Publications by authors named "Peter Malfertheiner"

540 Publications

Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib.

Cancer Imaging 2022 Jan 4;22(1). Epub 2022 Jan 4.

Department of Radiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Background: The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment.

Methods: Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS.

Results: The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22-0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS.

Conclusion: OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.
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http://dx.doi.org/10.1186/s40644-021-00439-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725442PMC
January 2022

New Rapid Helicobacter Pylori Blood Test Based on Dual Detection of FliD and CagA Antibodies for On-Site Testing.

Clin Gastroenterol Hepatol 2021 Nov 16. Epub 2021 Nov 16.

Medical Department II, University Hospital, LMU, Munich, Germany; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

Helicobacter pylori is the most prevalent bacterial infection, affecting half of the world's population, with a high morbidity and mortality rate. Several invasive and noninvasive testing procedures are available, and their selective use serves the specific needs of diverse clinical scenarios. For gastric cancer prevention, mass screening is necessary and requires a noninvasive, rapid, accurate and cost-effective test. For this purpose H pylori serology currently seems to be the preferred noninvasive diagnostic method. Population-based testing and treatment for H pylori is cost effective in high-risk countries, but less effective in low- and medium-risk countries. Many serologic tests are available on the market, with inconsistent performance often being observed. Therefore, international guidelines recommend considering only serologic tests with high accuracy that have been validated in the respective local populations. To date, no rapid point-of-care test (POCT) has reached a sufficient degree of accuracy.
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http://dx.doi.org/10.1016/j.cgh.2021.11.008DOI Listing
November 2021

Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

J Gastrointestin Liver Dis 2021 Dec 21;30(4):431-437. Epub 2021 Dec 21.

Magdeburg, Germany.

Background And Aims: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC.

Methods: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire.

Results: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p<0.0001), and were more likely to have Union for International Cancer Control (UICC) stage III-IV (54.1vs. 38.9%, p=0.0034). Especially, dysphagia and weight loss were more common in patients with cardia GC (49.2 vs. 6.4 %, p<0.0001 and 37.1 vs. 25.7%, p=0.02, respectively). No differences between the two groups were observed with respect to reflux symptoms. Patients with alarm symptoms were more likely to have UICC stage III-IV at presentation (69.4 vs. 42.9%, p<0.0001).

Conclusions: In clinical practice the symptom pattern at presentation may serve as a hint for tumor localization. Despite the fact that they are common in the general population, dyspeptic symptoms offer a chance for earlier GC detection. Thus, in patients with dyspeptic symptoms who fail empiric approaches, endoscopy should not be delayed.
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http://dx.doi.org/10.15403/jgld-3795DOI Listing
December 2021

Pazopanib with 5-FU and oxaliplatin as first line therapy in advanced gastric cancer: A randomized phase-II study-The PaFLO trial. A study of the Arbeitsgemeinschaft Internistische Onkologie AIO-STO-0510.

Int J Cancer 2022 Mar 15;150(6):1007-1017. Epub 2021 Nov 15.

Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.

VEGF inhibition in gastric cancer has a proven benefit in the second line setting. Pazopanib, an oral tyrosine kinase inhibitor, selectively inhibits VEGFR-1, -2 and -3, c-kit and PDGF-R resulting in inhibition of angiogenesis. This open-label randomized phase II trial (2:1) investigated the efficacy of combining pazopanib with FLO (5-fluorouracil, oxaliplatin) vs FLO alone (internal control arm) as first-line treatment in patients with advanced adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Eighty-seven patients were randomized and 78 patients were eligible and evaluable (PaFLO arm 51 patients, FLO arm 27 patients). The PFS rate at 6 months (primary endpoint) was 34% in the PaFLO arm vs 30% in the FLO arm. Comparing PaFLO with FLO median PFS was 4.66 months (95% confidence interval [CI] 2.87-6.46) vs 4.47 months (95% CI 1.79-7.14) (95% CI, hazard ratio [HR] 0.96 (0.60-1.55), P = .882 [exploratory]); median OS was 10.19 months (95% CI 5.46-14.92) vs 7.33 months (95% CI 4.93-9.73), (95% CI HR 1.01 [0.62-1.65], P = .953, exploratory), disease control rate was 72% vs 59%. PaFLO was well tolerable, toxicities were slightly higher in the PaFLO arm. Major adverse events were loss of appetite, nausea, fatigue, diarrhea, neutropenia and thrombocytopenia. Adding pazopanib to chemotherapy shows signs of efficacy but no major improvement in this randomized phase 2 trial. The PFS at 6 months in both arms was lower than expected from the literature. Biomarkers identifying subgroups who benefit and novel combinations are needed. ClinicalTrials.gov: NCT01503372.
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http://dx.doi.org/10.1002/ijc.33864DOI Listing
March 2022

Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma.

Br J Cancer 2022 Feb 22;126(2):211-218. Epub 2021 Oct 22.

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Aims: To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC).

Design: Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression.

Results: Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD.

Conclusions: Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.
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http://dx.doi.org/10.1038/s41416-021-01577-6DOI Listing
February 2022

A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Therapy.

Nutrients 2021 Sep 11;13(9). Epub 2021 Sep 11.

Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg Clinic, OVGU University, 39120 Magdeburg, Germany.

() eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in patients of a Test fermented milk containing yogurt and ( CNCM I-1518 and I-3689, CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of and calprotectin, and a decrease of SCFA concentrations. Following treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower ( = 0.02), some , including ( = 0.0082) and ( = 0.013), were less abundant, and concentrations of major SCFA ( = 0.035) and valerate ( = 0.045) were higher. Viable strains were detected during product consumption in feces. Results suggest that, in patients under treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.
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http://dx.doi.org/10.3390/nu13093171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466689PMC
September 2021

Gadoxetic acid uptake as a molecular imaging biomarker for sorafenib resistance in patients with hepatocellular carcinoma: a post hoc analysis of the SORAMIC trial.

J Cancer Res Clin Oncol 2021 Sep 20. Epub 2021 Sep 20.

Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Purpose: Gadoxetic acid uptake on hepatobiliary phase MRI has been shown to correlate with ß-catenin mutation in patients with HCC, which is associated with resistance to certain therapies. This study aimed to evaluate the prognostic value of gadoxetic acid uptake on hepatobiliary phase MRI in patients with advanced HCC receiving sorafenib.

Methods: 312 patients with available baseline hepatobiliary phase MRI images received sorafenib alone or following selective internal radiation therapy (SIRT) within SORAMIC trial. The signal intensity of index tumor and normal liver parenchyma were measured on the native and hepatobiliary phase MRI images, and relative tumor enhancement higher than relative liver enhancement were accepted as high gadoxetic acid uptake, and its prognostic value was assessed using univariate and multivariate Cox proportional hazard models.

Results: The median OS of the study population was 13.4 (11.8-14.5) months. High gadoxetic acid uptake was seen in 51 (16.3%) patients, and none of the baseline characteristics was associated with high uptake. In univariate analysis, high gadoxetic acid uptake was significantly associated with shorter overall survival (10.7 vs. 14.0 months, p = 0.005). Multivariate analysis confirmed independent prognostic value of high gadoxetic acid uptake (HR, 1.7 [1.21-2.3], p = 0.002), as well as Child-Pugh class (p = 0.033), tumor diameter (p = 0.002), and ALBI grade (p = 0.015).

Conclusion: In advanced HCC patients receiving sorafenib (alone or combined with SIRT), high gadoxetic acid uptake of the tumor on pretreatment MRI, a surrogate of ß-catenin mutation, correlates with shorter survival. Gadoxetic acid uptake status might serve in treatment decision-making process.
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http://dx.doi.org/10.1007/s00432-021-03803-3DOI Listing
September 2021

[Prevention of gastrointestinal cancer].

Z Gastroenterol 2021 Sep 10;59(9):964-982. Epub 2021 Sep 10.

II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Universitätsklinikum Mannheim, Mannheim.

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.
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http://dx.doi.org/10.1055/a-1540-7539DOI Listing
September 2021

Correlation of liver enhancement in gadoxetic acid-enhanced MRI with liver functions: a multicenter-multivendor analysis of hepatocellular carcinoma patients from SORAMIC trial.

Eur Radiol 2022 Feb 31;32(2):1320-1329. Epub 2021 Aug 31.

Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Objectives: To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study.

Methods: A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin [ALBI]), and scanner characteristics were analyzed using uni- and multivariate analyses.

Results: There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001).

Conclusions: The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands.

Key Points: • The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. • Signal intensity-based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. • However, absolute values might change between vendors.
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http://dx.doi.org/10.1007/s00330-021-08218-9DOI Listing
February 2022

Impact of healthy aging on active bacterial assemblages throughout the gastrointestinal tract.

Gut Microbes 2021 Jan-Dec;13(1):1966261

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

The adaption of gut microbiota (GM) throughout human life is a key factor in maintaining health. Interventions to restore a healthy GM composition may have the potential to improve health and disease outcomes in the elderly. We performed a comprehensive characterization of changes in the luminal and mucosa-associated microbiota composition in elderly compared with younger healthy individuals. Samples from saliva and feces, and biopsies from the upper and lower gastrointestinal tract (UGIT, LGIT), were collected from 59 asymptomatic individuals grouped by age: 40-55, 56-70, and 71-85 years). All underwent anthropometric, geriatric, and nutritional assessment. RNA was extracted and reverse-transcribed into complementary DNA; the V1-V2 regions of 16S ribosomal RNA genes were amplified and sequenced. Abundances of the taxa in all taxonomic ranks in each sample type were used to construct sample-similarity matrices by the Bray-Curtis algorithm. Significant differences between defined groups were assessed by analysis of similarity. The bacterial community showed strong interindividual variations and a clear distinction between samples from UGIT, LGIT, and feces. While in saliva some taxa were affected by aging, this number was considerably greater in UGIT and was subsequently higher in LGIT. Unexpectedly, aging scarcely influenced the bacterial community of feces over the age range of 40-85 years. The development of interventions to preserve and restore human health with increased age by establishing a healthy gut microbiome should not rely solely on data from fecal analysis, as the intestinal mucosa is affected by more significant changes, which differ from those observed in fecal analyses.
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http://dx.doi.org/10.1080/19490976.2021.1966261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409759PMC
January 2022

Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma.

J Hepatol 2021 12 27;75(6):1387-1396. Epub 2021 Aug 27.

Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain.

Background & Aims: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function.

Methods: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up.

Results: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08).

Conclusion: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy.

Clinical Trial Number: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.
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http://dx.doi.org/10.1016/j.jhep.2021.07.037DOI Listing
December 2021

Gastrointestinal bleeding in patients with Helicobacter pylori and dual platelet inhibition after myocardial infarction.

Lancet Gastroenterol Hepatol 2021 09;6(9):684-685

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany; Department of Medicine II, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.

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http://dx.doi.org/10.1016/S2468-1253(21)00192-8DOI Listing
September 2021

Gut microbiota profiles and the role of anti-CdtB and anti-vinculin antibodies in patients with functional gastrointestinal disorders (FGID).

Eur J Clin Invest 2021 Dec 24;51(12):e13666. Epub 2021 Aug 24.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

Background: Distinct faecal microbiota profiles are reported to be associated with various subtypes of IBS. Circulating antibodies to cytolethal distending toxin B (CdtB) and vinculin are proposed as biomarkers to identify post-infectious IBS. The aim of our study was to analyse serum levels of anti-CdtB and anti-vinculin antibodies in patients with different functional gastrointestinal disorders (FGID) and their correlation with the composition of faecal microbiome.

Methods: The study cohort comprised 65 prospectively recruited individuals: 15 with diarrhoea-type-IBS (IBS-D), 13 with constipation-type-IBS (IBS-C), 15 with functional dyspepsia (FD) and 22 healthy controls. FGID subgroups were defined according to Rome III criteria. Serum levels of anti-CdtB and anti-vinculin antibodies were measured by ELISA. Faecal microbiome composition analysis and assessment of dysbiosis were performed by GA-map® Dysbiosis Test.

Results: Positivity rate either for anti-CdtB or anti-vinculin antibodies was higher in the IBS-C group (76.9%) compared to IBS-D (40.0%), FD (60%) and healthy (63.6%) groups. Dysbiosis was more frequent in subjects positive for anti-CdtB antibodies and in IBS-C patients, who showed an increased amount of opportunistic/pro-inflammatory bacteria and reduced gut protective bacteria. IBS-C patients showed a high inter-individual variation of bacterial communities compared to other FGID subgroups and healthy individuals, whereas microbial profiles of patients with IBS-D and FD were overlapping with those of healthy controls. No bacteria markers showed significant differences between FGID subgroups and healthy controls.

Conclusion: Neither anti-CdtB/anti-vinculin antibodies nor faecal microbial profiles allowed to discriminate between specific FGID subgroups. Dysbiosis was more frequent in patients presenting with anti-CdtB antibodies and in IBS-C patients.
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http://dx.doi.org/10.1111/eci.13666DOI Listing
December 2021

The Fear of Gastric Cancer in Patients with Dyspepsia: Challenge in Specialist Care Gastroenterology.

Dig Dis 2021 Jul 13. Epub 2021 Jul 13.

Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.

Background: Dyspepsia is one of the most common complaints in gastroenterology. While its etiology is usually benign, rare cases of malignancy have to be identified. Individualized risk stratification is essential for cost-effective management of dyspepsia. Here, we discuss the challenges of investigating dyspepsia at the specialist level and provide a framework for rational workup and surveillance strategies.

Summary: Causes of dyspepsia can be functional or organic, including gastritis, peptic ulcers, or malignancy. H. pylori gastritis represents a specific entity of dyspepsia and increases the risk of gastric cancer. H. pylori eradication can improve symptoms in a subset of patients and reduce gastric cancer risk. In young patients without alarm features, malignancy is rare, and noninvasive testing for H. pylori is appropriate. In elder patients and those with alarm features, high-quality endoscopy is the method of choice to rule out malignancy. Advanced corpus-predominant atrophic gastritis with or without intestinal metaplasia represent precancerous lesions. Key Messages: Symptom assessment requires to distinguish dyspepsia of functional or organic origin. Risk stratification in dyspeptic patients is based on age, alarm features, and H. pylori status. Noninvasive test-and-treat is recommended in patients with low gastric cancer risk, while endoscopy is recommended in individuals at increased risk. H. pylori infection should be eradicated in order to obtain a symptomatic benefit and reduce gastric cancer risk. Advanced preneoplastic lesions require endoscopic surveillance.
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http://dx.doi.org/10.1159/000518394DOI Listing
July 2021

[Update 2021: COVID-19 from the perspective of gastroenterology].

Dtsch Med Wochenschr 2021 Jul 13;146(13-14):891-893. Epub 2021 Jul 13.

During COVID 19 pandemic patients typically present with respiratory symptoms. However, in a significant number of patients the gastrointestinal tract is also involved in the disease. Up to 20 % of patients suffering from gastrointestinal symptoms. New insights in pathophysiological aspects might open new therapeutic concepts. This up-date includes current data regarding epidemiology of gastrointestinal symptoms in COVID 19, its role for prognosis and specific risks in relation to immunosuppressive therapies and underlying diseases.
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http://dx.doi.org/10.1055/a-1449-4054DOI Listing
July 2021

Cost-effectiveness modelling of use of urea breath test for the management of -related dyspepsia and peptic ulcer in the UK.

BMJ Open Gastroenterol 2021 07;8(1)

Department of Gastroenterology, Otto-von-Guericke University Hospital, Magdeburg, Germany.

Objective: Clinical data comparing diagnostic strategies in the management of -associated diseases are limited. Invasive and noninvasive diagnostic tests for detecting infection are used in the clinical care of patients with dyspeptic symptoms. Modelling studies might help to identify the most cost-effective strategies. The objective of the study is to assess the cost-effectiveness of a 'test-and-treat' strategy with the urea breath test (UBT) compared with other strategies, in managing patients with -associated dyspepsia and preventing peptic ulcer in the UK.

Design: Cost-effectiveness models compared four strategies: 'test-and-treat' with either UBT or faecal antigen test (FAT), 'endoscopy-based strategy' and 'symptomatic treatment'. A probabilistic cost-effectiveness analysis was performed using a simulation model in order to identify probabilities and costs associated with relief of dyspepsia symptoms (over a 4-week time horizon) and with prevention of peptic ulcers (over a 10-year time horizon). Clinical and cost inputs to the model were derived from routine medical practice in the UK.

Results: For relief of dyspepsia symptoms, 'test-and-treat' strategies with either UBT (€526/success) and FAT (€518/success) were the most cost-effective strategies compared with 'endoscopy-based strategy' (€1317/success) and 'symptomatic treatment' (€1 029/success). For the prevention of peptic ulcers, 'test-and-treat' strategies with either UBT (€208/ulcer avoided/year) or FAT (€191/ulcer avoided/year) were the most cost-effective strategies compared with 'endoscopy-based strategy' (€717/ulcer avoided/year) and 'symptomatic treatment' (€651/ulcer avoided/year) (1 EUR=0,871487 GBP at the time of the study).

Conclusion: 'Test-and-treat' strategies with either UBT or FAT are the most cost-effective medical approaches for the management of -associated dyspepsia and the prevention of peptic ulcer in the UK. A 'test-and-treat' strategy with UBT has comparable cost-effectiveness outcomes to the current standard of care using FAT in the UK.
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http://dx.doi.org/10.1136/bmjgast-2021-000685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268888PMC
July 2021

NMR-Based Lipid Metabolite Profiles to Predict Outcomes in Patients Undergoing Interventional Therapy for a Hepatocellular Carcinoma (HCC): A Substudy of the SORAMIC Trial.

Cancers (Basel) 2021 Jun 3;13(11). Epub 2021 Jun 3.

Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany.

Background: This exploratory study aimed to evaluate lipidomic and metabolomic profiles in patients with early and advanced HCCs and to investigate whether certain metabolic parameters may predict the overall survival in these patients.

Methods: A total of 60 patients from the prospective, randomized-controlled, multicenter phase II SORAMIC trial were included in this substudy; among them were 30 patients with an early HCC who underwent radiofrequency ablation combined with sorafenib or a placebo and 30 patients with an advanced HCC who were treated with a selective internal radiation therapy (SIRT) plus sorafenib vs. sorafenib alone. The blood serum of these patients was analyzed using a standardized nuclear magnetic resonance (NMR) platform. All tested metabolites were correlated with the overall survival.

Results: The overall survival (OS) was significantly higher in patients with an early HCC (median OS: 34.0 months) compared with patients with an advanced HCC (median OS: 12.0 months) ( < 0.0001). Patients with high serum concentrations of myo-inositol (MI) had a higher overall survival compared with patients with low concentrations (21.6 vs. 13.8 months) with a Pearson correlation coefficient of 0.331 ( = 0.011). Patients with high serum concentrations of dimethylamine had a higher overall survival compared with patients with low concentrations (25.1 vs. 19.7 months) with a Pearson correlation coefficient of 0.279 ( = 0.034). High concentrations of total cholesterol, LDL-cholesterol and LDL particles (LDL-P) were associated with a decreased overall survival.

Conclusions: NMR-based lipidomic and metabolomic profiling has the potential to identify individual metabolite biomarkers that predict the outcome of patients with an HCC exposed to non-invasive therapeutic management.
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http://dx.doi.org/10.3390/cancers13112787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199928PMC
June 2021

Prognostic value of baseline interleukin 6 levels in liver decompensation and survival in HCC patients undergoing radioembolization.

EJNMMI Res 2021 Jun 2;11(1):51. Epub 2021 Jun 2.

Department of Radiology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Background: To confirm the prognostic value of previously published baseline interleukin 6 (IL6) and IL8 cutoff values in survival and liver dysfunction in patients with advanced HCC undergoing Y radioembolization.

Methods: A total of 83 patients (77 male) represented a subset of HCC patients undergoing Y radioembolization combined with sorafenib as part of the prospective multicenter phase II trial SORAMIC. IL6 and IL8 levels were determined in serum samples collected at baseline. In this post hoc analysis, we sought to confirm the prognostic value of baseline cutoff values of 6.53 pg/mL and 60.8 pg/mL for IL6 and IL8, respectively, in overall survival (OS) or liver dysfunction (grade 2 bilirubin increase) after treatment.

Results: Median OS was 12.0 months. While low baseline albumin and high bilirubin values were associated with high IL6, liver cirrhosis, alcoholic liver disease, and portal vein infiltration were associated with high IL8. In univariate analysis, high baseline IL6 and IL8 were associated with significantly shorter overall survival (7.8 vs. 19.0 months for IL6 and 8.4 vs. 16.0 months for IL8). In addition to IL values, liver cirrhosis, Child-Pugh grade, baseline albumin (< 36 g/dL), and total bilirubin (≥ 17 µmol/L), and higher mALBI grade (2b &3) values were associated with OS. At multivariate analysis, high baseline IL6 was the only independent prognostic factor for OS (HR 2.35 [1.35-4.1], p = 0.002). Risk factors for liver dysfunction were high baseline IL6, albumin, and total bilirubin, and mALBI grade as found in univariate analysis. High baseline IL6 (HR 2.67 [1.21-5.94], p = 0.016) and total bilirubin ≥ 17 µmol/L (HR 3.73 [1.72-8.06], p < 0.001) were independently associated with liver dysfunction.

Conclusion: In advanced HCC patients receiving Y radioembolization combined with sorafenib, baseline IL6 values proved to be prognostic, confirming previous findings in patients undergoing Yradioembolization. IL6 might be useful for patient selection or stratification in future trials.
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http://dx.doi.org/10.1186/s13550-021-00791-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172845PMC
June 2021

EGF and BMPs Govern Differentiation and Patterning in Human Gastric Glands.

Gastroenterology 2021 08 3;161(2):623-636.e16. Epub 2021 May 3.

Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany; Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. Electronic address:

Background & Aims: The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organized inside glands and crypts. Regeneration depends on Wnt/β-catenin pathway activation, but to understand homeostasis and its dysregulation in disease, we need to identify the signaling microenvironment governing cell differentiation. By using gastric glands as a model, we have identified the signals inducing differentiation of surface mucus-, zymogen-, and gastric acid-producing cells.

Methods: We generated mucosoid cultures from the human stomach and exposed them to different growth factors to obtain cells with features of differentiated foveolar, chief, and parietal cells. We localized the source of the growth factors in the tissue of origin.

Results: We show that epidermal growth factor is the major fate determinant distinguishing the surface and inner part of human gastric glands. In combination with bone morphogenetic factor/Noggin signals, epidermal growth factor controls the differentiation of foveolar cells vs parietal or chief cells. We also show that epidermal growth factor is likely to underlie alteration of the gastric mucosa in the precancerous condition atrophic gastritis.

Conclusions: Use of our recently established mucosoid cultures in combination with analysis of the tissue of origin provided a robust strategy to understand differentiation and patterning of human tissue and allowed us to draw a new, detailed map of the signaling microenvironment in the human gastric glands.
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http://dx.doi.org/10.1053/j.gastro.2021.04.062DOI Listing
August 2021

Inflammatory microRNAs in gastric mucosa are modulated by Helicobacter pylori infection and proton-pump inhibitors but not by aspirin or NSAIDs.

PLoS One 2021 15;16(4):e0249282. Epub 2021 Apr 15.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.

Gastric carcinogenesis is associated with alterations of microRNAs (miRNAs) and reversal of these alterations may be a crucial element in cancer prevention. Here we evaluate the influence of H. pylori eradication, low-dose aspirin (LDA), non-steroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPI) on modification of inflammatory mucosal miRNAs miR-155 and miR-223 in Helicobacter pylori-infected and non-infected subjects. The study was performed in two parts: 1) interventional study in 20 healthy subjects with and without H. pylori infection or following eradication (each n = 10) where LDA (100 mg) was given daily for 7 days; 2) prospective case-control observational study (n = 188). MiR-155 and miR-223 expression was strongly linked to H. pylori-infection and in short-term view showed a trend for reversal after eradication. Daily LDA as well as regular NSAIDs showed no influence on miRNAs expression both in healthy subjects and patients, while regular PPI intake was associated with lower miR-155 expression in antrum of patients with chronic gastritis independent of density of neutrophils and mononuclear infiltrate. In summary, PPI but not LDA or NSAIDs were associated with modification of inflammatory miRNAs miR-155 and miR-223 in an H. pylori dependent manner. The functional role of inflammatory miR-155 and miR-223 in understanding of H. pylori-related diseases needs further evaluation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249282PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049315PMC
September 2021

Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial.

J Cancer Res Clin Oncol 2021 Apr 14. Epub 2021 Apr 14.

Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Purpose: To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib.

Methods: A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response.

Results: Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9-8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2-4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22-7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02-4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011).

Conclusion: IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.
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http://dx.doi.org/10.1007/s00432-021-03627-1DOI Listing
April 2021

Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: A Network Meta-analysis.

Gastroenterology 2021 08 8;161(2):495-507.e4. Epub 2021 Apr 8.

Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas.

Background & Aims: A number of double, triple, and quadruple therapies have been proposed as first-line empiric treatments for Helicobacter pylori infection. However, knowledge of their worldwide and regional comparative efficacy is lacking. We examined the comparative effectiveness of all empirically used first-line regimens tested against standard triple treatment using a network meta-analysis of published randomized controlled trials.

Methods: Data extracted from eligible randomized controlled trials were entered into a Bayesian network meta-analysis to investigate the comparative efficacy of H pylori infection empiric first-line regimens and to explore their effectiveness rank order. The ranking probability for each regimen was evaluated by means of surfaces under cumulative ranking values.

Results: Sixty-eight eligible randomized controlled trials were included, giving a total of 92 paired comparisons with 22,975 patients randomized to 8 first-line regimens. The overall results showed that only vonoprazan triple therapy and reverse hybrid therapy achieved cure rates of >90%. Levofloxacin triple therapy performed best in Western countries (eradication rate 88.5%). The comparative effectiveness ranking showed that vonoprazan triple therapy had the best results, whereas standard triple therapy was the least efficacious regimen (surfaces under cumulative ranking 92.4% vs 4.7% respectively; odds ratio, 3.80; 95% credible interval, 1.62-8.94).

Conclusions: For first-line empiric treatment of H pylori infection, vonoprazan triple therapy and reverse hybrid therapy achieved high eradication rates of >90%. Levofloxacin triple therapy achieved the highest eradication rates in Western countries. Standard triple therapy was the least efficacious regimen in this network meta-analysis.
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http://dx.doi.org/10.1053/j.gastro.2021.04.012DOI Listing
August 2021

Gastritis: The clinico-pathological spectrum.

Dig Liver Dis 2021 Oct 28;53(10):1237-1246. Epub 2021 Mar 28.

Department of Internal Medicine II, Ludwig Maximilian University Hospital, Munich, Germany.

The inflammatory spectrum of gastric diseases includes different clinico-pathological entities, the etiology of which was recently established in the international Kyoto classification. A diagnosis of gastritis combines the information resulting form the gross examination (endoscopy) and histology (microscopy). It is important to consider the anatomical/functional heterogeneity of the gastric mucosa when obtaining representative mucosal biopsy samples. Gastritis includes self-limiting and non-self-limiting (long-standing) inflammatory diseases, and the latter are epidemiologically, biologically and clinically linked to the onset of gastric cancer (i.e. "inflammation-associated cancer"). Different biological models of inflammation-associated gastric oncogenesis have been proposed. Helicobacter pylori (H. pylori) gastritis is the most prevalent worldwide, and H. pylori is classified as a first-class carcinogen. On these bases, eradicating H. pylori is mandatory for the primary prevention of gastric cancer. Non-self-limiting gastritis may also be triggered by the immune-mediated destruction of gastric parietal cells, resulting in autoimmune gastritis. In both H. pylori-related and autoimmune gastritis, the non-self-limiting inflammation results in atrophy of the gastric mucosa, which is the main factor promoting gastric cancer. Long-term follow-up studies consistently demonstrate the prognostic impact of the histological staging of gastritis in gastric cancer secondary prevention strategies.
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http://dx.doi.org/10.1016/j.dld.2021.03.007DOI Listing
October 2021

Circulating Cell-Free DNA Combined to Magnetic Resonance Imaging for Early Detection of HCC in Patients with Liver Cirrhosis.

Cancers (Basel) 2021 Jan 29;13(3). Epub 2021 Jan 29.

Department of Radiology, University Hospital, LMU Munich, 81377 Munich, Germany.

Liquid biopsy based on circulating cell-free DNA (cfDNA) is a promising non-invasive tool for the prognosis of hepatocellular cancer (HCC). In this exploratory study we investigated whether cfDNA and gene variants associated with HCC may be found in patients with liver cirrhosis (LC) and thus identify those at an increased risk for HCC. A cohort of 40 LC patients with no suspect neoplastic lesions was included in this study. Next generation sequencing (NGS) of cfDNA isolated from plasma was performed on a panel of 597 selected genes. Images of the patients who underwent MRI with hepatospecific contrast media during the study period were retrospectively re-evaluated (imaging was not part of the prospective study). cfDNA was detected in the plasma of 36 patients with LC. NGS-based analyses identified 20 variants in different combinations. Re-evaluation of the MRI images that were available for a proportion of the patients ( = 27) confirmed the absence of lesions in 8 cases carrying cfDNA without variants. In 6 of 19 patients with identified variants and MRI images available, MRI revealed a precursor lesion compatible with HCC and new lesions were discovered at follow-up in two patients. These precursor lesions were amenable for curative treatments. Mutation analysis revealed selective HCC related gene mutations in a subset of patients with LC, raising the suspect that these patients were at an increased risk for HCC development. MRI findings confirmed suspect nodular lesions of early stage HCC not detected with current standard screening procedures, which were only seen in patients carrying cfDNA variants. This opens a perspective for an HCC screening strategy combining both liquid biopsy and MRI in patients with LC.
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http://dx.doi.org/10.3390/cancers13030521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866376PMC
January 2021

The Role of Sphere Size in the Context of Pancreatin Therapy for Exocrine Pancreatic Insufficiency: A Systematic Review.

J Gastrointestin Liver Dis 2021 Mar 12;30(1):132-141. Epub 2021 Mar 12.

University of Leipzig, Medical Faculty, Leipzig, Germany.

While lipase content and appropriate acid protection of pancreatin preparations (PP) are well defined determinants of an effective therapy of exocrine pancreatic insufficiency, the optimal sphere size of PP has remained a matter of discussion. We performed a systematic review to assess the optimal sphere size of enteric coated pancreatin products that may best guarantee coordinated delivery of PP and food to the duodenum. PubMed was searched for studies on gastric emptying of indigestible spheres in the digestive phase, using overlapping search algorithms; identified sources were searched for further leads, extending the investigation to Google Scholar. Of 739 screened publications, 26 were included in the final assessment. Contrary to current guideline recommendations, no scientific evidence was found to support a 2 mm diameter threshold for gastric emptying of indigestible particles. There is no documented advantage of ≤2 mm spheres regarding duodenal delivery and restoring maldigestion. The evolving picture is that of a gradation of sizes, over which gastric emptying becomes slower and more variable as particle size increases. Even 7 mm particles may be emptied from the stomach in conjunction with nutrient uptake. In conclusion sphere size of PP is not the essential parameter for selecting an effective PP fitting all patients. A variety of brands offer different lipase contents and sphere sizes that allow the physician to tailor treatment to the individual patient`s needs.
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http://dx.doi.org/10.15403/jgld-2985DOI Listing
March 2021

Impact of Extrahepatic Metastases on Overall Survival in Patients with Advanced Liver Dominant Hepatocellular Carcinoma: A Subanalysis of the SORAMIC Trial.

Liver Cancer 2020 Dec 11;9(6):771-786. Epub 2020 Nov 11.

Department of Radiology, Hospital of the Ludwig Maximilian University of Munich, Munich, Germany.

Introduction: Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival.

Objective: To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT).

Methods: SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival.

Results: In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, = 11; adrenal glands, = 5; peritoneum, = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively ( = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, = 0.0060).

Conclusions: This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution.
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http://dx.doi.org/10.1159/000510798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768116PMC
December 2020

Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis.

Genes (Basel) 2020 12 15;11(12). Epub 2020 Dec 15.

Department of Gastroenterology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania.

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of rs3200401 CT genotype had the significantly higher odds of atrophic gastritis than those with CC genotype (OR-1.81; 95% CI 1.17-2.80, = 0.0066). Higher odds of AG were found in a recessive model (CC vs. TT + CT) for rs1333045 (OR-1.88; 95% CI 1.19-2.95, = 0.0066). Carriers of (rs17694493) GG genotype had higher odds of gastric cancer (OR-4.93; 95% CI 1.28-19.00) and atrophic gastritis (OR-5.11; 95% CI 1.10-23.80) compared with the CC genotype, and carriers of rs17840857 TG genotype had higher odds of atrophic gastritis (OR-1.61 95% CI 1.04-2.50) compared with the TT genotype; however, the ORs did not reach the adjusted significance threshold ( < 0.007). In summary, our data provide novel evidence for a possible link between lncRNA SNPs and premalignant condition of gastric cancer, suggesting the involvement of lncRNAs in gastric cancer development.
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http://dx.doi.org/10.3390/genes11121505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765138PMC
December 2020

Circulating miR-21-5p level has limited prognostic value in patients with hepatocellular carcinoma and is influenced by renal function.

World J Hepatol 2020 Nov;12(11):1031-1045

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg 39120, Germany.

Background: MicroRNAs (miRNAs) have been suggested as biomarkers for malignant diseases including hepatocellular carcinoma (HCC). Specifically, hsa-miR-21-5p (miR-21) is among the most frequently deregulated miRNA in cancer. The diagnostic and prognostic value of miR-21 has been demonstrated in HCC tissue, mostly in the Asian population. Although the impact of various factors has been recently reported for circulating hsa-miR-122-5p (miR-122), at present only limited knowledge is available for miR-21.

Aim: To evaluate the value of miR-21 for the assessment of prognosis in HCC patients and to delineate the influence of clinical and preanalytical factors on miR-21 level in sera.

Methods: Patients with confirmed HCC from our European cohort with predominantly alcohol-associated liver damage were included in the study. All subjects were characterized according to their clinical and laboratory work-up and overall survival data were obtained. Quantitative real-time polymerase chain reaction was performed for miR-21 and spiked-in cel-miR-39-3p. The results were compared to previously reported miR-122 data.

Results: Survival of HCC patients was comparable between patients with low and high serum miR-21 concentration. No association was observed between miR-21 level in sera and Child-Pugh score, Barcelona Clinic Liver Cancer staging system, or etiology of HCC/liver disease. Age, gender, or pretreatment had no association with miR-21 level. A positive correlation was observed between miR-21 and aspartate aminotransferase ( = 0.2854, = 0.0061), serum miR-122 ( = 0.2624, = 0.0120), and the International Normalized Ratio ( = 0.2065, = 0.0496). Negative correlation of miR-21 with serum creatinine ( = -0.2215, = 0.0348) suggests renal function as a potential influencing factor in miR-21 biogenesis in blood.

Conclusion: The results from this work do not support clinically relevant prognostic value of circulating miR-21 in HCC patients in real-life settings. Following systematic evaluation, we identified renal function and aspartate aminotransferase as potential factors that may affect miR-21 concentration in blood. This knowledge should be considered in future miRNA-based biomarker studies not only for HCC but also for other diseases.
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http://dx.doi.org/10.4254/wjh.v12.i11.1031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701966PMC
November 2020

European Registry on Helicobacter pylori management: Single-capsule bismuth quadruple therapy is effective in real-world clinical practice.

United European Gastroenterol J 2021 02 11;9(1):38-46. Epub 2021 Feb 11.

Department of Gastroenterology, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM) and Centro de Investigación Biomódica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.

Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation.

Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy.

Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line.

Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases.

Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile.
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http://dx.doi.org/10.1177/2050640620972615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259339PMC
February 2021

COVID-19 and Gastrointestinal Disease: Implications for the Gastroenterologist.

Dig Dis 2021 9;39(2):119-139. Epub 2020 Oct 9.

Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, United Kingdom.

Background: COVID-19 was initially considered a respiratory disease but the SARS-CoV-2 virus can lead to serious systemic consequences affecting major organs including the digestive system.

Summary: This review brings new clinically important information for the gastroenterologist. This includes: the mechanisms of tissue damage seen with the SARS-CoV-2 virus; the consequences of immunosuppression in patients with inflammatory bowel disease (IBD) and chronic liver disease with the additional risks of decompensation in patients with cirrhosis; the impact of COVID-19 on gastrointestinal emergencies, on gastrointestinal endoscopy, diagnosis and treatments. These highlight the need to understand the clinical pharmacology, toxicology and therapeutic implications of drugs commonly used by gastroenterologists and their links with COVID-19. Key Messages: Any part of the digestive system may be affected by the SARS-CoV-2 virus, and those with pre-existing disease are at greatest risk of adverse outcomes. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who often require mechanical ventilation and life support. Some repurposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19-related gastrointestinal symptoms and can also induce liver injury. Ongoing clinical studies will hopefully identify effective drugs with a more favourable risk-benefit ratio than many initially tried treatments.
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http://dx.doi.org/10.1159/000512152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705947PMC
April 2021
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