Publications by authors named "Christian Wilms"

47 Publications

Short- and Long-Term Outcomes of Different Reperfusion Sequences in Liver Transplantation.

Ann Transplant 2021 Feb 19;26:e926847. Epub 2021 Feb 19.

Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany.

BACKGROUND Although most centers perform primary portal vein reperfusion (PV) in orthotopic liver transplantation (OLT) for historical reasons, there is so far no sound evidence as to whether this technique is superior. The present study evaluated the long-term outcome of 3 different reperfusion sequences: PV vs primary arterial (A) vs simultaneous reperfusion (SIM). MATERIAL AND METHODS All patients at our center who underwent OLT (who received a primary, whole-organ liver graft) from 2006 to 2007 were evaluated for analysis. RESULTS A total of 61 patients were found eligible (PV: 25, A: 22, SIM: 14). Twenty-one patients (35%) were still alive after the follow-up period of 12 years. Despite poorer starting conditions such as higher recipient age (59 y (SIM) vs 55 y (A) vs 50 y (PV), P=0.01) and donor age (56 y (SIM) vs 51 y (PV) vs 50 y (A), n.s.), higher MELD scores (22 vs 19 (PV) vs 17 (A), n.s.), as well as a higher number of marginal donor organs (79% (SIM) vs 36% (A/PV), P=0.02), SIM-recipients demonstrated superior outcomes. Overall survival was 8.1 y (SIM), 4.8 y (PV), and 5.9 y (A, n.s.)). None of the SIM-recipients underwent re-transplantation, while the rate was 32% in the PV-group. The 8.1 y graft survival in SIM-recipients was significantly longer than in the other 2 groups, which were 3.3 y (PV) and 5.5 y (A, P=0.013). CONCLUSIONS Although SIM-reperfused recipients were the oldest and received grafts of inferior quality, these recipients showed superior results in terms of overall patient and graft survival. Multicentric randomized controlled trials with larger study populations are required to confirm this finding.
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http://dx.doi.org/10.12659/AOT.926847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901155PMC
February 2021

Portal and hepatic vein embolization prior to major hepatectomy.

Z Gastroenterol 2021 Jan 11;59(1):35-42. Epub 2021 Jan 11.

Department for General, Visceral and Transplantation Surgery, University Hospital Muenster, Muenster, Germany.

Purpose:  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.

Methods:  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.

Results:  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.

Conclusion:  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.
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http://dx.doi.org/10.1055/a-1330-9450DOI Listing
January 2021

Evaluation of impact of elective invasive examinations in patients with transjugular intrahepatic portosystemic shunt in the long-term follow up.

Z Gastroenterol 2021 Jan 11;59(1):24-34. Epub 2021 Jan 11.

Medical Clinic B, Department of Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology, University Hospital Muenster, Muenster, Germany.

Introduction:  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.

Aim:  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.

Results:  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.

Conclusion:  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.
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http://dx.doi.org/10.1055/a-1330-9867DOI Listing
January 2021

Analysis of failed therapy evaluations in radioembolization of primary and secondary liver cancers.

J Cancer Res Clin Oncol 2020 Nov 6. Epub 2020 Nov 6.

Institute of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Munster, Germany.

Purpose: To analyze patients' characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after Tc-labeled macroaggregated albumin (Tc-MAA) evaluation.

Methods: In this retrospective single-center cohort, all patients undergoing Tc-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 Tc-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 Tc-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 Tc-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.
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http://dx.doi.org/10.1007/s00432-020-03443-zDOI Listing
November 2020

Repeated radioembolization in advanced liver cancer.

Ann Transl Med 2020 Sep;8(17):1055

Institute of Clinical Radiology, University Hospital Muenster, Muenster, Germany.

Background: To evaluate safety and clinical outcome of repeated transarterial Y (yttrium) radioembolization (TARE) in primary and metastatic liver cancer.

Methods: Between 2009 and 2018, n=288 patients underwent TARE for treatment of malignant liver disease in a tertiary care hospital. This retrospective single center study analyzed the safety and outcome of patients (n=11/288) undergoing repeated resin microsphere TARE. Included patients suffered from hepatocellular carcinoma (n=3), colorectal cancer (n=2), breast cancer (n=2), intrahepatic cholangiocarcinoma (n=3), and neuroendocrine carcinoma (n=1). All patients had shown either partial response (n=9) or stable disease (n=2) after first TARE. Lab parameters, response assessed by the Response Evaluation Criteria in Solid Tumors (mRECIST/RECIST) at 3 months and overall survival was analyzed. Additionally, patients with repeated TARE were compared to a matched control group (n=56) with single TARE therapy. Kaplan Meier analysis was performed to analyze survival.

Results: Patients after repeated TARE showed similar increase in lab parameters as compared to their first TARE. No case of radioembolization induced liver disease was observed. While n=5/11 patients showed a partial response and n=4/11 patients a stable disease after repeated TARE, only n=2/11 patients suffered from progressive disease. Median overall survival was 20.9±11.9 months for the repeated TARE group while it was 5.9±16.2 months for the control group.

Conclusions: Repeated Y TARE is safe and can be of benefit for patients yielding a comparable degree of local disease control compared to patients with singular TARE.
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http://dx.doi.org/10.21037/atm-20-2658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575953PMC
September 2020

Persisting SARS-CoV-2 viraemia after rituximab therapy: two cases with fatal outcome and a review of the literature.

Br J Haematol 2020 07 22;190(2):185-188. Epub 2020 Jun 22.

Department of Gastroenterology and Hepatology, Section for Infectious Diseases, University Hospital Muenster, Muenster, Germany.

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.
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http://dx.doi.org/10.1111/bjh.16896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300950PMC
July 2020

First-In-Class CD13-Targeted Tissue Factor tTF-NGR in Patients with Recurrent or Refractory Malignant Tumors: Results of a Phase I Dose-Escalation Study.

Cancers (Basel) 2020 Jun 7;12(6). Epub 2020 Jun 7.

Department of Medicine A, Hematology, Oncology, University Hospital Muenster, D-48149 Muenster, Germany.

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/m tTF-NGR/day × 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 t 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.
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http://dx.doi.org/10.3390/cancers12061488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352358PMC
June 2020

Conversion from Standard-Release Tacrolimus to MeltDose Tacrolimus (LCPT) Improves Renal Function after Liver Transplantation.

J Clin Med 2020 Jun 1;9(6). Epub 2020 Jun 1.

Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, 48149 Münster, Germany.

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% ( < 0.001), with the first significant increase seen 3 months after conversion ( = 0.008). In contrast, C/D ratio in the control group was unchanged after 12 months (1.75 vs. 1.76; = 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 m at study onset; = 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 m at study onset; = 0.029). In summary, conversion of LT recipients to LCPT increased C/D ratio associated with renal function improvement.
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http://dx.doi.org/10.3390/jcm9061654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356524PMC
June 2020

TIPS Modification in the Management of Shunt-Induced Hepatic Encephalopathy: Analysis of Predictive Factors and Outcome with Shunt Modification.

J Clin Med 2020 Feb 19;9(2). Epub 2020 Feb 19.

Institute of Clinical Radiology, University Hospital Muenster, D-48149 Muenster, Germany.

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 ( = 344) has been performed since 2011 in our university liver center. = 45 patients with HE after TIPS were compared to = 48 patients without HE after TIPS (case-control-matching). Of = 45 patients with TIPS-induced HE, = 20 patients received a reduction stent ( = 18) or TIPS occlusion ( = 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 ( = 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.
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http://dx.doi.org/10.3390/jcm9020567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073830PMC
February 2020

Escalating interventional recanalization therapy in non-cirrhotic, non-malignant acute portal vein thrombosis.

Eur J Gastroenterol Hepatol 2019 Dec;31(12):1584-1591

Institute of Clinical Radiology, University Hospital Münster, Münster, Germany.

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.
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http://dx.doi.org/10.1097/MEG.0000000000001559DOI Listing
December 2019

Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation.

Can J Gastroenterol Hepatol 2019 8;2019:5796074. Epub 2019 Jan 8.

Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, 48149 Muenster, Germany.

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 (; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (; 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.
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http://dx.doi.org/10.1155/2019/5796074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341263PMC
June 2019

The role of immediate versus secondary removal of the odontogenic focus in treatment of deep head and neck space infections. A retrospective analysis of 248 patients.

Clin Oral Investig 2019 Jul 8;23(7):2921-2927. Epub 2019 Jan 8.

Department of Oral & Maxillofacial Plastic Surgery, University hospital Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.

Objectives: Aim of this study was to investigate conditions and predisposing factors for head and neck infection progress regarding the length of stay (LOS) in hospital, with special emphasis on the time of removal of the odontogenic infection focus.

Material And Methods: A 3-year retrospective study reviewed hospital records of 248 subjects who were treated under inpatient conditions with severe odontogenic infections who received surgical incisions, drainage, and intravenous (IV) antibiotics. Outcomes measured included age, gender, involved fascial spaces, LOS, number of infected spaces, antibiotics administered, and comorbidities. We precisely recorded the time between abscess incision and focus extraction.

Results: Removal of infection focus (tooth) in the same stay (1 stay, n = 106; group 1; mean 6.5 days ± 3) showed significantly higher (p = 0.042) LOS than extraction in a second stay (2 stays, n = 46; group 2; 5.3 ± 3.1). Group 3 patients showed infection after removal of teeth in outpatient management (1 stay ex-op, n = 96) and presented significantly lower LOS (5.6 ± 2.5) compared to group 1 (p = 0.0216). LOS of group 3 to group 2 patients showed no significance (p = 0.668). Infection expansion and diabetes showed a significant increase of LOS.

Conclusion: Simultaneous removal of infection focus and abscess incision leads to the lowest LOS. If tooth extraction is performed after incision, subsequent focus extraction performed in a second stay shows lower overall-LOS than extraction at the same stay at later stage.

Clinical Relevance: Multiple factors tend to increase the LOS of patients with severe head and neck infections of odontogenic origin. Our data reveals the role of removal of odontogenic focus and additionally ranks further parameters that influence the LOS. Based on our findings, decisions regarding the surgical treatment can be recommended.
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http://dx.doi.org/10.1007/s00784-018-02796-7DOI Listing
July 2019

Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma.

Transplantation 2018 10;102(10):e424-e430

Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Germany.

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) and microvascular invasion (P = 1.31 × 10) 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.
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http://dx.doi.org/10.1097/TP.0000000000002356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598094PMC
October 2018

Preoperative prediction of curative surgery of perihilar cholangiocarcinoma by combination of endoscopic ultrasound and computed tomography.

United European Gastroenterol J 2018 Mar 25;6(2):263-271. Epub 2017 May 25.

Department of Transplant Medicine, University of Münster, Münster, Germany.

Background: Perihilar cholangiocarcinomas are often considered incurable. Late diagnosis is common. Advanced disease therefore frequently causes questioning of curative surgical outcome.

Aim: This study aimed to develop a prediction model of curative surgery in patients suffering from perihilar cholangiocarcinomas based on preoperative endosonography and computer tomography.

Methods: 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.

Results: 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 ( < 0.05 each). Best prediction for curative surgical option was achieved by combining endosonography and computer tomography (AUC: 0.787; 95% CI 0.680-0.893,  < 0.0001). A predictive model (pSurg) was developed using multivariate analysis.

Conclusions: 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.
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http://dx.doi.org/10.1177/2050640617713651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833220PMC
March 2018

Risk factors for allograft failure in liver transplant recipients.

Z Gastroenterol 2018 07 16;56(7):745-751. Epub 2018 Jan 16.

University Hospital Muenster, Department of Medicine B, Gastroenterology and Hepatology, Muenster, Germany.

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 < 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.

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.
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http://dx.doi.org/10.1055/s-0043-125225DOI Listing
July 2018

Vitamin D (25-OHD) deficiency may increase the prevalence of medication-related osteonecrosis of the jaw.

J Craniomaxillofac Surg 2017 Dec 23;45(12):2068-2074. Epub 2017 Sep 23.

Department for Oral & Cranio-Maxillo and Facial Plastic Surgery (Head: Prof. Dr. Dr. Rudolf H. Reich), University of Bonn, Bonn, Germany. Electronic address:

Introduction: Osteonecrosis of the jaw (ONJ) is a severe complication of antiresorptive medication (AM) in the treatment of bone-affecting cancer-related conditions and osteoporosis. Aim of this study was to reveal whether patients treated with AM and show Medication Related OsteoNecrosis of the Jaw (MRONJ) are vitamin D deficient or not.

Materials And Methods: A 2 year retrospective study evaluated hospital records of 63 patients who received AM. Patients were divided into two groups. One group (n = 45) consisted of patients who presented a stage 2 ONJ (eb+ = exposed bone). Second group patients (n = 18) (eb- = no exposed bone) presented for extraction of teeth. Serum levels of vitamin D (25-OHD) were analysed. P values ≤ 0.05 in t-test were regarded as statistically significant.

Results: Serum levels of 25-OHD were significantly higher in the eb(-) group (29.5 ng/ml), than in the eb(+) group (20.49 ng/ml). Blood levels of calcium were also significantly higher in eb(-) group (2.25 mmol/L; 0.11 SD) than in eb(+) group (2.175 mmol/L; 0.16 SD).

Conclusion: Prevalence of MRONJ in AM treated patients seems to be increased by low serum 25-OHD. A measurable tendency in the role of 25-OHD for the development of MRONJ was recorded and leads to the recommendation for a sufficient vitamin D substitution in patients treated with AM.
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http://dx.doi.org/10.1016/j.jcms.2017.09.015DOI Listing
December 2017

Single-operator cholangioscopy for biliary complications in liver transplant recipients.

World J Gastroenterol 2017 Jun;23(22):4064-4071

Anna Hüsing-Kabar, Hauke Sebastian Heinzow, Hartmut Hans-Jürgen Schmidt, Carina Stenger, Christian Wilms, Iyad Kabar, Department of Transplant Medicine, University Hospital Muenster, 48149 Muenster, Germany.

Aim: To evaluate cholangioscopy in addition to endoscopic retrograde cholangiopancreatography (ERCP) for management of biliary complications after liver transplantation (LT).

Methods: Twenty-six LT recipients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between April and December 2016 at the university hospital of Muenster were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis and bile was collected during the intervention for microbial analysis and for antibiotic susceptibility testing.

Results: Thirty-three biliary complications were found in a total of 22 patients, whereas four patients showed normal bile ducts. Anastomotic strictures were evident in 14 (53.8%) patients, non-anastomotic strictures in seven (26.9%), biliary cast in three (11.5%), and stones in six (23.1%). A benefit of cholangioscopy was seen in 12 (46.2%) patients. In four of them, cholangioscopy was crucial for selective guidewire placement prior to planned intervention. In six patients, biliary cast and/or stones failed to be diagnosed by ERCP and were only detectable through cholangioscopy. In one case, a bile duct ulcer due to fungal infection was diagnosed by cholangioscopy. In another case, signs of bile duct inflammation caused by acute cholangitis were evident. One patient developed post-interventional cholangitis. No further procedure-related complications occurred. Thirty-seven isolates were found in bile. Sixteen of these were gram-positive (43.2%), 12 (32.4%) were gram-negative bacteria, and Candida species accounted for 24.3% of all isolated microorganisms. Interestingly, only 48.6% of specimens were sensitive to prophylactic antibiotics.

Conclusion: Single-operator cholangioscopy can provide important diagnostic information, helping endoscopists to plan and perform interventional procedures in LT-related biliary complications.
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http://dx.doi.org/10.3748/wjg.v23.i22.4064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473125PMC
June 2017

Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis.

Crit Care Med 2017 Oct;45(10):1616-1624

1Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Muenster, Muenster, Germany. 2Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany. 3Department of Transplant Medicine, University Hospital Muenster, Muenster, Germany. 4Data Management Center of the EASL-CLIF Consortium, CIBEReHD, Barcelona, Spain. 5Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain. 6Liver Unit, Hospital General Universitario Gregorio Maranon, IiSGM, Madrid, Spain.

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.
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http://dx.doi.org/10.1097/CCM.0000000000002562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598913PMC
October 2017

Molecular adsorbent recirculating system (MARS) in acute liver injury and graft dysfunction: Results from a case-control study.

PLoS One 2017 12;12(4):e0175529. Epub 2017 Apr 12.

Department of Transplant Medicine, University Hospital Muenster, Muenster, Germany.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175529PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389829PMC
April 2017

Synovial chondromatosis of the temporomandibular joint: Immunohistochemical examinations regarding the role of insulin-like growth factors and their binding proteins in the etiology of this disease.

J Craniomaxillofac Surg 2017 Feb 14;45(2):198-202. Epub 2016 Dec 14.

Department of Oral and Maxillofacial and Plastic Surgery (Head: Prof. Dr. Dr. R.H. Reich), University of Bonn, Welschnonnenstraße 17, 53111 Bonn, Germany.

Synovial chondromatosis (SC) is a benign disease of the joints without a known cause. It sometimes affects the temporomandibular joint (TMJ) and is accompanied by pain, swelling, malocclusion, and crepitation. It has been divided into three stages by Milgram and is supposed to originate from the synovia and cartilage of a joint (Milgram, 1977b). The aim of this study was to examine an involvement of the insulin-like growth factors (IGF-I/-II) and their binding proteins (IGFBP-1 to -6) in the etiology of this disease. Therefore 23 specimen of SC from 16 patients were immunohistochemically stained and microscopically examined. Staining was assessed semiquantitatively: negative (-), weakly positive ((+)), moderately positive (+), strongly positive (++) and very strongly positive (+++). It could be seen that especially the chondro- and fibrocytes and the synovia showed positive staining for almost all IGFs and IGFBPs. The underlying tissue, consisting of connective tissue or chondroid matrix, was stained as well but more weakly so. We conclude that the IGF/IGFBP system seems to contribute to the pathogenesis of SC, especially IGF-I and -II, and their effects enhancing binding protein 5.
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http://dx.doi.org/10.1016/j.jcms.2016.12.005DOI Listing
February 2017

Limits of and Complications after Embolization of the Hepatic Artery and Portal Vein to Induce Segmental Hypertrophy of the Liver: A Large Mini-Pig Study.

Eur Surg Res 2016 20;57(3-4):155-170. Epub 2016 Jul 20.

Department of General, Visceral, Thoracic, Transplantation and Pediatric Surgery University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany.

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.
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http://dx.doi.org/10.1159/000447511DOI Listing
April 2017

[Ultrasound of livertransplants].

Dtsch Med Wochenschr 2016 Jul 30;141(13):933-9. Epub 2016 Jun 30.

The overall long-term survival rate of liver transplant patients is 70-75 %. During the early stages, the complications are vascular in nature, and in the later stages, biliary complications are major causes of morbidity. With the help of sonography, in particular with the addition of contrast enhanced ultrasound, a reliable diagnosis is possible. Despite this, in individual cases, other additional imaging methods should still be employed. The therapy should be used exclusively by interventional gastroentologists, radiologists or surgeons.
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http://dx.doi.org/10.1055/s-0042-103977DOI Listing
July 2016

[Long-term-management of organ transplant recipients].

Dtsch Med Wochenschr 2016 Jul 30;141(13):927-32. Epub 2016 Jun 30.

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.
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http://dx.doi.org/10.1055/s-0042-103978DOI Listing
July 2016

Editorial: Determinants of Synaptic Information Transfer: From Ca(2+) Binding Proteins to Ca(2+) Signaling Domains.

Front Cell Neurosci 2016 16;10:69. Epub 2016 Mar 16.

Medical Faculty, Carl-Ludwig Institute for Physiology, University of Leipzig Leipzig, Germany.

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http://dx.doi.org/10.3389/fncel.2016.00069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792874PMC
March 2016

CaRuby-Nano: a novel high affinity calcium probe for dual color imaging.

Elife 2015 Mar 31;4. Epub 2015 Mar 31.

Laboratory of Biomolecules, UPMC Université Paris 06, Ecole Normale Supérieure, Paris, France.

The great demand for long-wavelength and high signal-to-noise Ca(2+) indicators has led us to develop CaRuby-Nano, a new functionalizable red calcium indicator with nanomolar affinity for use in cell biology and neuroscience research. In addition, we generated CaRuby-Nano dextran conjugates and an AM-ester variant for bulk loading of tissue. We tested the new indicator using in vitro and in vivo experiments demonstrating the high sensitivity of CaRuby-Nano as well as its power in dual color imaging experiments.
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http://dx.doi.org/10.7554/eLife.05808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379494PMC
March 2015

Reading out a spatiotemporal population code by imaging neighbouring parallel fibre axons in vivo.

Nat Commun 2015 Mar 9;6:6464. Epub 2015 Mar 9.

Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.

The spatiotemporal pattern of synaptic inputs to the dendritic tree is crucial for synaptic integration and plasticity. However, it is not known if input patterns driven by sensory stimuli are structured or random. Here we investigate the spatial patterning of synaptic inputs by directly monitoring presynaptic activity in the intact mouse brain on the micron scale. Using in vivo calcium imaging of multiple neighbouring cerebellar parallel fibre axons, we find evidence for clustered patterns of axonal activity during sensory processing. The clustered parallel fibre input we observe is ideally suited for driving dendritic spikes, postsynaptic calcium signalling, and synaptic plasticity in downstream Purkinje cells, and is thus likely to be a major feature of cerebellar function during sensory processing.
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http://dx.doi.org/10.1038/ncomms7464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366501PMC
March 2015

Paclitaxel-eluting balloon dilation of biliary anastomotic stricture after liver transplantation.

World J Gastroenterol 2015 Jan;21(3):977-81

Anna Hüsing, Vito R Cicinnati, Susanne Beckebaum, Christian Wilms, Hartmut H Schmidt, Iyad Kabar, Department of Transplant Medicine, University Hospital Münster, 48149 Münster, Germany.

Aim: To investigate the safety and effectiveness of endoscopic therapy with a paclitaxel-eluting balloon (PEB) for biliary anastomotic stricture (AS) after liver transplantation (LT).

Methods: This prospective pilot study enrolled 13 consecutive eligible patients treated for symptomatic AS after LT at the University Hospital of Münster between January 2011 and March 2014. The patients were treated by endoscopic therapy with a PEB and followed up every 8 wk by endoscopic retrograde cholangiopancreatography (ERCP). In cases of re-stenosis, further balloon dilation with a PEB was performed. Follow-up was continued until 24 mo after the last intervention.

Results: Initial technical feasibility, defined as successful balloon dilation with a PEB during the initial ERCP procedure, was achieved in 100% of cases. Long-term clinical success (LTCS), defined as no need for further endoscopic intervention for at least 24 mo, was achieved in 12 of the 13 patients (92.3%). The mean number of endoscopic interventions required to achieve LTCS was only 1.7 ± 1.1. Treatment failure, defined as the need for definitive alternative treatment, occurred in only one patient, who developed recurrent stenosis with increasing bile duct dilatation that required stent placement.

Conclusion: Endoscopic therapy with a PEB is very effective for the treatment of AS after LT, and seems to significantly shorten the overall duration of endoscopic treatment by reducing the number of interventions needed to achieve LTCS.
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http://dx.doi.org/10.3748/wjg.v21.i3.977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299352PMC
January 2015

Endoscopic ultrasound: valuable tool for diagnosis of biliary complications in liver transplant recipients?

Surg Endosc 2015 Jun 27;29(6):1433-8. Epub 2014 Aug 27.

Department of Transplant Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Gebäude A14, 48149, Münster, Germany.

Background: Biliary complications after liver transplantation (LT) are still common and are an important cause of mortality and morbidity. Until now, endoscopic retrograde cholangiopancreatography (ERCP) has been considered the gold standard for diagnosing such complications. The aim of this study was to evaluate the diagnostic yield and therapeutic impact of endoscopic ultrasound (EUS) in the management of biliary complications after LT.

Methods: Thirty-seven liver transplant patients who presented with clinical, biochemical, sonographic, and/or histological evidence of biliary complications, and who first received EUS followed by ERCP, were enrolled into this prospective observational study. Subsequently, we evaluated the value of EUS in detecting and classifying biliary complications after LT.

Results: Thirty-seven biliary complications were detected in 32 patients. Endoscopic ultrasound showed an overall sensitivity and accuracy of 94.6 % each. In cases of biliary cast and ischemic cholangiopathy, EUS was found to be diagnostically superior to ERCP and has had, in these cases, a significant impact on clinical decision-making. However, EUS was less reliable when diagnosing anastomotic strictures.

Conclusion: EUS can complement ERCP to improve diagnosis of biliary complications after LT and help guide treatment strategies to address these complications.
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http://dx.doi.org/10.1007/s00464-014-3820-3DOI Listing
June 2015

Twitching towards the ideal calcium sensor.

Nat Methods 2014 Feb;11(2):139-40

Wolfson Institute for Biomedical Research and in the Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

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http://dx.doi.org/10.1038/nmeth.2814DOI Listing
February 2014

Calcium rubies: a family of red-emitting functionalizable indicators suitable for two-photon Ca2+ imaging.

J Am Chem Soc 2012 Sep 27;134(36):14923-31. Epub 2012 Aug 27.

UPMC Université Paris 06, Ecole Normale Supérieure, Paris, F-75005 France.

We designed Calcium Rubies, a family of functionalizable BAPTA-based red-fluorescent calcium (Ca(2+)) indicators as new tools for biological Ca(2+) imaging. The specificity of this Ca(2+)-indicator family is its side arm, attached on the ethylene glycol bridge that allows coupling the indicator to various groups while leaving open the possibility of aromatic substitutions on the BAPTA core for tuning the Ca(2+)-binding affinity. Using this possibility we now synthesize and characterize three different CaRubies with affinities between 3 and 22 μM. Their long excitation and emission wavelengths (peaks at 586/604 nm) allow their use in otherwise challenging multicolor experiments, e.g., when combining Ca(2+) uncaging or optogenetic stimulation with Ca(2+) imaging in cells expressing fluorescent proteins. We illustrate this capacity by the detection of Ca(2+) transients evoked by blue light in cultured astrocytes expressing CatCh, a light-sensitive Ca(2+)-translocating channelrhodopsin linked to yellow fluorescent protein. Using time-correlated single-photon counting, we measured fluorescence lifetimes for all CaRubies and demonstrate a 10-fold increase in the average lifetime upon Ca(2+) chelation. Since only the fluorescence quantum yield but not the absorbance of the CaRubies is Ca(2+)-dependent, calibrated two-photon fluorescence excitation measurements of absolute Ca(2+) concentrations are feasible.
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http://dx.doi.org/10.1021/ja304018dDOI Listing
September 2012