMC,n = 6; solid CA,n = 10) IPMNs located in the main duct (n = 6), branch duct (n = 37), or both (n = 17) were evaluated. Overall accuracy of differentiation between benign and malignant IPMNs was 86/92 % (CT/MRI). Exclusion of overtly malignant cases (solid CA) resulted in overall accuracy of 83/90 % (CT/MRI). The presence of mural nodules and ductal lesion size ≥30 mm were significant indicators of malignancy (p = 0.02 and p < 0.001, respectively)., Conclusions: Invasive IPMN can be identified with high confidence and sensitivity using CT and MRI. The diagnostic problem that remains is the accurate radiological differentiation of premalignant and non-invasive subtypes., Key Points: • CT and MRI can differentiate benign from malignant forms of IPMN. • Identifying (pre)malignant histological IPMN subtypes by CT and MRI is difficult. • Overall, diagnostic performance with MRI was slightly (not significantly) superior to CT.

Objectives: To compare Gd-EOB-enhanced MRI and (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests for separate evaluation of right (RLL) and left liver lobe (LLL) function., Methods: Fourteen patients underwent Gd-EOB-enhanced MRI and (99m)Tc-mebrofenin HBS after portal vein embolization within 24 h. Relative enhancement (RE) and hepatic uptake index (HUI) were determined from MRI; and T max, T 1/2 and mebrofenin uptake were determined from HBS, all values separately for RLL and LLL., Results: Mebrofenin uptake correlated significantly with HUI and RE for both liver lobes. There was strong correlation of mebrofenin uptake with HUI for RLL (r (2) = 0.802, p = 0.001) and RE for LLL (r (2) = 0.704, p = 0.005) and moderate correlation with HUI for LLL (r (2) = 0.560, p = 0.037) and RE for RLL (r (2) = 0.620, p = 0.018). Correlating the percentage share of RLL function derived from MRI (with HUI) with the percentage of RLL function derived from mebrofenin uptake revealed a strong correlation (r (2) = 0.775, p = 0.002)., Conclusions: Both RE and HUI correlate with mebrofenin uptake in HBS. The results suggest that Gd-EOB-enhanced MRI and (99m)Tc-mebrofenin HBS may equally be used to separately determine right and left liver lobe function., Key Points: • Information about liver function can be acquired with routine Gd-EOB-MRI. • Gd-EOB-MRI and (99m) Tc-mebrofenin HBS show elevated function of non-embolized lobe. • Gd-EOB-MRI and (99m) Tc-mebrofenin HBS can determine lobar liver function.

Purpose: The purpose of the present study was to evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) in patients with unresectable hepatocellular carcinoma (HCC)., Patients and Methods: Over a 6-year period, 98 patients with 212 unresectable HCC underwent CT-HDRBT applying a (192)Ir source at our institution. Magnetic resonance imaging (MRI) follow-up was performed 6 weeks after the intervention and then every 3 months. The primary endpoint was local tumor control (LTC); secondary endpoints included progression-free survival (PFS) and overall survival (OS)., Results: Patients were available for MRI evaluation for a mean follow-up of 23.1 months (range 4-64 months; median 20 months). Mean tumor diameter was 5 cm (range 1.8-12 cm). Eighteen of 212 (8.5 %) tumors showed local progression after a mean LTC of 21.1 months. In all, 67 patients (68.4 %) experienced distant tumor progression. The mean PFS was 15.2 months. Forty-six patients died during the follow-up period. Median OS was 29.2 months. Actuarial 1-, 2-, and 3-year OS rates were 80, 62, and 46 %, respectively., Conclusion: CT-HDRBT is an effective therapy to attain local tumor control in patients with unresectable HCC. Prospective randomized studies comparing CT-HDRBT with the standard treatments like Radiofrequency ablation (RFA) and chemoembolization (TACE) are mandatory.

Autoimmune pancreatitis is a rare type of chronic pancreatitis. It is supposed to be a pancreatic manifestation of an immune-complex modulated systemic disorder. In contrast, pancreatic adenocarcinoma is the most frequent malignant neoplasm of the pancreas. Within the rare type of focal autoimmune pancreatitis, only few presentations with multifocal pancreatic lesions have been described. Herein we report a case of a 58-year-old patient with autoimmune pancreatitis presenting with bifocal manifestations of the pancreatic head and tail, mimicking pancreatic adenocarcinoma clinically, on computed tomography and magnetic resonance imaging. Typical imaging findings of autoimmune pancreatitis are compared with typical findings in pancreatic carcinoma. The diagnostic dilemma of differentiating between both entities is discussed. A review of the present literature regarding multifocal presence of autoimmune pancreatitis is performed.

Background: Portal vein embolization (PVE) has become the standard of care before extended hepatectomy. Various PVE methods using different embolization materials have been described. In this study, we compared PVE with polyvinyl alcohol particles alone (PVA only) versus PVA with plug or coils (PVA + plug/coils)., Materials and Methods: Patients undergoing PVE before hepatectomy were included. PVA alone was used until December 2013, thereafter plug or coils were placed in addition. The volume of left lateral liver lobe (LLL), clinical parameters, and liver function tests were measured before PVE and resection., Results: A total of 43 patients were recruited into the PVA only group and 42 were recruited into the PVA + plug/coils group. There were no major differences between groups except significantly higher total bilirubin level before PVE in the PVA only group, which improved before hepatectomy. Mean LLL volume increased by 25.7% after PVE in the PVA only group and by 44% in the PVA + plug/coils group (P < 0.001). Recanalization was significantly less common in the PVA + plug/coils group. In multivariate regression, initial LLL volume and use of plug or coils were the only parameters influencing LLL volume increase. The postoperative liver failure rate was significantly reduced in PVA + plug/coils group (P = <0.001)., Conclusions: PVE using PVA particles together with plug or coils is a safe and efficient method to increase future liver remnant volume. The additional central embolization with plug or coils led to an increased hypertrophy, due to lower recanalization rates, and subsequently decreased incidence of postoperative liver failure. No additional procedure-specific complications were observed in this series., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Portal vein embolization (PVE) before extended right hepatectomy leads to an increase of the future liver remnant (FLR) volume, but predictive factors for sufficient hypertrophy are still unclear. The purpose of this study was to investigate parameters influencing the growth of FLR., Methods: Patients undergoing PVE prior hepatic resection were evaluated. PVE was done using polyvinyl alcohol particles only. Volumetric analysis was performed before embolization and before hepatectomy. Success of PVE was determined as percental growth of the future liver remnant., Results: Seventy-seven patients were included, and three cohorts were formed according to the hypertrophy of FLR. FLR increased from 448.2 ± 187 to 475.5 ± 191 in the poor, from 315.3 ± 86 to 469.1 ± 142 in the moderate, and from 283.4 ± 68 to 400.4 ± 110 in the good hypertrophy group. More cases of recanalization of the portal vein were observed in patients with poor hypertrophy (p = 0.016). Small FLR before PVE predict higher growth of the FLR (p = 0.006). Duration between PVE and surgery differed significantly: 22 (poor) vs. 32 (good) days (p = 0.040)., Discussion: No recanalization, small initial FLR and longer time were assessed with better FLR hypertrophy. More sufficient PVE techniques and postponed hepatectomy might improve the outcome. Small initial FLR should not be a disclosure for curative hepatectomy.

Background: Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are not considered for liver transplantation (LT) in many centres; however, LT may be the only treatment able to achieve long-term survival in patients with unresectable HCC. The aim of this study was to assess the role of recipient age and tumour biology expressed by the DNA index in the selection of HCC patients for LT., Patients: Clinicopathological data of 364 patients with HCC who underwent LT between 1989 and 2010 were evaluated. Overall survival (OS) was analysed by patient age, tumour burden based on Milan criteria and the DNA index., Results: After a median follow-up time of 78 months, the median survival was 100 months. Factors associated with OS on univariate analysis included Milan criteria, patient age, hepatitis C infection, alpha-fetoprotein (AFP) level, the DNA index, number of HCC, diameter of HCC, bilobar HCC, microvascular tumour invasion and tumour grading. On multivariate analysis, HCC beyond Milan criteria and the DNA index >1.5 independently predicted a worse OS. When stratifying patients by both age and Milan criteria, patients ≤ 60 years with HCC beyond Milan criteria had an OS comparable to that of patients >60 years within Milan criteria (10-year OS: 33% versus 37%, P = 0.08). Patients ≤ 60 years with HCC beyond Milan criteria but a favourable DNA index ≤ 1.5 achieved excellent long-term outcomes, comparable with those of patients within Milan criteria., Conclusions: Patients ≤ 60 years may undergo LT for HCC with favourable outcomes independently of their tumour burden. Additional assessment of tumour biology, e.g. using the DNA index, especially in this subgroup of patients can support the selection of LT candidates who may derive the most long-term survival benefit, even if Milan criteria are not fulfilled., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background or Purpose: Computed tomography-guided high-dose-rate brachytherapy (CT-HDRBT) is an emerging therapeutic option for irresectable liver tumours. However, its potentially negative effect on liver function has not yet been investigated. The aim of this study was to evaluate CT-HDRBT for potential liver damage and functional impairment by means of quantitative liver function tests, patient safety, and survival., Methods: Sixty-nine patients receiving hepatic CT-HDRBT were investigated in a prospective study. The liver function was determined before and after intervention, and 6 and 12 weeks later. The study visits included liver function assessment by conventional biochemical parameters, the liver function capacity test based on 13C-Methacetin (MA) kinetics in µg/kg/hr (LiMAx test), and the indocyanine green plasma disappearance rate test. Tumour progression was re-staged by magnetic resonance imaging (MRI) twice. The 2-year-survival was analysed., Results: A significant alteration of biochemical liver parameters was observed for liver enzymes and bilirubin directly after intervention, all biochemical parameters had normalised at the 6-week follow-up. There were no changes in LiMAx test values after the intervention, showing no effect on metabolic liver function capacity. In approximately two-thirds of the patients, MRI re-staging revealed a significant tumour response, and no local tumour recurrence occurred. No patient developed a radiation-induced liver disease., Conclusion: CT-HDRBT for local tumour treatment has little impact on total liver function capacity by high patient safety and encouraging survival rates. Thus, it should be an important option in treating patients without a surgical alternative, especially when liver function is impaired due to previous surgery or chronic liver disease.

Background: The role of hepatectomy for patients with liver metastases from gastric and esophageal cancer (GELM) is not well defined. The present study examined the morbidity, mortality, and long-term survivals after liver resection for GELM., Methods: Clinicopathological data of patients who underwent hepatectomy for GELM between 1995 and 2012 at two European high-volume hepatobiliary centers were assessed, and predictors of overall survival (OS) were identified. In addition, the impact of preoperative chemotherapy for GELM on OS was evaluated., Results: Forty-seven patients underwent hepatectomy for GELM. The primary tumor was located in the stomach, cardia, and distal esophagus in 27, 16, and 4 cases, respectively. Twenty patients received preoperative chemotherapy before hepatectomy. After a median follow-up time of 76 months, 1-, 3-, and 5-year OS rates were 70, 37, and 24%, respectively. Postoperative morbidity and mortality rates were 32 and 4%, respectively. Outcomes were comparable between the two centers. Preoperative chemotherapy for GELM (5-year OS: 45 vs 9%, P = .005) and the lack of posthepatectomy complications (5-year OS: 34 vs 0%, P < .0001) were significantly associated with improved OS in univariate and multivariate analyses. When stratifying OS by radiologic response of GELM to preoperative chemotherapy, patients with progressive disease despite preoperative treatment had significantly worse OS (5-year OS: 0 vs 70%, P = .045)., Conclusion: For selected patients with GELM, liver resection is safe and should be regarded as a potentially curative approach. A multimodal treatment strategy including systemic therapy may provide better patient selection resulting in prolonged survival in patients with GELM undergoing hepatectomy.

Objective: To correctly display the left and right liver lobe separately on dynamic projection scintigraphy, it is essential to adjust the collimator to the angle of the plane between the two liver lobes. We propose an optimized protocol for separating left and right liver lobe in (99m)Tc-mebrofenin hepatobiliary scintigraphy in a hybrid SPECT-CT device. The protocol uses the inherent attenuation correction low-dose CT (AC-CT) for individually adjusting gamma camera head angulation. The results of this protocol are compared with hypothetical results based on previous MRI, fixed angle, and traditional frontal projection., Methods: The absolute and relative degrees of overlapping volume between left and right liver lobe parenchyma for frontal projection, 45° right anterior oblique (RAO) projection, RAO angulation based on previously acquired MRI, and RAO based on the AC-CT were measured in 14 patients who underwent (99m)Tc-mebrofenin hepatobiliary scintigraphy., Results: Relative degree of overlap was 31.3 ± 15.2 % for frontal projection, 8.2 ± 6.5 % for 45° RAO, 5.5 ± 3.5 % for RAO based on previous MRI, and 3.6 ± 2.5 % for RAO based on AC-CT. The relative overlap of RAO projections based on previous MRI was significantly lower than for frontal projection (p < 0.05). Use of the angle from the prior AC-CT, however, resulted in an even lower degree of overlap (p < 0.05)., Conclusions: Performing (99m)Tc-mebrofenin hepatobiliary scintigraphy using RAO detector alignment with an angle derived from a prior CT obtained in the SPECT-CT scanner can significantly reduce the degree of overlap between right and left liver lobe. If SPECT-CT is not available, previous CT or MRI or a fixed angle of 45° may be used.

Purpose: To retrospectively analyze efficacy as measured by volume gain of future remnant liver (FRL) after right portal vein embolization (PVE) using particles only versus particles and additional central plug and/or coil (CP/C) embolization., Methods: All patients who underwent PVE between July 2011 and December 2012 were retrospectively analyzed. Right PVE was performed either with particle-only (PO) embolization or additional CP/C embolization. All enrolled patients underwent computed tomography or magnetic resonance imaging before PVE and surgery. The images were used for volumetry of the FRL., Results: Of 75 patients, 40 had PO and 35 CP/C embolization. Age, sex, and tumor entities did not differ significantly between the two groups. Tumor entities included cholangiocarcinoma (n = 52), metastasis from colorectal cancer (n = 14), hepatocellular carcinoma (n = 2), and others (n = 7). Time from PVE to preoperative imaging was similar in both groups. FRL volume before PVE was 329 ± 121 ml in the PO group and 333 ± 135 ml in the CP/C group, and 419 ± 135 ml and 492 ± 165 ml before operation. The average percentage volume gain was significantly higher in the CP/C group than in the PO group, with 53.3 ± 34.5 % versus 30.9 ± 28.8 % (p = 0.002)., Conclusion: Right PVE with additional CP/C embolization leads to a significantly higher gain in FRL volume than embolization with particles alone.

Objectives: To estimate the additional value of an increased flip angle of 35° in late phase Gd-EOB-DTPA-enhanced magnetic resonance cholangiography, as compared to T2w-MRCP., Methods: 40 adult patients underwent Gd-EOB-DTPA enhanced MRI of the liver including a T2-weighted 3D TSE MRCP (T2w-MRCP) as well as a late phase T1-weighted THRIVE sequences applying a flip angle of 35° (fa35). Two experienced observers evaluated the images regarding the delineation of the different biliary regions using a three-point grading system. A five-point scale was applied to determine the readers' confidence in identifying anatomical variations of the biliary tree. ROI analysis was performed to compare the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios., Results: The quality for visualizing the biliary tree differed between T2w-MRCP and fa35 (p=<0.001). Late phase EOB-MRC was rated as good for delineating the entire biliary system, whereas T2w-MRCP received an overall poor rating. Especially the depiction of the intrahepatic bile ducts was estimated as problematic in T2w-MRCP. T2w-MRCP and fa35 revealed a discordant assessment of anatomical variations in 12.5% of the cases, comprising a generally higher confidence level for fa35 (4.0 ± 1.1 vs. 2.2 ± 1.2, p=<0.001). SNR proofed to be significantly higher in fa35 (p=<0.001), whereas T2w-MRCP revealed a significantly higher CNR (<0.001)., Conclusions: Gd-EOB-DTPA enhanced magnetic resonance cholangiography acquired with a flip angle of 35° revealed a better diagnostic performance compared to T2w-MRCP and might be a valuable adjunct in assessing functional bile duct abnormalities., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Inflammatory myofibroblastic tumors (IMT) are a benign tumor entity, which rarely develop in the liver. Surgery is the most common treatment for these lesions as it is difficult to distinguish them from malignant liver tumors and local recurrent growth may occur. IMT is a diagnostic challenge for imaging. Only a limited number of reports of single cases or small number of patients described the imaging features on computed tomography. Reports on IMT appearance on magnetic resonance imaging are scarce. We present a case of IMT of the liver with infiltration of the abdominal wall treated with surgery and describe the imaging features with the use of the hepatobiliary contrast agent, gadoxetic acid (Gd-EOB).

Aim: To retrospectively evaluate infectious hepatic complications of transarterial radioembolization (RE) of the liver in patients with pre-existing biliodigestive anastomosis., Patients and Methods: Patients who underwent RE were retrospectively analyzed. All patients had at least a contrast-enhanced magnetic resonance imaging or contrast-enhanced triple-phase computed tomographic scan before and 6-8 weeks after RE., Results: Overall, 143 patients (67 women, 76 men; median age = 65 ± 11.2 years) were analyzed. Nine patients had a biliodigestive anastomosis. The complications were as follows: one case of cholecystitis, three of gastroduodenal ulcer with one ulcer perforation, and six of radioembolization-induced liver disease. There were no infectious complications. There were no major or minor complications in the group with previous biliodigestive anastomosis., Conclusion: Pre-existing bilioenteric anastomoses are not a negative predictive factor for the development of infectious hepatic complications after RE. RE with (90)Y microspheres can be safely performed following careful patient selection., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: To evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) of unresectable colorectal liver metastases (CRLMs)., Materials and Methods: Retrospective analysis of all consecutive patients with unresectable CRLMs treated with CT-HDRBT between January 2008 and November 2012. Treatment was performed by CT-guided catheter placement and high-dose-rate brachytherapy with an iridium-192 source. MRI follow-up was performed after 6 weeks and then every 3 months post-intervention. The primary endpoint was local tumor control (LTC); secondary endpoints included time to progression (TTP) and overall survival (OS)., Results: 80 heavily pretreated patients with 179 metastases were available for MRI evaluation for a mean follow-up time of 16.9 months. The mean tumor diameter was 28.5 mm (range: 8 - 107 mm). No major complications were observed. A total of 23 (12.9 %) local tumor progressions were observed. Lesions ≥ 4 cm in diameter showed significantly more local progression than smaller lesions (< 4 cm). 50 patients (62.5 %) experienced systemic tumor progression. The median TTP was 6 months. 28 (43 %) patients died during the follow-up period. The median OS after ablation was 18 months., Conclusion: CT-HDRBT is an effective technique for the treatment of unresectable CRLMs and warrants promising LTC rates compared to thermal ablative techniques. A combination with other local and systemic therapies should be evaluated in patients with lesions > 4 cm in diameter, in which higher progression rates are expected., Key Points: • CT-HDRBT enables a highly cytotoxic irradiation of colorectal liver metastases with simultaneous conservation of important neighboring structures (eg liver parenchyma, bile ducts and bowel)• The local tumor control rates obtained by CT-HDRBT in patients with colorectal liver metastases are promising, also compared to the local tumor control rates after RFA• Metastases with a diameter of 4 cm or abow, display a higher local progression rate after CT-HDRBT, therefor a combination therapy with other locoregional or systemic treatments should be investigated in prospective studies., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Evaluation of enhancement characteristics of histopathologically confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs) with gadoxetic acid-enhanced MRI., Methods: Sixty-eight patients with 115 histopathologically proven lesions (FNHs, n=44; HCAs, n=71) examined with gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference: surgical resection, n=53 patients (lesions: FNHs, n=37; HCAs, n=53); biopsy, n=15 (lesions: FNHs, n=7; HCAs, n=18)). Two radiologists evaluated all MR images regarding morphological features as well as the vascular and hepatocyte-specific enhancement in consensus., Results: For the hepatobiliary phase, relative enhancement of the lesions and lesion to liver enhancement were significantly lower for HCAs (mean, 48.7 (±48.4)%and 49.4 (±33.9) %) compared to FNHs (159.3 (±92.5) %; and 151.7 (±79) %; accuracy of 89%and 90 %, respectively; P<0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior to all other morphological and dynamic vascular criteria alone and in combination (accuracy, 54–85 %)., Conclusions: For differentiation of FNHs and HCAs by means of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior to all other criteria alone and in combination., Key Points: EOB-MRI is well suited to differentiate FNHs and hepatocellular adenomas. For this purpose hepatobiliary phase is superior to unenhanced and dynamic imaging. Hepatobiliary phase (peripheral) hyper- or isointensity is typical for FNH. Hepatobiliary phase hypointensity is typical for hepatocellular adenomas. EOB-MRI helps to avoid misinterpretations of benign hepatocellular lesions.

Background: This multicentre international randomized trial compared the impact of gadoxetic acid-enhanced magnetic resonance imaging (MRI), MRI with extracellular contrast medium (ECCM-MRI) and contrast-enhanced computed tomography (CE-CT) as a first-line imaging method in patients with suspected colorectal cancer liver metastases (CRCLM)., Methods: Between October 2008 and September 2010, patients with suspected CRCLM were randomized to one of the three imaging modalities. The primary endpoint was the proportion of patients for whom further imaging after initial imaging was required for a confident diagnosis. Secondary variables included confidence in the therapeutic decision, intraoperative deviations from the initial imaging-based surgical plan as a result of additional operative findings, and diagnostic efficacy of the imaging modalities versus intraoperative and pathological extent of the disease., Results: A total of 360 patients were enrolled. Efficacy was analysed in 342 patients (118, 112 and 112 with gadoxetic acid-enhanced MRI, ECCM-MRI and CE-CT respectively as the initial imaging procedure). Further imaging was required in 0 of 118, 19 (17.0 per cent) of 112 and 44 (39.3 per cent) of 112 patients respectively (P < 0.001). Diagnostic confidence was high or very high in 98.3 per cent of patients for gadoxetic acid-enhanced MRI, 85.7 per cent for ECCM-MRI and 65.2 per cent for CE-CT. Surgical plans were changed during surgery in 28, 32 and 47 per cent of patients in the respective groups., Conclusion: The diagnostic performance of gadoxetic acid-enhanced MRI was better than that of CE-CT and ECCM-MRI as the initial imaging modality. No further imaging was needed in the gadoxetic acid-enhanced MRI group and comparison of diagnostic efficacy parameters demonstrated the diagnostic superiority of gadoxetic acid-enhanced MRI., Registration Number: NCT00764621(http://clinicaltrials.gov); EudraCT number: 2008-000583-16 (https://eudract.ema.europa.eu/)., (© 2014 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Introduction: Local ablative treatments play an important role in current surgical treatment strategies. Radiofrequency ablation (RFA) as one of the most popular examples suffers from partly inacceptable local tumour control. Microwave coagulation therapy (MCT) is a comparatively new type of ablation promising several improvements. This series is to the best of our knowledge the first within the central European area, which reports on the successful clinical implementation of MCT in a surgical department., Patients and Materials: A novel 915 MHz system (MedWaves™, AveCure Inc., SanDiego, CA/U. S. A.) was used to treat 47 patients with 80 tumour nodules in 51 treatment sessions. Average tumour size was 2.6 ± 0.9 cm. Indications were hepatocellular carcinoma in 29 patients and metastases in 14 as well as 4 cholangiocellular carcinomas. The approach was laparoscopic (20) or percutaneous (31). High-risk conditions defined by unfavourable tumour localisation like invisibility in native transabdominal ultrasound, superficial tumour site or risk of heat sink phenomena were found in 28 cases (53 %)., Results: Local recurrence rate was 17 % on a per-patient and 12 % on a per-tumour basis (n = 9). One patient died because of incurable upper gastrointestinal bleeding during the postoperative hospital stay. No MCT-associated complication occurred. Median follow-up period was 20 months. Local tumour recurrence was significantly different on comparing laparoscopic to percutaneous MCT (p = 0.032, χ2 test), as was global recurrence (p = 0.011, χ2 test). In a univariate logistic Cox regression, tumour size, access and high-risk localisation were significant prognostic factors for local tumour recurrence, however, in a multivariate reiteration, only the chosen access to MCT (p = 0.012) and tumour size (p = 0.044) remain significant., Conclusion: MCT seems to be a useful tool, easy to implement in a surgical environment and may eventually prove to be superior to other local ablative treatment modalities. Even unfavourable tumour localisations could be treated safely and efficiently using MCT without increased risk of local tumour recurrence., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To retrospectively analyze the degree of artefacts in CT and MRI scans caused by coils and vascular plugs used for portal vein embolization (PVE)., Materials and Methods: All patients who underwent PVE between July 2011 and December 2012 and received either plug or coil embolization additional to particle embolization were retrospectively analyzed. Artefacts causes by embolization materials were measured in CT and MRI scans following PVE., Results: The sum of the artefact diameters caused from coils was significantly higher in CT (188.3 ± 26.1 mm) than in MRI T1 (50.5 ± 6.5 mm) or T2 imaging (39.5 ± 9.7 mm) (P<0.05). In MRI, the diameter in T1 and T2 sequences did not differ significantly (P=0.977). The sum of the artefact diameters from vascular plugs in MRI T1 sequences (62.5 ± 8.7 mm) was significantly higher than in CT (46.6 ± 4.8 mm; P<0.05) and MRI T2 sequences (52.8 ± 3.8 mm; P<0.05)., Conclusion: PVE with particles and vascular plug causes significantly fewer artefacts than PVE with particles and coils on CT scans following embolization, which can be important in the event of vascular complications or in follow-up scans, should the patient become unresectable., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The optimal sequence for Gd-EOB-DTPA uptake measurement in the liver with the purpose of liver function measurement is still not defined., Purpose: To prospectively evaluate the effect of an increased flip angle (FA) of a T1-weighted fat-saturated 3D sequence for the measurement of hepatocyte uptake of Gd-EOB-DTPA magnetic resonance imaging (MRI) after right portal vein embolization (PVE)., Material and Methods: Ten patients who received a PVE prior to an extended hemihepatectomy were examined 14 days after PVE using Gd-EOB-DTPA enhanced MRI of the liver using the standard FA of 10° and the increased FA of 30°., Results: Relative enhancement of the right liver lobe (RLL) was 0.52 ± 0.12 for 10° and 1.41 ± 0.39 for 30°. Relative enhancement of the left liver lobe (LLL) was 0.58 ± 0.11 for 10° and 2.05 ± 0.61 for 30°. Relative enhancement of the RLL was significantly higher for 30° than for 10° (P = 0.009) and significantly higher in the 30° than in the 10° sequences (P = 0.005) for the LLL., Conclusion: A flip angle of 30° increases the contrast between liver partitions with and without portal venous embolization. Thereby, the sensitivity for differences in uptake intensity is increased. This could be of value for a more exact determination of differences in regional liver function and, consequently, the estimation of the future remnant liver function.

Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The majority of patients with HCC have cirrhosis. Beside liver transplantation the resection is an established curative treatment option for patients with HCC in cirrhosis. However, the long term success is limited by a high tumor recurrence rate. Furthermore, by many patients surgical resection is restricted by poor liver function. The purpose of this study was to investigate the influence of patient age on long term outcome after liver resection in patients with HCC in cirrhotic liver. Further purpose was to define the potential prognostic factors., Patients and Methods: The outcome of 141 patients with liver cirrhosis after curative resection was analyzed using a prospective database. Only patients with postoperative histological assurance of HCC were included in the database. Patients with fibrolamellar HCC were excluded., Results: By patients below 70 years of age the 1-, 3- and 5-year survival rates were 78.5%, 56.5% and 47.1%. By patients over 70 years the 1-, 3- and 5-year survival rates were 59.9%, 40.3% and 6.7%. Cumulative survival of the total collective was significant influenced by patient age, Clavien grade, positive lymph vessels, mechanical ventilation and BMI. The overall postoperative morbidity was 44.7%. No intraoperative deaths were observed, but 11 patients (8 older than 70 and 3 younger than 70 years) died during the hospital stay. Clavien grade correlated with preoperative increased GGT, need for intraoperative blood and fresh frozen plasma transfusion., Conclusions: Patient age and postoperative complications are more relevant for the outcome than many tumor factors, especially by patients over 70 years of age. In contrast, the prognosis of patients below 70 years of age is significantly better and a 5 year survival rate above 50% could be shown in our patients. However, by carefully selected elderly patients with HCC in cirrhosis an acceptable long term survival is reachable., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background and Aim: Long-term data after liver resection for hepatocellular carcinoma (HCC) with vascular invasion are rare for non-Asian patients. The aim of the present study was to analyze the long-term outcome of liver resection for HCC with vascular invasion and to compare the results of subgroups with micro- and macrovascular invasion., Methods: From January 2000 to September 2010, 288 patients without extrahepatic metastases underwent liver resection for HCC. In 107 out of 288 patients (37%), vascular invasion was found in the final pathological analysis. The long-term outcome as well as the perioperative course of these patients was analyzed using a prospective database., Results: The 1-, 3- and 5-year cumulative survival rate of HCC patients with vascular invasion was 64.3, 41.4 and 23.9%, respectively. The median survival was 19 months. In the multivariate analysis, the overall survival was not influenced by the type of vascular invasion (micro- vs. macrovascular invasion), however overall survival was significantly impaired in case of lymphatic vessel invasion, intraoperative blood transfusions, need of fresh frozen plasma application, prolonged ICU stay and elevated preoperative bilirubin levels., Conclusions: Acceptable survival rates can be achieved in selected patients with macrovascular invasion after surgical resection, which is not markedly different from those with microvascular invasion. In view of an otherwise poor prognosis, liver resection seems to be justified for selected HCC patients with macrovascular invasion, although this stands in contrast with the BCLC recommendations. However, it is in accordance for example with the guidelines of the Asia-Pacific Association for the Study of the Liver.

Complete tumor resection is still the only potentially curative therapy option for patients with ductal adenocarcinoma of the pancreas. Surgical exploration is the gold standard for the determination of tumor resectability. Radiological resectability assessment is of great importance because many clearly unresectable cases can be identified preoperatively and it became essential for surgical planning. The evolving surgical and radiological techniques demand a continuous reappraisal of radiological criteria in resectability assessment. In the following, the criteria for resection planning are described along with surgical management and the role of radiology in some innovative surgical concepts is explained., (© Georg Thieme Verlag KG Stuttgart · New York.)

Neuroendocrine tumors (NETs; syn. carcinoid tumors) are highly or moderately differentiated neoplasms. They comprise a large variety of rare and heterogeneous tumors with an estimated incidence of 3-5/100,000/year. They can arise in virtually every internal organ, but mainly occur in the gastroenteropancreatic and bronchopulmonary systems. Around 25% of the NETs are localized in the bronchopulmonary system. Approximately 2% of all lung tumors are NETs. According to the World Health Organization (WHO) classification of lung tumors, bronchopulmonary NETs are subdivided into typical carcinoids (TCs) and atypical carcinoids (ACs). The parameter with the highest impact on NET behavior and prognosis is the histological classification and staging according to the tumor/node/metastasis (TNM) system. The diagnosis of NETs is established by histological examination and the immunohistochemical detection of general neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. Serum markers and the use of functional imaging techniques are important additive tools to establish the diagnosis of a NET. The only curative option for lung NETs is complete surgical resection. Beyond that, the currently available interdisciplinary therapeutic options are local ablation, biotherapy (somatostatin analogues), or chemotherapy. New therapeutic options such as peptide receptor radionuclide therapy (PRRT) and molecularly targeted therapies achieve promising results and are under further evaluation. This report is a consensus summary of the interdisciplinary symposium 'Neuroendocrine Tumors of the Lung and of the Gastroenteropancreatic System (GEP NET) - Expert Dialogue' held on February 25-26, 2011 in Weimar, Germany. At this conference, a panel of 23 German experts shared their knowledge and exchanged their thoughts about research, diagnosis, and clinical management of NETs, whereby special attention was paid to NETs of the respiratory tract.