Publications by authors named "Christian Strassburg"

269 Publications

Ruxolitinib for treatment of polycythemia vera and myelofibrosis in patients after liver transplantation.

Clin Case Rep 2021 Sep 5;9(9):e04782. Epub 2021 Sep 5.

Department of Internal Medicine I Rheinische Friedrich-Wilhelms University Bonn Bonn Germany.

Although ruxolitinib contributes to immunomodulation and can lead to severe infections, it seems a feasible treatment strategy for patients with polycythemia vera and myelofibrosis after liver transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.4782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418679PMC
September 2021

Extrahepatic Surgery in Cirrhosis Significantly Increases Portal Pressure in Preclinical Animal Models.

Front Physiol 2021 20;12:720898. Epub 2021 Aug 20.

Department of Internal Medicine 1, Center for Cirrhosis and Portal Hypertension Bonn (CCB), University Hospital Bonn, Bonn, Germany.

Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model. Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured . Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed. Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model. In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.720898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418541PMC
August 2021

Role of circulating angiogenin levels in portal hypertension and TIPS.

PLoS One 2021 25;16(8):e0256473. Epub 2021 Aug 25.

Department of Internal Medicine 1, University Hospital, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

Background: Pathogenesis of portal hypertension is multifactorial and includes pathologic intrahepatic angiogenesis, whereby TIPS insertion is an effective therapy of portal hypertension associated complications. While angiogenin is a potent contributor to angiogenesis in general, little is known about its impact on TIPS function over time.

Methods: In a total of 118 samples from 47 patients, angiogenin concentrations were measured in portal and inferior caval vein plasma at TIPS insertion (each blood compartment n = 23) or angiographic intervention after TIPS (each blood compartment n = 36) and its relationship with patient outcome was investigated.

Results: Angiogenin levels in the inferior caval vein were significantly higher compared to the portal vein (P = 0.048). Ten to 14 days after TIPS, inferior caval vein angiogenin level correlated inversely with the portal systemic pressure gradient (P<0.001), measured invasively during control angiography. Moreover, patients with TIPS revision during this angiography, showed significantly lower angiogenin level in the inferior caval vein compared to patients without TIPS dysfunction (P = 0.01).

Conclusion: In cirrhosis patients with complications of severe portal hypertension, circulating levels of angiogenin are derived from the injured liver. Moreover, angiogenin levels in the inferior caval vein after TIPS may predict TIPS dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256473PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386873PMC
August 2021

US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany.

Int J Hyperthermia 2021 09;38(2):65-74

Department of Diagnostic and Interventional Radiology, University Hospital Bonn, University Bonn, Bonn, Germany.

Introduction: High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect.

Material And Methods: A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients.

Results: An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up ( < .001) for both tumor entities demonstrating effective treatment outcome.

Conclusion: Tumor ablation with HIFU induces an early sterile inflammation that might serve as a precondition for long-term tumor immunity and a sustainable therapeutic effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02656736.2021.1900926DOI Listing
September 2021

Early detection of duodenal cancer by upper gastrointestinal-endoscopy in Lynch syndrome.

Int J Cancer 2021 Jul 31. Epub 2021 Jul 31.

Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.

Small bowel cancer (SBC) is the malignancy with the highest standardized incidence ratio in Lynch syndrome (LS) patients. Of all SBCs, about 50% are duodenal cancers (DCs), therefore being accessible by esophago-gastro-duodenoscopy (EGD) for surveillance. We asked whether early detection of DC is possible for LS patients undergoing surveillance by EGD and if surveillance should be limited to specific subgroups. Data for LS patients with DC were retrieved from the registry of the German Consortium for Familial Intestinal Cancer. Patients undergoing active surveillance by EGDs (surveillance group) were compared to those who did not (nonsurveillance group) regarding tumor stage at diagnosis. Union for International Cancer Control stages I-IIA were defined as early stage disease and IIB-IV as advanced stage disease. Statistical analysis was performed using Fisher's exact test. Among 2015 patients with pathogenic variants in any mismatch-repair-gene, 47 patients with 49 DCs were identified. In 10% of cases, patients were under 35 years at diagnosis; family and personal tumor history did not correlate with DC diagnosis. Pathogenic germline variants in MSH6, PMS2 or EPCAM were present in 10% of patients. Statistical analysis could be performed on 13 DC patients in the surveillance group and 14 in the nonsurveillance group. Early detection was possible for 71% of patients in the surveillance group and 29% of patients in the nonsurveillance group (P = .021). Early detection of DC by EGD in LS patients is feasible regardless of family history, mutational status and should start no later than 25 years of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33753DOI Listing
July 2021

Primary sclerosing cholangitis with moderately elevated serum-IgG4 - characterization and outcome of a distinct variant phenotype.

Liver Int 2021 Jul 30. Epub 2021 Jul 30.

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Background And Aims: Immunoglobulin G4-associated cholangitis (IAC) is characterized by distinctly elevated immunoglobulin G4 in serum (sIgG4) and responds well to corticosteroid therapy. Primary Sclerosing Cholangitis (PSC) is a progressive liver disease without causal treatment options usually not responding to immunosuppression. Increased serum levels of sIgG4 in patients with PSC, that do not meet criteria of IAC, have been reported in 10%-25%. Therefore, we aimed to characterize this subgroup of patients in a retrospective, multicenter study.

Methods: sIgG4 values of 289 patients with PSC from three German university hospitals were analysed. Patients with elevated sIgG4 levels were identified and further characterized by clinical and biochemical parameters and by cholangiographic presentation. Clinical endpoints, death and liver transplantation were compared between groups. Parameters associated with outcome were identified with Cox regression analysis.

Results: 14.5% of patients with PSC showed increased sIgG4 levels (PSC-IgG4), presented with significantly higher (P < .02) albumin, aspartate-aminotransferase, bilirubin and alkaline phosphatase and had a significant lower prevalence of a concomitant autoimmune hepatitis (P = .025). Cholangiogram obtained via ERC showed extrahepatic dominant strictures more often in the PSC-IgG4 subgroup (P = .047). The disease severity models Amsterdam-Oxford-Score (P = .018) and Mayo-Risk-Score (P = .025) predicted lower survival rates for the PSC-IgG4 subgroup. Transplant-free survival after first diagnosis of PSC was shorter in patients with elevated sIgG4 (11.6 vs 15.1 years, P = .001).

Conclusion: Patients with PSC and elevated sIgG4 should be considered as a distinct subgroup, characterized by different clinical and cholangiographical features and are associated with an inferior outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15028DOI Listing
July 2021

Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.

Cancers (Basel) 2021 Jul 5;13(13). Epub 2021 Jul 5.

Department of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany.

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 10 Ad-mAFP-transduced DC were inoculated s.c. followed by 10 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4-, CD8-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13133375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269346PMC
July 2021

Elective Surgery but not Transjugular Intrahepatic Portosystemic Shunt Precipitates Acute-On-Chronic Liver Failure.

Hepatol Commun 2021 Jul 26;5(7):1265-1277. Epub 2021 Mar 26.

Department of Internal Medicine I University of Bonn Bonn Germany.

Acute-on-chronic liver failure (ACLF) is a syndrome associated with organ failure and high short-term mortality. Presence of ACLF at interventions, such as surgery or transjugular intrahepatic portosystemic shunt (TIPS), has been shown to determine outcome, but those interventions have also been attributed to precipitate ACLF in different studies. However, dedicated investigation for the risk of ACLF development in these interventions, especially in elective settings, has not been conducted. Patients with cirrhosis undergoing elective surgery were propensity score matched and compared to patients receiving TIPS. The primary endpoint was ACLF development within 28 days after the respective procedure. The secondary endpoint was 3-month and 1-year mortality. In total, 190 patients were included. Within 28 days, ACLF developed in 24% of the surgery and 3% of the TIPS cohorts, with the highest ACLF incidence between 3 and 8 days. By day 28 after the procedure, ACLF improved in the TIPS cohort. In both cohorts, patients developing ACLF within 28 days after surgery or TIPS placement showed significantly worse survival than patients without ACLF development at follow-up. After 12 months, mortality was significantly higher in the surgery cohort compared to the TIPS cohort (40% vs. 23%, respectively;  = 0.031). Regression analysis showed a European Foundation Chronic Liver Failure Consortium acute decompensation (CLIF-C AD) score ≥50 and surgical procedure as independent predictors of ACLF development. CLIF-C AD score ≥50, C-reactive protein, and ACLF development within 28 days independently predicted 1-year mortality. Elective surgical interventions in patients with cirrhosis precipitate ACLF development and ultimately death, but TIPS plays a negligible role in the development of ACLF. Elective surgery in patients with CLIF-C AD ≥50 should be avoided, while the window of opportunity would be CLIF-C AD <50.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279462PMC
July 2021

[Development and Implementation of a Nutrition Medicine Strategy to optimize Medical Service for Malnourished Patients at a Tertiary Referral Centre].

Zentralbl Chir 2021 Jun 21;146(3):283-295. Epub 2021 Jun 21.

Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Deutschland.

Background: Malnutrition in hospitalised patients is an important and underestimated problem, with a negative impact on outcome and survival - not only in surgical patients. There is a discrepancy between optimal treatment as defined in relevant guidelines on clinical nutrition and the clinical reality. The Main reason for this discrepancy is the lack of established structures for nutrition medicine as an integral part of clinical routines. The necessary structural development is impaired mainly by the lack of resources, but in isolated cases also by the lack of appreciation of the problem. Therefore, practicability and feasibility with regard to local conditions are pivotal for sustainable improvement in a nutrition strategy in hospitalised patients.

Methods: We describe the institutional and procedural measures taken at a tertiary referral centre to implement a nutrition medicine strategy. The underlying nutrition medicine methodology and definitions are introduced and practical implementation at our centre is illustrated by four examples of ongoing projects.

Results: Using the described systematics, structural changes were implemented at our centre within one year that allowed malnutrition screening, the treatment of patients with complex nutritional care and improvements in the nutritive status of hospitalised patients by ongoing and future project initiatives.

Summary: The successfully implemented structural change at the University Hospital of Bonn described here may serve as a modular example for other hospitals striving to improve clinical nutrition and outcome in hospitalised patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1481-9227DOI Listing
June 2021

A genetic variant in toll-like receptor 5 is linked to chemokine levels and hepatocellular carcinoma in steatohepatitis.

Liver Int 2021 09 27;41(9):2139-2148. Epub 2021 Jun 27.

Department of Internal Medicine I, University Hospital, University of Bonn, Bonn, Germany.

Background & Aims: Bacterial translocation drives liver disease progression. We investigated whether functional genetic variants in toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, affect the risk for hepatocellular carcinoma (HCC).

Methods: Healthy controls (n = 212), patients with alcohol abuse without liver disease (n = 382), and patients from a discovery cohort of alcohol-associated cirrhosis (n = 372 including 79 HCC cases), a validation cohort of alcohol-associated cirrhosis (n = 355 including 132 HCC cases), and a cohort of cirrhosis due to nonalcoholic steatohepatitis (NASH) (n = 145 including 62 HCC cases) were genotyped for the TLR5 rs5744174 and rs5744168 polymorphisms. Chemokine levels were measured by ELISA in patients' sera and supernatants of flagellin-stimulated healthy monocytes.

Results: Frequency of the TLR5 rs5744174 TT genotype was similar in healthy controls (33%), controls with alcohol abuse (34%), and patients with alcohol-associated cirrhosis in the discovery (28%), validation (33%), and NASH cohort (31%). The TT genotype was enriched in patients with versus without HCC in the discovery, validation, and NASH cohort (41% vs 25%; 39% vs 29%; 40% vs 24%; p < .05 each). This genotype remained a risk factor for HCC (OR = 1.9; p = .01) after multivariate correction for age, gender, diabetes, and carriage of the PNPLA3 148M variant. Interleukin-8 induction in monocytes from healthy controls and serum levels of interleukin-8 and CXCL1 from cirrhotic patients with the TT genotype were significantly increased versus C allele carriers.

Conclusion: The TLR5 rs5744174 polymorphism, affecting immune response to flagellin, is linked to occurrence of HCC in cirrhosis caused by steatohepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14980DOI Listing
September 2021

Level of MFAP4 in ascites independently predicts 1-year transplant-free survival in patients with cirrhosis.

JHEP Rep 2021 Jun 29;3(3):100287. Epub 2021 Mar 29.

Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.

Background & Aims: Prognostic models of cirrhosis underestimate disease severity for patients with cirrhosis and ascites. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein linked to hepatic neoangiogenesis and fibrogenesis. We investigated ascites MFAP4 as a predictor of transplant-free survival in patients with cirrhosis and ascites.

Methods: A dual-centre observational study of patients with cirrhosis and ascites recruited consecutively in relation to a paracentesis was carried out. Patients were followed up for 1 year, until death or liver transplantation (LTx). Ascites MFAP4 was tested with the model for end-stage liver disease (MELD-Na), CLIF Consortium Acute Decompensation (CLIF-C AD), and Child-Pugh score in Cox regression models.

Results: Ninety-three patients requiring paracentesis were included. Median ascites MFAP4 was 29.7 U/L [22.3-41.3], and MELD-Na was 19 [16-23]. A low MELD-Na score (<20) was observed in 49 patients (53%). During follow-up, 20 patients died (22%), and 6 received LTx (6%). High ascites MFAP4 (>29.7 U/L) was associated with 1-year transplant-free survival ( = 0.002). In Cox regression, ascites MFAP4 and MELD-Na independently predicted 1-year transplant-free survival (hazard ratio [HR] = 0.97,  = 0.03, and HR = 1.08,  = 0.01, respectively). Ascites MFAP4 and CLIF-C AD also predicted survival independently (HR = 0.96,  = 0.02, and HR = 1.05,  = 0.03, respectively), whereas only ascites MFAP4 did, controlling for the Child-Pugh score (HR = 0.97,  = 0.03, and HR = 1.18,  = 0.16, respectively). For patients with MELD-Na <20, ascites MFAP4 but not ascites protein predicted 1-year transplant-free survival (HR 0.91,  = 0.02, and HR = 0.94,  = 0.17, respectively).

Conclusions: Ascites MFAP4 predicts 1-year transplant-free survival in patients with cirrhosis and ascites. In patients with low MELD-Na scores, ascites MFAP4, but not total ascites protein, significantly predicted 1-year transplant-free survival.

Lay Summary: Patients with cirrhosis who have fluid in the abdomen, ascites, are at an increased risk of death and in need for liver transplantation. Our study identified patients with ascites and a poor prognosis by measuring microfibrillar associated protein 4 (MFAP4), a protein present in the abdominal fluid. Patients with low levels of the MFAP4 protein are at particularly increased risk of death or liver transplantation, suggesting that clinical care should be intensified in this group of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhepr.2021.100287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141937PMC
June 2021

Controlled underdilation using novel VIATORR® controlled expansion stents improves survival after transjugular intrahepatic portosystemic shunt implantation.

JHEP Rep 2021 Jun 3;3(3):100264. Epub 2021 Mar 3.

Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.

Background & Aims: Smaller 8-mm diameter transjugular intrahepatic portosystemic shunts (TIPS) appear to be more beneficial than larger 10-mm TIPS stent-grafts, but lack the ability for secondary dilation in cases of clinical ineffectiveness. Underdilated VIATORR® TIPS stent grafts (VTS) expand passively, whereas novel VIATORR Controlled Expansion (VCX) stent grafts do not. This study evaluated the impact on survival of underdilated VCX compared with VTS in patients with decompensated cirrhosis.

Methods: This was a prospective case-control study including patients with cirrhosis receiving TIPS using 10-mm VCX underdilated to 8 mm. Patients with cirrhosis receiving 10-mm VTS underdilated to 8 mm were matched for age, sex, indication for TIPS, and liver function.

Results: A total of 114 patients (47 VCX, 47 VTS, and 20 fully dilated VCX/VTS) were included. After TIPS implantation, underdilated VCX diameter was 8.0 (7.8-9.2) mm at a median time of 359 (87-450) days, compared with VTS at 9.9 (9.7-10.0) mm ( <0.001). The portosystemic pressure gradient immediately after TIPS procedure and after 7 days did not change significantly in VCX [mean 9.4 (± 0.8) 10.4 (± 0.7) mmHg,  = 0.115). Hospital readmission rates for hepatic encephalopathy were 23% (n = 11) 51% (n = 24) for VCX and VTS ( <0.001), respectively. Patients with VCX had significantly lower rates of large-volume paracentesis (n = 5 [11%] n = 10 [21%],  = 0.017) and heart failure (n = 1 [2%] n = 7 [15%],  = 0.015). One-year mortality for underdilated VCX and VTS was 15% (n = 7) and 30% (n = 14) and, for fully dilated VCX/VTS, was 45% (n = 9) (log-rank  = 0.008), respectively.

Conclusions: This study demonstrated that VCX stent grafts underdilated to 8 mm do not passively expand to nominal diameter and suggests reduced hospital readmissions because of hepatic encephalopathy, uncontrolled ascites, and heart failure, and improved 1-year survival compared with underdilated VTS.

Lay Summary: Transjugular intrahepatic portosystemic shunt (TIPS) improves survival in selected patients with liver cirrhosis and acute variceal bleeding or refractory ascites. Smaller 8-mm diameter TIPS stent grafts appear to improve patient outcome compared with larger 10-mm diameter stent grafts. Novel VIATORR® Controlled Expansion (VCX) stent grafts facilitate safe and stable underdilation to 8 mm of large 10-mm diameter stent grafts with improved patient outcome (survival, hepatic encephalopathy, ascites and heart failure) compared with legacy VIATORR TIPS stent graft (VTS). Thus, the use of underdilated VCX could preserve heart function.

Clinical Trials Registration: The study is registered at Clinicaltrials.govNCT03628807.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhepr.2021.100264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113713PMC
June 2021

No evidence to support the impact of migration background on treatment response rates and cancer survival: a retrospective matched-pair analysis in Germany.

BMC Cancer 2021 May 10;21(1):526. Epub 2021 May 10.

Department of Integrated Oncology, CIO Bonn, Center for Integrated Oncology ABCD, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany.

Methods: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression).

Results: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives.

Conclusion: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08141-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108356PMC
May 2021

Cardiac MRI in Suspected Acute COVID-19 Myocarditis.

Radiol Cardiothorac Imaging 2021 Apr 4;3(2):e200628. Epub 2021 Mar 4.

Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (J.A.L., A.I., N.M., M.R., A.F., D.D., U.A.); Quantitative Imaging Lab Bonn (QILaB) (J.A.L., A.I., N.M., M.R., A.F., D.D.); Department of Internal Medicine II - Cardiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (C.O., S.Z.); Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (M.M., S.S., C.B., C.P.S., J.N.); Department of Internal Medicine III-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (A.H.); Department of Anesthesiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (M.V.); Department of Cardiac Surgery, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (G.D.D.).

COVID-19; coronavirus; myocarditis; cardiac MRI; T1 mapping; T2 mapping.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/ryct.2021200628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098091PMC
April 2021

Fecal microbiota transfer for refractory intestinal graft-versus-host disease - Experience from two German tertiary centers.

Eur J Haematol 2021 Aug 9;107(2):229-245. Epub 2021 Jun 9.

German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Germany.

Rationale: Steroid refractory graft-vs-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD.

Objectives: We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n = 11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing.

Results: Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis-each 3/11 and vomiting-1/11). Stool frequencies and volumes were significantly reduced [pre- vs post-FMT (d14): P < .05, respectively] as well as clear attenuation regarding both grading and staging of sr-GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts toward the donor post-FMT.

Conclusions: In our study, we observed positive effects on sr-GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on beneficial effects of FMT in sr-GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode of action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.13642DOI Listing
August 2021

Advances in the pharmacological management of bacterial peritonitis.

Expert Opin Pharmacother 2021 Aug 21;22(12):1567-1578. Epub 2021 Apr 21.

Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany.

Bacterial peritonitis is an infection with high mortality if not treated immediately. In the absence of an intraabdominal source of infection, bacterial peritonitis may arise in patients with liver cirrhosis, in patients on peritoneal dialysis (PD) for end-stage renal disease or in patients with tuberculosis. In patients with cirrhosis, bacterial peritonitis may trigger acute on chronic liver failure with substantial mortality despite optimal treatment. In patients on PD, peritonitis may make continuation of PD impossible, necessitating the switch to hemodialysis. Recovery from peritonitis and prevention of complications depend on timely pharmacological management. Challenges are the broad microbiological spectrum with growing rates of antimicrobial resistance, the underlying chronic liver or kidney failure and high rates of relapse. The authors provide a review of predisposing conditions, diagnosis, and prevention of bacterial peritonitis with a particular focus on the pharmacological management. Diagnosis of the type of bacterial peritonitis is essential to pharmacological management. In patients with spontaneous bacterial peritonitis, broad-spectrum antibiotics should be given intravenously in conjunction with albumin. In patients on PD, antibiotic therapy should be preferably applied intraperitoneally with empirical coverage of gram-positive and gram-negative bacteria. Secondary peritonitis usually requires surgical or interventional treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14656566.2021.1915288DOI Listing
August 2021

Diagnostic value of magnetic resonance parametric mapping for non-invasive assessment of liver fibrosis in patients with primary sclerosing cholangitis.

BMC Med Imaging 2021 Apr 7;21(1):65. Epub 2021 Apr 7.

Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by bile duct inflammation and destruction, leading to biliary fibrosis and cirrhosis. The purpose of this study was to investigate the utility of T1 and T2 mapping parameters, including extracellular volume fraction (ECV) for non-invasive assessment of fibrosis severity in patients with PSC.

Methods: In this prospective study, patients with PSC diagnosis were consecutively enrolled from January 2019 to July 2020 and underwent liver MRI. Besides morphological sequences, MR elastography (MRE), and T1 and T2 mapping were performed. ECV was calculated from T1 relaxation times. The presence of significant fibrosis (≥ F2) was defined as MRE-derived liver stiffness ≥ 3.66 kPa and used as the reference standard, against which the diagnostic performance of MRI mapping parameters was tested. Student t test, ROC analysis and Pearson correlation were used for statistical analysis.

Results: 32 patients with PSC (age range 19-77 years) were analyzed. Both, hepatic native T1 (r = 0.66; P < 0.001) and ECV (r = 0.69; P < 0.001) correlated with MRE-derived liver stiffness. To diagnose significant fibrosis (≥ F2), ECV revealed a sensitivity of 84.2% (95% confidence interval (CI) 62.4-94.5%) and a specificity of 84.6% (CI 57.8-95.7%); hepatic native T1 revealed a sensitivity of 52.6% (CI 31.7-72.7%) and a specificity of 100.0% (CI 77.2-100.0%). Hepatic ECV (area under the curve (AUC) 0.858) and native T1 (AUC 0.711) had an equal or higher diagnostic performance for the assessment of significant fibrosis compared to serologic fibrosis scores (APRI (AUC 0.787), FIB-4 (AUC 0.588), AAR (0.570)).

Conclusions: Hepatic T1 and ECV can diagnose significant fibrosis in patients with PSC. Quantitative mapping has the potential to be a new non-invasive biomarker for liver fibrosis assessment and quantification in PSC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12880-021-00598-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028226PMC
April 2021

Intensified Endoscopic Evaluation for Biliary Complications After Orthotopic Liver Transplantation.

Ann Transplant 2021 Apr 6;26:e928907. Epub 2021 Apr 6.

Department of Surgery, University Hospital Bonn, Bonn, Germany.

BACKGROUND Biliary complications are common causes of morbidity and mortality after liver transplantation. MATERIAL AND METHODS From 2013 to 2018, 102 whole-organ liver transplantations were conducted in our department. Patients were closely monitored for biliary complication development. In all suspected cases, patients underwent either endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangial drainage. Patients' demographic characteristics, preexisting conditions, and perioperative characteristics, as well as morbidity and mortality, were analyzed. Risk factors for 1-year survival were calculated. RESULTS Of the 102 patients, 43 (42%) experienced biliary complications. In comparison with patients without biliary complications, patients with biliary complications exhibited the following risk factors: underlying liver disease (viral hepatitis; P=0.009), blood group A (P=0.005), and previous abdominal surgery (P=0.037). Neither perioperative characteristics, especially duration of cold ischemia (P=0.86), nor postoperative course differed between patients with and without biliary complications. Risk factors for mortality within 1 year were cirrhosis caused by entities other than viral hepatitis (P=0.017), cardiac comorbidities (P=0.019), re-transplantation (P=0.032), and reduced organ weight (P=0.002). Biliary complications, postoperative hemorrhage, primary nonfunction, and repeated surgery worsened outcome; moreover, serum bilirubin trough in the first 30 days after transplantation might be prognostic for mortality (P=0.043). CONCLUSIONS Biliary complications adversely affect outcome after liver transplantation. Neither frequency nor outcome of biliary complications was improved by intensified endoscopic evaluation. Patients on the waiting list for liver transplants should also be closely monitored for cardiac comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/AOT.928907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035812PMC
April 2021

Tumor Infiltrating Neutrophils Are Frequently Found in Adenocarcinomas of the Biliary Tract and Their Precursor Lesions with Possible Impact on Prognosis.

J Pers Med 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, 53127 Bonn, Germany.

Biliary tract cancer (BTC) is characterized by an intense stromal reaction and a complex landscape of infiltrating immune cells. Evidence is emerging that tumor-infiltrating neutrophils (TINs) have an impact on carcinogenesis and tumor progression. TINs have also been associated with outcomes in various solid malignant tumors but their possible clinical role in BTC is largely unknown. Tissue samples from patients with sporadic BTC ("spBTC" cohort, = 53) and BTC in association with primary sclerosing cholangitis ("PSC-BTC" cohort, = 7) were collected. Furthermore, tissue samples from 27 patients with PSC who underwent liver transplantation ("PSC-LTX" cohort) were investigated. All specimens were assessed for TIN density in invasive and precancerous lesions (biliary intraepithelial neoplasia, BilIN). Most spBTC showed low TIN density (LD, 61%). High TIN density (HD) was detected in 16% of the tumors, whereas 23% were classified as intermediate density (ID); the majority of both HD and ID groups were in T1-T2 tumors (83% and 100%, = 0.012). TIN density in BilIN lesions did not significantly differ among the three groups. The HD group had a mean overall survival (OS) of 53.5 months, whereas the mean OS in the LD and ID groups was significantly shorter (LD 29.5 months vs. ID 24.6 months, log-rank < 0.05). The results of this study underline the possible prognostic relevance of TINs in BTC and stress the complexity of the immune cell landscape in BTC. The prognostic relevance of TINs suggests a key regulator role in inflammation and immune landscape in BTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11030233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004909PMC
March 2021

Beta-trace protein as a potential biomarker of residual renal function in patients undergoing peritoneal dialysis.

BMC Nephrol 2021 03 11;22(1):87. Epub 2021 Mar 11.

Diaverum Deutschland GmbH, Munich, Germany.

Background: Residual renal function is closely linked to quality of life, morbidity and mortality in dialysis patients. Beta-trace protein (BTP), a low molecular weight protein, has been suggested as marker of residual renal function, in particular in patients on hemodialysis. We hypothesized that BTP also serves as a marker of residual renal function in pertioneal dialysis patients.

Methods: In this study 34 adult patients on peritoneal dialysis were included. BTP, creatinine, cystatin C and urea concentrations were analyzed simultaneously in serum and dialysate to calculate renal and peritoneal removal of the analytes.

Results: In peritoneal dialysis patients with residual diuresis, mean serum BTP was 8.16 mg/l (SD ± 4.75 mg/l). BTP correlated inversely with residual diuresis (r = - 0.58, p < 0.001), residual creatinine clearance (Cl) (r = - 0.69, p < 0.001) and total urea clearance (Cl) (r = - 0.56, p < 0.001). Mean peritoneal removal of BTP was 3.36 L/week/1.73m (SD ± 1.38) and mean renal removal 15.14 L/week/1.73m (SD ± 12.65) demonstrating a significant renal contribution to the total removal. Finally, serum BTP inversely correlated with alterations in residual diuresis (r = - 0.41, p = 0.035) and renal creatinine clearance over time (r = - 0.79, p = p < 0.001).

Conclusion: BTP measurement in the serum may be a simple tool to assess residual renal function in peritoneal dialysis patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-021-02287-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953776PMC
March 2021

Renal replacement therapy as bridging-to-recovery in refractory hepatorenal syndrome.

Z Gastroenterol 2021 Apr 25;59(4):331-335. Epub 2021 Feb 25.

Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, Bonn, Germany.

A 50-year-old female patient with cirrhosis due to alcoholic steatohepatitis was referred to our department because of recurrent hepatorenal syndrome (HRS) and hepatic hydrothorax. Clinically, severe anasarca was the leading problem. In contrast to previous episodes, HRS did not respond to standard treatment including terlipressin.Given the severe, refractory hyperhydration, we finally initiated renal replacement therapy (RRT). Subsequently, RRT was performed without severe side effects for more than 100 days. In the meantime, liver function remarkably improved, most probably due to the prolonged abstinence from alcohol. Finally, RRT could be stopped. Since then, our patient has remained in good clinical condition for more than 6 months, with well-compensated Child-Pugh stage A cirrhosis and only mild chronic kidney disease stage III.In conclusion, this case highlights that RRT may be considered in individual cases as bridging therapy in refractory HRS until the liver regenerates due to the absence of damaging mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1369-9859DOI Listing
April 2021

Solid organ transplantation is not a risk factor for COVID-19 disease outcome.

Transpl Int 2021 02 10;34(2):378-381. Epub 2021 Jan 10.

Department of Internal Medicine I, Department of Gastroenterology, Hepatology, Nephrology, Infectiology, Endocrinology and Diabetology, University Hospital Bonn, Bonn, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.13795DOI Listing
February 2021

Improving quality of life in pancreatic cancer patients following high-intensity focused ultrasound (HIFU) in two European centers.

Eur Radiol 2021 Aug 23;31(8):5818-5829. Epub 2021 Jan 23.

Clinic for Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, D-53127, Bonn, Germany.

Objectives: Pancreatic cancer patients often have a high symptom burden, significantly impairing patients' quality of life (QOL). Nevertheless, there are hardly any reports on the impact of high-intensity focused ultrasound (HIFU) on the QOL of treated patients. For the first time, this study evaluated the effect of HIFU on QOL and compared these results in two European centers.

Methods: Eighty patients with advanced pancreatic cancer underwent HIFU (50 in Germany, 30 in Bulgaria). Clinical assessment included evaluation of QOL and symptoms using the EORTC QLQ-C30 questionnaire at baseline and 1, 3, and 6 months after HIFU. Pain intensity was additionally evaluated with the numerical rating score (NRS).

Results: Compared to baseline, global health significantly improved 3 and 6 months after HIFU treatment (p = 0.02). Functional subscales including physical, emotional, and social functioning were considerably improved at 6 months (p = 0.02, p = 0.01, and p = 0.01, respectively) as were leading symptom pain (p = 0.04 at 6 months), fatigue (p = 0.03 at 3 and p = 0.01 at 6 months), and appetite loss (p = 0.01 at 6 months). Moreover, pain intensity measured by NRS revealed effective and strong pain relief at all time points (p < 0.001). Reported effects were independent of tumor stage, metastatic status, and country of treatment.

Conclusions: This study showed that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL by increasing global health and mitigation of physical complaints with a low rate of side effects, independent of the examiner. Therefore, HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease.

Key Points: • In a prospective two-center study, it was shown that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL. • HIFU in pancreatic cancer patients is associated with a low rate of side effects, independent of the performer. • HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07682-zDOI Listing
August 2021

Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

Gut 2021 Jan 21. Epub 2021 Jan 21.

Department of Radiology, Beaujon University Hospital, Clichy, France.

Objective: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.

Design: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.

Results: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.

Conclusion: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2020-323419DOI Listing
January 2021

Regulation of uridine diphosphate-glucuronosyltransferase 1A expression by miRNA-214-5p and miRNA-486-3p.

Epigenomics 2021 Feb 12;13(4):271-283. Epub 2021 Jan 12.

Department of Internal Medicine I, University Hospital Bonn, Bonn 53127, Germany.

This study aimed to identify novel miRNAs (miRs) as regulators of gene expression and to evaluate them as potential risk factors for the development of liver fibrosis/cirrhosis. miRNA target sites in UDP-glucuronosyltransferase 1A (UGT1A) 3'-UTR were predicted and confirmed by luciferase assays, quantitative real-time PCR and western blot using HEK293, HepG2 and Huh7 cells. and miRNA expression were analyzed in cirrhotic patients and a mouse model of alcoholic liver fibrosis. miR-214-5p and miR-486-3p overexpression reduced UGT1A mRNA, protein levels and enzyme activity in HepG2 and Huh7 cells. miR-486-3p was upregulated in cirrhotic patients and fibrotic mice livers, whereas UGT1A mRNA levels were reduced. In conclusion, we identified two novel miRNAs capable to repress UGT1A expression and . Furthermore, miR-486-3p may represent a potential risk factor for the development or progression of liver fibrosis/cirrhosis by means of a reduced UGT1A-mediated detoxification activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/epi-2020-0244DOI Listing
February 2021

Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status.

Cancers (Basel) 2020 Dec 11;12(12). Epub 2020 Dec 11.

Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany.

Hereditary diffuse gastric cancer (HDGC) is an inherited cancer susceptibility syndrome characterized by an elevated risk for diffuse gastric cancer (DGC) and lobular breast cancer (LBC). Some patients fulfilling the clinical testing criteria harbor a pathogenic or germline variant. However, the underlying mechanism for around 80% of the patients with a family or personal history of DGC and LBC has so far not been elucidated. In this cohort study, patients meeting the 2015 HDGC clinical testing criteria were included, and subsequently, sequencing was performed. Of the 207 patients (161 families) in this study, we detected 21 pathogenic or likely pathogenic variants (PV) in 60 patients (28 families) and one PV in two patients from one family. Sixty-eight percent ( = 141) of patients were female. The overall PV detection rate was 18% (29/161 families). Criterion 1 and 3 of the 2015 HDGC testing criteria yielded the highest detection rate of PVs (21% and 28%). PV carriers and patients without proven PV were compared. Risk of gastric cancer (GC) (38/62 61% vs. 102/140 73%) and age at diagnosis (40 ± 13 years vs. 44 ± 12 years) were similar between the two groups. However, GC was more advanced in gastrectomy specimens of patients without PV (81% vs. 26%). LBC prevalence in female carriers of a PV was 20% ( = 8/40). Clinical phenotypes differed strongly between families with the same PV. Emphasis should be on detecting more causative genes predisposing for HDGC and improve the management of patients without a proven pathogenic germline variant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12123726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763201PMC
December 2020

Alteration of contrast enhanced ultrasound (CEUS) of hepatocellular carcinoma in patients with cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS).

Sci Rep 2020 11 26;10(1):20682. Epub 2020 Nov 26.

Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Transjugular intrahepatic portosystemic shunt (TIPS) can treat portal hypertensive complications and modifies hepatic hemodynamics. Modification of liver perfusion can alter contrast enhancement dynamics of liver nodules. This study investigated the diagnostic performance of contrast-enhanced ultrasound (CEUS) to diagnose hepatocellular carcinoma (HCC) in cirrhosis with TIPS. In this prospective monocentric observational study, CEUS was used to characterize focal liver lesions in patients at risk for HCC with and without TIPS. Times of arterial phase hyperenhancement (APHE) und washout were quantified. Perfusion-index (PI) and resistance-index (RI) of hepatic artery and portal venous flow parameters were measured via doppler ultrasonography. Diagnostic gold standard was MRI/CT or histology. This study included 49 liver lesions [23 TIPS (11 HCC), 26 no TIPS (15 HCC)]. 26 were diagnosed as HCC by gold standard. Sensitivity and specificity of CEUS to diagnose HCC with and without TIPS were 93.3% and 100% vs. 90.9% and 93.3%, respectively. APHE appeared significantly earlier in patients with TIPS compared to patients without TIPS. TIPS significantly accentuates APHE of HCC in CEUS. CEUS has good diagnostic performance for diagnosis of HCC in patients with TIPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-77801-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692482PMC
November 2020

Pseudoaneurysm associated haemosuccus pancreaticus - a rare and dangerous disease.

CVIR Endovasc 2020 Nov 19;3(1):82. Epub 2020 Nov 19.

Department of Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: In patients with upper gastrointestinal bleeding and hemorrhage originating from the major duodenal papilla pseudoaneurysm associated haemosuccus pancreaticus (HP) is a rare differential diagnosis which should be considered. Diagnosis may be challenging, as clinical presentation is often unspecific with only intermittent hemorrhage. Treatment of the causal pseudoaneurysm is mandatory and endovascular coil embolization is the suitable first-line management strategy. Until now there are only a very few studies about this clinical picture and its therapeutic options, especially data regarding whether additional fluid embolization is beneficial/necessary in HP is currently lacking.

Case Presentation: We report a case of a 59-year-old male patient with chronic pancreatitis and haemosuccus pancreaticus caused by a pancreatico-arterial fistula with an associated inflammatory pseudoaneurysm of the splenic artery. Initially we sought to embolize the pseudoaneurysm with microcoils. As only one coil could be safely deployed in the pseudoaneurysm we additionally employed tissue adhesive embolization in order to achieve complete occlusion of the pseudoaneurysm as well as the pancretico-arterial fistula. In the presented case inflammatory levels decreased following embolization, possibly linked to a decline in pathologic excretion of elastase and autodigestion. As not only the pseudoaneurysm but also the underlying fistula were occluded, the risk of recurrence may conceivably be reduced.

Conclusions: Diagnosis of HP is difficult and treatment of the causal pseudoaneurysm is mandatory. Endovascular embolization is the suitable first-line management strategy, complete occlusion of the fistula should be considered when possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s42155-020-00178-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674537PMC
November 2020
-->