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Background and aims Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension. Impact of administration of aspirin on transplant-free survival after TIPS remains unknown. Methods A multicenter retrospective analysis including patients with TIPS implantation between 2011 and 2018 at three tertiary German Liver Centers was performed. N = 583 patients were included. Survival analysis was performed in a matched cohort after propensity score matching. Patients were grouped according to whether aspirin was (PSM-aspirin-cohort) or was not (PSM-no-aspirin-cohort) administered after TIPS. Primary endpoint of the study was transplant-free survival at 12 months after TIPS. Results Aspirin improved transplant-free survival 12 months after TIPS with 90.7% transplant-free survival compared to 80.0% (p = 0.001) after PSM. Separated by TIPS indication, aspirin did improve transplant-free survival in patients with refractory ascites significantly (89.6% vs. 70.6% transplant-free survival, p p = 0.797). Conclusion This retrospective multicenter study provides first data indicating a beneficial effect of aspirin on transplant-free survival after TIPS implantation in patients with refractory ascites.

In the management of patients with decompensated liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) insertion is well-established but common recommendations in the follow up management are inconsistent. Doppler sonography is commonly used for detection for TIPS dysfunction whilst data on the impact of elective invasive examinations are scarce. The aim of this retrospective analysis is to evaluate potential benefits of elective invasive examinations in the follow up management of patients after TIPS insertion METHODS: Data of all patients receiving TIPS at the university hospitals of Muenster and Bonn between 2013 and 2018 (n = 534) were collected. The impact of performance of elective invasive examinations at 12 months after TIPS insertion on the occurrence of liver related events (LREs) and frequency of TIPS revisions within 24 months after TIPS insertion was analyzed. No significant differences were found concerning occurrence of liver related events after 24 months depending on whether an elective invasive examination was performed. Occurrence of hepatic encephalopathy, relapse of initial indication for TIPS, as well as death or liver transplantation all did not differ. These findings were verified by a subgroup analysis including only patients who did not experience a LRE or TIPS revision within the first 12 months after TIPS procedure. The analyzed data suggest no evidence for a beneficial impact due to implementation of an elective invasive examination program after TIPS insertion. Invasive examinations should remain reserved to patients with suspected TIPS dysfunction. Die Anlage eines transjugulären intrahepatischen portosystemischen Shunts ist ein etabliertes Verfahren in Patienten mit dekompensierter Leberzirrhose, es fehlen jedoch einheitlich Empfehlungen in der Patientennachsorge. Die Doppler-Sonografie wird regelhaft zur Kontrolle des Shunts genutzt. Aktuell gibt es keine Daten in Bezug auf elektive invasive Kontrollen. ZIEL: Ziel dieser retrospektiven Arbeit ist die Evaluation des Einflusses elektiver invasiver TIPS-Kontrollen in der Patientennachsorge. Es wurden Daten aller Patienten, die eine TIPS Implantation an den Universitätskliniken Münster und Bonn zwischen 2013 und 2018 erhalten haben, erhoben. Der Einfluss elektiver invasiver Kontrollen zwölf Monate nach TIPS Implantation bezüglich des Auftretens leber-assoziierter Ereignisse sowie der Häufigkeit von Shunt-Revisionen wurde analysiert. Es zeigten sich keine signifikanten Unterschiede bezüglich Leber-assoziierter Ereignisse nach 24 Monaten. Unterschiede bezüglich der Häufigkeit von Episoden hepatischer Enzephalopathien, einer Rekurrenz der initialen TIPS-Indikation, sowie Todesfällen oder Lebertransplantationen konnten nicht nachgewiesen werden. In einer Subgruppen-Analyse wurden nur Patienten, die innerhalb der ersten zwölf Monate kein leber-assoziiertes Ereignis oder eine TIPS-Revision hatten, analysiert: Auch hier wurden keine Unterschiede festgestellt. Unsere Daten zeigen keinen Vorteil für Patienten durch die Implementierung elektiver invasiver Kontrollen. Invasive Kontrollen sollten Patienten mit Hinweisen auf eine Shunt-Dysfunktion vorbehalten werden.

To analyze safety and effectiveness of simultaneous portal and hepatic vein embolization (PHVE) or sequential hepatic vein embolization (HVE) compared to portal vein embolization (PVE) for future remnant liver (FRL) hypertrophy prior to major hepatic surgery. Patients undergoing PVE, PHVE or HVE at our tertiary care center between 2018 and 2020 were retrospectively included. FRLV, standardized FRLV (sFRLV) and sFRLV growth rate per day were assessed via volumetry, as well as laboratory parameters. 36 patients (f = 15, m = 21; median 64.5 y) were included, 16 patients received PHVE and 20 patients PVE, of which 4 received sequential HVE. Significant increase of FRLV was achieved with both PVE and PHVE compared to baseline (p 0.0001). sFRLV growth rate did not significantly differ following PHVE (2.2 ± 1.2 %/d) or PVE (2.2 ± 1.7 %/d, p = 0.94). Left portal vein thrombosis (LPVT) was observed after PHVE in 6 patients and in 1 patient after PVE. Sequential HVE showed a considerably high growth rate of 1.42 ± 0.45 %/d after PVE. PHVE effectively induces FRL hypertrophy but yields comparable sFRLV to PVE. Sequential HVE further induces hypertrophy after insufficient growth due to PVE. Considering a potentially higher rate of LPVT after PHVE, PVE might be preferred in patients with moderate baseline sFRLV, with optional sequential HVE in non-sufficient responders.ZIEL: Analyse von Sicherheit und Effektivität der future remnant liver (FRL) Hypertrophieinduktion vor Leberresektion durch eine simultane Pfortader- und Lebervenenembolisation (PHVE) oder sequentiellen Lebervenenembolisation (HVE) im Vergleich zur Pfortaderembolisation (PVE). Alle Patienten mit PVE, PHVE oder HVE zwischen 2018 und 2020 aus einem Universitätsklinikum wurden retrospektiv eingeschlossen. FRLV, standardisiertes FRLV (sFRLV) und sFRLV Wachstumsrate pro Tag sowie die Laborwerte wurden analysiert. 36 Patienten (f = 15, m = 21; Median: 64,5 Jahre) wurden eingeschlossen; 16 Patienten erhielten eine PHVE und 20 Patienten eine PVE (4 davon sequentielle HVE). Eine signifikante FRLV-Zunahme wurde mit der PVE und der PHVE erzielt (p 0,0001). Die sFRLV Wachstumsrate zeigte keinen signifikanten Unterschied zwischen PHVE (2,2 ± 1,2 %/d) und PVE (2,2 ± 1,7 %/d, p = 0,94). 6 bzw.1 Patient zeigten eine linksseitige Thrombose nach PHVE bzw. PVE. Die sequentielle HVE zeigte eine deutliche sFRLV Wachstumsrate von 1,42 ± 0,45 %/d. Die PHVE führt effektiv zu einer Hypertrophie, die Wachstumsrate ist jedoch vergleichbar zur PVE. Die sequentielle HVE induziert jedoch eine zusätzliche Hypertrophie nach insuffizienter PVE. Unter Berücksichtigung einer womöglich höheren Thromboserate nach PHVE, sollte die PVE bei moderatem FRL-Ausgangsvolumen bevorzugt werden, mit der Option zu einer sequentiellen HVE bei insuffizienter PVE.

SARS-CoV-2 infection can cause severe pneumonia (COVID-19). There is evidence that patients with comorbidities are at higher risk of a severe disease course. The role of immunosuppression in the disease course is not clear. In the present report, we first describe two cases of persisting SARS-CoV-2 viraemia with fatal outcome in patients after rituximab therapy.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. Methods: N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Results: Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Conclusions: Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.

Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective measure to treat complications of portal hypertension. However, liver function may deteriorate after TIPS. Predictors of liver function and outcome after TIPS are therefore important for management of TIPS patients. The study aimed to evaluate the impact of liver volume on transplant-free survival (TFS) after TIPS, as well as the evolution of liver volume and its relationship with liver function after TIPS. A retrospective analysis of all consecutive patients who underwent TIPS in a tertiary care university liver center between 2012 and 2017 (n = 216) was performed, n = 72 patients with complete prior and follow-up (FU) computed tomography (CT) imaging studies were included in the study. Volumetry of the liver was performed by a semi-automatic 9-lobe image segmentation algorithm at baseline and FU (FU 1: 90–180 d, FU 2: 180–365 d, FU 3: 365–545 d, FU 4: 545–730 d, FU 5: &gt, 730 d). Output variables were total liver volume (TLV, cm3), left liver volume (LLV, cm3), right liver volume (RLV, cm3) and TLV/body weight ratio. CT derived liver volumes were correlated with liver function tests, portosystemic pressure gradient (PPG) measurements and survival. To assess predictors of liver volume change over time we fitted linear mixed models. Kaplan–Meier analysis was performed and validated by matched pair analysis followed by Cox regression to determine independent prognostic factors for survival. The median TLV at baseline was 1507.5 cm3 (773.7–3686.0 cm3). Livers with higher baseline liver volumes and larger TLV/weight ratios retained their volume after an initial loss while smaller livers continuously lost volume after TIPS. At the first follow-up period (90–180 d post-TIPS) lower liver volumes and TLV/weight ratios were associated with higher bilirubin levels. Within the final multivariable model containing time (days since TIPS), baseline INR and baseline TLV, the average loss of liver volume was 0.74 mL per day after TIPS. Twelve-month overall transplant-free survival was 89% and median overall TFS was 33 months. The median TFS for a baseline TLV/body weight ratio &gt, 20 was significantly higher compared with ≤ 20 (40.0 vs. 27.0 months, p = 0.010) while there were no differences regarding the indication for TIPS or etiology of liver disease in the matched pair analysis. Lower TLV/weight ratios before TIPS were associated with shorter TFS and should therefore be critically considered when selecting patients for TIPS. In addition, this study provides first evidence of an effect of TIPS on subsequent liver volume change and associated liver function.

Precise segmentation of objects is an important problem in tasks like class-agnostic object proposal generation or instance segmentation. Deep learning-based systems usually generate segmentations of objects based on coarse feature maps, due to the inherent downsampling in CNNs. This leads to segmentation boundaries not adhering well to the object boundaries in the image. To tackle this problem, we introduce a new superpixel-based refinement approach on top of the state-of-the-art object proposal system AttentionMask. The refinement utilizes superpixel pooling for feature extraction and a novel superpixel classifier to determine if a high precision superpixel belongs to an object or not. Our experiments show an improvement of up to 26.0% in terms of average recall compared to original AttentionMask. Furthermore, qualitative and quantitative analyses of the segmentations reveal significant improvements in terms of boundary adherence for the proposed refinement compared to various deep learning-based state-of-the-art object proposal generation systems., Comment: Accepted at ICPR 2020. Code is available at https://github.com/chwilms/superpixelRefinement

The detection of logos in images, for instance, logos of airlines on airplane tails, is a difficult task in real-world weather conditions. Most systems used for logo detection are very good at detecting logos in clean images. However, they exhibit problems when images are degraded by effects of adverse weather conditions as they frequently occur in real-world scenarios. For investigating this problem on airline logo detection as a subproblem of logo detection, we first present a new dataset for airline logo detection on airplane tails containing a test split with images degraded by adverse weather effects. Second, to handle the detection of airline logos effectively, a new two-stage airline logo detection system based on a state-of-the-art object proposal generation system and a specifically tailored classifier is proposed. Finally, improving the results on images degraded by adverse weather effects, we introduce a learning-free application-agnostic data augmentation strategy simulating effects like rain and fog. The results show the superior performance of our airline logo detection system compared to state-of-the-art. Furthermore, applying our data augmentation approach to a variety of systems, reduces the significant drop in performance on degraded images.

Class-agnostic object proposal generation is an important first step in many object detection pipelines. However, object proposals of modern systems are rather inaccurate in terms of segmentation and only roughly adhere to object boundaries. Since typical refinement steps are usually not applicable to thousands of proposals, we propose a superpixel-based refinement system for object proposal generation systems. Utilizing precise superpixels and superpixel pooling on deep features, we refine initial coarse proposals in an end-to-end learned system. Furthermore, we propose a novel DeepFH segmentation, which enriches the classic Felzenszwalb and Huttenlocher (FH) segmentation with deep features leading to improved segmentation results and better object proposal refinements. On the COCO dataset with LVIS annotations, we show that our refinement based on DeepFH superpixels outperforms state-of-the-art methods and leads to more precise object proposals., Comment: Accepted by IVC

BackgroundCholangiocarcinoma (CCA) is a rare malignant tumor of the bile duct epithelium. At first diagnosis, only a minority of patients is eligible for surgery, which is regarded as the only curative treatment. This study examines the role of radiation therapy (RT) and chemoradiotherapy (CRT) in the definitive and adjuvant treatment situation.MethodsThe monocentric retrospective analysis included 39 patients (31 males, 8 females) with CCA undergoing 53 RT series. Data was collected from January 2005 to September 2018. There were 11 cases of CRT, 6 of which were definitive. Surgery was either palliative (n=6) or radical (n=15).ResultsAfter RT, median overall survival (OS) was 10.4 months (mo; 95% confidence interval [CI] 6.6-14.2), median progression-free survival (PFS) was 5.6 mo (95% CI 3-8.2), median duration of local control (DOLC) was 8.9 mo (95% CI 4.7-13.1) and 1-year OS rate was 44.7%. There was a significant difference between patients with and without locoregional lymph node metastasis (OS: 4.3 mo vs. 15.4 mo, p=0.031; PFS: 2.1 mo vs. 11.5 mo, pConclusionRT can achieve local control in patients with CCA. However, since overall prognosis remains poor, effective combination therapies are needed. Toxicities of RT are manageable but require close clinical and laboratory follow-up.

Purpose To analyze patients’ characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after 99mTc-labeled macroaggregated albumin (99mTc-MAA) evaluation. Methods In this retrospective single-center cohort, all patients undergoing 99mTc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either “TARE” or “no TARE” group. Patients’ characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed. Results 436 patients [male = 248, female = 188, median age 62 (23–88) years] with 99mTc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in “no TARE” compared to “TARE” group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of 99mTc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031). Conclusion A substantial number of patients are precluded from TARE following 99mTc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.

Background and Aims The organ shortage especially in blood group 0 forces transplant professionals to discuss new approaches to expand the donor pool. Recently, the successful therapy of HCV with direct antiviral agents in kidney transplanted patients has made the transplantation of HCV-infected kidneys to uninfected patients possible. Furthermore, these organs promise an above-average organ function as HCV-infected donors are usually young and have fewer comorbidities. Since there is no standard procedure for the treatment of kidney recipients with HCV grafts, we compared a preemptive and a prophylactic approach using direct antiviral drugs after kidney transplantation of two patients. Method We report the transplantation of two HCV-positive kidneys. One recipient was a 49-year-old female patient, who suffered from ESRD caused by an atypical hemolytic uremic syndrome. The other recipient had autosomal dominant polycystic kidney disease. Since the genotype of the HCV donor was unknown at the time of transplantation, we decided to use the pangenotypic, fixed-dose combinations Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir. Results Both patients had blood group 0 and received an AB0-compatible kidney transplant. The initial immunosuppressive therapy consisted of prednisolone, mycophenolate sodium, and tacrolimus. Furthermore, an induction therapy with Basiliximab was given. The first patient received Glecaprevir/Pibrentasvir immediately post-surgery. Treatment was carried on for eight weeks as a prophylactic approach. Frequent HCV-PCRs showed negative results over six months. However, the patient developed anti-HCV antibodies within six days after transplantation. The graft started working on postoperative day four, and the serum creatinine decreased to 1.33 mg/dl on the discharge day and stabilized on this level during further follow-up. Following a preemptive approach, our second patient was treated with Sofosbuvir/Velpatasvir after detection of HCV RNA and rising levels of transaminases on post-transplant day 7. This patient also received Entecavir because of a previous HBV-infection of the donor (non-viremic on the day of transplantation). The graft started working on day two, and the serum creatinine decreased to 1.28 mg/dl on the discharge day and stabilized on this level. Further HCV-PCRs also showed negative results. Conclusion We conclude that kidneys from HCV-viremic donors can be transplanted with precaution. Both therapeutic strategies showed equally good results and can easily be implemented into kidney transplantation. Especially, the combination of Glecaprevir/Pibrentasvir offers a safe HCV prophylaxis without the need of adaptions to the renal function or HCV genotype. In case of a permanent absence of a HCV infection, the preemptive approach offers a chance to avoid the HCV-therapy. On the other hand, causing an iatrogenic infection of HCV in a patient with immunosuppression brings up ethical issues due to the risk of HCV-related liver diseases. Therefore, we favor the prophylactic approach. Further studies are needed to identify the optimal time frame for direct antiviral agents in HCV (D+/R-) transplantations.

Renal impairment is a typical side effect of tacrolimus (Tac) treatment in liver transplant (LT) recipients. One strategy to avoid renal dysfunction is to increase the concentration/dose (C/D) ratio by improving drug bioavailability. LT recipients converted from standard-release Tac to MeltDose® Tac (LCPT), a novel technological formulation, were able to reduce the required Tac dose due to higher bioavailability. Hence, we hypothesize that such a conversion increases the C/D ratio, resulting in a preservation of renal function. In the intervention group, patients were switched from standard-release Tac to LCPT. Clinical data were collected for 12 months after conversion. Patients maintained on standard-release Tac were enrolled as a control group. Twelve months after conversion to LCPT, median C/D ratio had increased significantly by 50% (p < 0.001), with the first significant increase seen 3 months after conversion (p = 0.008). In contrast, C/D ratio in the control group was unchanged after 12 months (1.75 vs. 1.76; p = 0.847). Estimated glomerular filtration rate (eGFR) had already significantly deteriorated in the control group at 9 months (65.6 vs. 70.6 mL/min/1.73 m2 at study onset; p = 0.006). Notably, patients converted to LCPT already had significant recovery of mean eGFR 6 months after conversion (67.5 vs. 65.3 mL/min/1.73 m2 at study onset; p = 0.029). In summary, conversion of LT recipients to LCPT increased C/D ratio associated with renal function improvement.

Purpose: To evaluate predictive parameters for the development of Hepatic Encephalopathy (HE) after Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement and for success of shunt modification in the management of shunt-induced HE. Methods: A retrospective analysis of all patients with TIPS (n = 344) has been performed since 2011 in our university liver center. n = 45 patients with HE after TIPS were compared to n = 48 patients without HE after TIPS (case-control-matching). Of n = 45 patients with TIPS-induced HE, n = 20 patients received a reduction stent (n = 18) or TIPS occlusion (n = 2) and were differentiated into responders (improvement by at least one HE grade according to the West Haven classification) and non-responders (no improvement). Results: Older patient age, increased serum creatinine and elevated International Normalized Ratio (INR) immediately after TIPS placement were independent predictors for the development of HE. In 11/20 patients (responders, 55%) undergoing shunt modification, the HE grade was improved compared with nine non-responders (45%), with no relevant recurrence of refractory ascites or variceal bleeding. A high HE grade after TIPS insertion was the only positive predictor of treatment response (p = 0.019). A total of 10/11 responders (91%) survived the 6 months follow-up after modification but only 6/9 non-responders (67%) survived. Discussion: Older patient age as well as an increased serum creatinine and INR after TIPS are potential predictors for the development of HE. TIPS reduction for the treatment of TIPS-induced HE is safe, with particular benefit for patients with pronounced HE.

Background With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT. Material and methods A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death. Results The mean age of recipients at the time of LT was 50.3 ± 12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ± 15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p Conclusion Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.

Supplemental Digital Content is available in the text., Objectives: Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial. Design: Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria. Setting: Medical Departments of University Hospital Muenster (Germany). Patients: This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1–3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial. Interventions: Standard medical treatment and molecular adsorbent recirculating system. Measurements and Main Results: Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2–3). Concerning the affected organ system, this effect of molecular adsorbent recirculating system on mortality was particularly evident among patients with increased kidney, brain, or coagulation Chronic Liver Failure-C-Organ Failure subscores. Subsequent reanalysis of the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure dataset with adoption of the Chronic Liver Failure-classification resulted in similar findings. Conclusions: Molecular adsorbent recirculating system treatment was associated with an improved short-term survival of patients with acute-on-chronic liver failure and multiple organ failure. Among these high-risk patients, molecular adsorbent recirculating system treatment might bridge to liver recovery or liver transplantation.

Background Portal hypertension is a major complication of liver cirrhosis. Transjugular intrahepatic portosystemic shunt is effective in treatment of portal hypertension. However, decreased parenchymal portal venous flow after transjugular intrahepatic portosystemic shunt insertion favours ischaemic liver injury which has been discussed to induce hepatocarcinogenesis causing hepatocellular cancer. Aim This study aimed to explore the association between transjugular intrahepatic portosystemic shunt placement and the development of hepatocellular cancer. Methods A total of 1338 consecutive liver cirrhosis patients were included in this retrospective study between January 2004–December 2015. Data were analysed with regard to development of hepatocellular cancer during follow-up. Binary logistic regression and Kaplan-Meier analyses were conducted for the assessment of risk factors for hepatocellular cancer development. In a second step, to rule out confounders of group heterogeneity, case-control matching was performed based on gender, age, model of end-stage liver disease score and underlying cause of cirrhosis (non-alcoholic steatohepatitis, alcoholic liver disease and viral hepatitis). Results Besides established risk factors such as older age, male gender and underlying viral hepatitis, statistical analysis revealed the absence of transjugular intrahepatic portosystemic shunt insertion as a risk factor for hepatocellular cancer development. Furthermore, matched-pair analysis of 432 patients showed a significant difference ( p = 0.003) in the emergence of hepatocellular cancer regarding transjugular intrahepatic portosystemic shunt placement versus the non-transjugular intrahepatic portosystemic shunt cohort. Conclusion In patients with end-stage liver disease, transjugular intrahepatic portosystemic shunt insertion is significantly associated with reduced rates of hepatocellular cancer development.

Objective To evaluate the effectiveness of interventional therapy in acute, non-malignant, non-cirrhotic portal vein thrombosis. Methods We present a retrospective study of eight consecutive patients who presented with an acute non-malignant, non-cirrhotic portal vein thrombosis and were treated by mechanical recanalization using an escalating scheme including local aspiration, thrombolysis, rheolysis and the implantation of transjugular intrahepatic portosystemic shunt or other visceral stents. Results Recanalization rates applying the escalating scheme were good, with a success rate of 75%. However, major complications occurred in 50% of patients, mostly due to bleeding at the percutaneous access site, and minor complications in 12.5% of patients. Conclusion Interventional therapy is effective in acute portal vein thrombosis, but should only be performed at specialized centers and based on an individual treatment decision.

We propose a novel approach for class-agnostic object proposal generation, which is efficient and especially well-suited to detect small objects. Efficiency is achieved by scale-specific objectness attention maps which focus the processing on promising parts of the image and reduce the amount of sampled windows strongly. This leads to a system, which is \(33\%\) faster than the state-of-the-art and clearly outperforming state-of-the-art in terms of average recall. Secondly, we add a module for detecting small objects, which are often missed by recent models. We show that this module improves the average recall for small objects by about \(53\%\). Our implementation is available at: https://www.inf.uni-hamburg.de/en/inst/ab/cv/people/wilms/attentionmask.

Background: The aim of this study was to compare arterial embolization (AE) with portal vein embolization (PVE) for the induction of segmental hypertrophy regarding procedural efficacy, safety and outcome. Methods: A total of 29 mini pigs were subjected to PVE, AE or assigned to the sham (SO) group. Correspondingly, 75% of the hepatic artery or portal vein branches were embolized. Growth and atrophy of the liver lobes, calculating the liver-to-body weight index (LBWI), laboratory data, arteriography, portography, Doppler ultrasound (US) and histopathology were analyzed. Results: After PVE, 2 animals had to be excluded due to technical problems. After AE, 4 animals had to be excluded because of technical problems and early sacrifice. Postprocedural US demonstrated effective AE and PVE of the respective lobes. Four weeks after PVE, portography showed a slow refilling of the embolized lobe by collateral portal venous vessels. Four weeks after AE, arteriography revealed a slight revascularization of the embolized lobes by arterial neovascularization. Segmental AE led to extensive necrotic and inflammatory alterations in the liver and bile duct parenchyma. Significant hypertrophy of the non-embolized lobe was only noted in the PVE group (LBWI: 0.91 ± 0.28%; p = 0.001). There was no increase in the non-embolized lobe in the AE (LBWI: 0.45 ± 0.087%) and SO group (LBWI: 0.45 ± 0.13%). Conclusion: PVE is safe and effective to induce segmental hypertrophy. Portal reperfusion by collateral vessels may limit hypertrophy. AE did not increase the segmental hepatic volume but carries the risk of extensive necrotic inflammatory damage.

Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction. Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts. Results: MTD was 3 mg/m2 tTF-NGR/day &times, 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t1/2(terminal) of 8 to 9 h without accumulation in daily administrations. Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.

Background. Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. Methods. All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. Results. A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). Conclusion. Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied.

Background Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. Methods In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. Results Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 × 10−6) and microvascular invasion (P = 1.31 × 10−5) were significantly associated with survival in a Cox regression analysis. Conclusions Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered., The authors of this multicenter retrospective study assess whether the evolutionary distance measured from genome-wide single nucleotide polymorphism (SNP) data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after liver transplantation for multifocal hepatocellular carcinoma. Supplemental digital content is available in the text.

With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT.A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death.The mean age of recipients at the time of LT was 50.3 ± 12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ± 15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p 0.001), pretransplant diabetes mellitus (p = 0.03), and/or marked fibrosis in the initial protocol biopsy during follow-up (p = 0.001) to be recipient-related significant and independent risk factors for allograft failure following LT.Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.Im Hinblick auf die Lebensqualität und den herrschenden Organmangel sollte die Nachsorge nach einer Lebertransplantation (LT) Risikofaktoren für eine Transplantatdysfunktion berücksichtigen, um sowohl die Langzeitergebnisse zu verbessern als auch Retransplantationen zu vermeiden. Ziel dieser Studie war es daher Risikofaktoren für ein Organversagen nach einer LT zu evaluieren.489 lebertransplantierte Patienten wurden konsekutiv in diese retrospektive Studie eingeschlossen. Es wurde eine Datenbankrecherche durchgeführt. Mittels einer binären Regressionsanalyse wurden potentielle Risikofaktoren eines Transplantatversagens nach einer LT ermittelt. Als Transplantatversagen wurden eine Transplantatzirrhose, die Notwendigkeit einer Re-LT und der transplantatassoziierte Tod definiert.Das mittlere LT-Empfängeralter lag bei 50,3 ± 12,4 Jahren. 64 % der Empfänger waren männlich. Das Spenderalter lag bei 48,7 ± 15,5 Jahren. Die statistische Analyse ergab folgende unabhängige Risikofaktoren für ein Transplantatversagen: männliches Empfängergeschlecht (p = 0,04), Hepatitis-C-Virus-Infektion (HCV) (p = 0,014) und hepatozelluläres Karzinom (HCC) (p = 0,03) als Grunderkrankung, Prätransplantationsdiabetes (p = 0,03) sowie biliäre Komplikationen (p 0,001) und/oder deutliche Fibrose in der Protokoll-Biopsie während der Nachsorgezeit (p = 0,001).Männliche Empfänger, Patienten mit HCV bzw. HCC als Grunderkrankungen, solche mit Prätransplantationsdiabetes sowie LT-Empfänger mit biliären Komplikationen haben ein erhöhtes Risiko für ein Transplantatversagen und sollten daher speziell hinsichtlich dieser Risikofaktoren nachgesorgt werden.

Perihilar cholangiocarcinomas are often considered incurable. Late diagnosis is common. Advanced disease therefore frequently causes questioning of curative surgical outcome.This study aimed to develop a prediction model of curative surgery in patients suffering from perihilar cholangiocarcinomas based on preoperative endosonography and computer tomography.A cohort of 81 patients (median age 67 (54-75) years, 62% male) with perihilar cholangiocarcinoma was retrospectively analyzed. Multivariate logistic regression analysis of staging variables taken from the European Staging System was performed and applied to ROC analysis.The correlation of predicted rates of eligibility for surgery with actual rates reached AUC values between 0.652 and 0.758 for endosonography and computer tomography (Our predictive web-based model pSurg with inclusion of T, N, M, B, PV, HA and V stage of the recently published European Staging System for perihilar cholangiocarcinoma results in highly significant predictability for curative surgery when combining preoperative endosonography and computer tomography, thus allowing for better patient selection in terms of possibility of curative surgery.

Background The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. Aim We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). Methods We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). Results The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3–5 sessions). Independent of the underlying etiology, MARS improved the patients’ bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0–15.3); SMT 3.3% (95% CI: 0–9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0–44.7), SMT 11.1% (95% CI: 0–31.7), p = 0.478). Conclusions Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease.

Due to advances in immunosuppressive therapy and surgical techniques, survival rates after solid organ transplantation have constantly improved over the last decades. In long-term care after transplantation, physicians need to focus as much on diagnosis and treatment of allograft-related complications as they should consider comorbidities and evaluate risk-factors and adverse events of immunosuppressive agents to prevent secondary diseases. In particular, cardiovascular and metabolic diseases, malignancy and infection play a major role in long-term survival. Therefore, screening of organ transplant recipients in regard to these complications and adverse events is a crucial part of follow up in these patients.

Carbon fiber is expected to increase its importance as a lightweight substitute material. The significant market potential in the automotive industry is strongly dependent on carbon fiber cost. A decrease of about 50% from the present cost level of polyacrylonitrile (PAN)-based carbon fibers is needed. This ambitious target is only achievable with high-cost transparency in the production chain. This paper reviews published cost models and identifies the need for a consistent methodology and transparency over input parameters. A new cost model with a modular structure covering all process steps by cost type and disclosing all process parameter assumptions is introduced. The most cost-intense steps are polymerization, including raw material (25%), carbonization (22%) and fiber washing after coagulation (19%). Most important cost types are energy (34%), raw material (19%) and capital costs for equipment (18%). The high-cost share of 54% for carbon fiber PAN precursor is consistent with most reviewed models.

The ethical and legal challenges of biomedical research are among the most crucial and interesting questions in law nowadays. One of these questions concerns the regulation of research on human genetic data in transnational constellations. Genetic research promises therapies and prevention for diseases like cancer and HIV, but it is highly dependent on genetic material derived from donors of tissue or blood. For significant advancements in cancer research, for instance, a large number of genetic data of patients is needed. Such data are most effectively collected in and made available by databases or biobanks that allow the exchange of genetic data by various research facilities. To enhance the possibilities and enlarge the amount of genetic data available for researchers the European Union through its 6th Framework Programme of the European Commission under the Action Line �Integrated biomedical information for better health� funded the so-called �Advancing Clinico-Genomic Trials on Cancer� research project (ACGT). This project aimed to deliver to the cancer research community an integrated clinico-genomic information and communication technology environment designed to become a pan-European voluntary network connecting individuals and institutions to enable the sharing of data and tools. However, broadening the scope to the European level causes problems of integration of different national views on ethical issues and their legal framework. The book under review presents some of the findings of the ethical and legal section of the project. The authors, specialists in the field of data protection, data security, and technology assessment, scrutinized the necessary framework for a pan-European infrastructure for medical researchers aiming at a bigger pool of genetic material for research on various types of cancer. Recognizing the necessary link between law and ethics in the realm of biomedical research, the authors combined both of these aspects to provide a holistic socio-scientific analysis of the project, �

Die gesteigerte Nutzung von Leichtbaupotenzialen und die Eigenschaften von Carbonfasern werden zu einer erhohten Nachfrage nach diesem Werkstoff fuhren. Fachleute sehen darin einen sehr attraktiven Markt fur viele Unternehmen der Chemieindustrie. Gleichzeitig ist der Carbonfasermarkt eine vergleichsweise junge Branche, in der viele Verschiebungen und Neukonstellationen zu beobachten sind. Dieser Beitrag gibt einen Marktuberblick.