Publications by authors named "Juozas Kupcinskas"

115 Publications

Liquid Biopsy in Gastric Cancer: Analysis of Somatic Cancer Tissue Mutations in Plasma Cell-Free DNA for Predicting Disease State and Patient Survival.

Clin Transl Gastroenterol 2021 Sep 24;12(9):e00403. Epub 2021 Sep 24.

Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Introduction: Gastric cancer (GC) diagnosis in late stages and high mortality rates are the main issues that require new noninvasive molecular tools. We aimed to assess somatic mutational profiles in GC tissue and plasma cell-free DNA (cfDNA), evaluate their concordance rate, and analyze the role of multilayer molecular profiling to predict disease state and prognosis.

Methods: Treatment-naive GC patient group (n = 29) was selected. Whole exome sequencing (WES) of GC tissue was performed, and a unique 38-gene panel for deep targeted sequencing of plasma cfDNA was developed. Oncoproteins were measured by enzyme-linked immunosorbent assay, and other variables such as tumor mutational burden and microsatellite instability were evaluated using WES data.

Results: The yield of cfDNA was increased 43.6-fold; the integrity of fragments was decreased in GC compared with controls. WES analysis of cancerous tissue and plasma cfDNA (targeted sequencing) mutational profiles revealed 47.8% concordance. The increased quantity of GC tissue-derived alterations detected in cfDNA was associated with worse patients' survival. Analysis of importance of multilayer variables and receiver operating characteristic curve showed that combination of 2 analytes: (i) quantity of tissue matching alterations and (ii) presence of any somatic alteration in plasma cfDNA resulted in area under curve 0.744 when discriminating patients with or without distant metastasis. Furthermore, cfDNA sequence alterations derived from tumor tissue were detected in patients who had even relatively small GC tumors (T1-T2).

Discussion: Our results indicate that quantitative and qualitative cfDNA mutational profile analysis is a promising tool for evaluating GC disease status or poorer prognosis.
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http://dx.doi.org/10.14309/ctg.0000000000000403DOI Listing
September 2021

Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk.

Front Genet 2021 30;12:693933. Epub 2021 Aug 30.

Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Children's Hospital, Florence, Italy.

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, = 3.03 × 10 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of , a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.
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http://dx.doi.org/10.3389/fgene.2021.693933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435735PMC
August 2021

Genetic polymorphisms involved in mitochondrial metabolism and pancreatic cancer risk.

Cancer Epidemiol Biomarkers Prev 2021 Sep 15. Epub 2021 Sep 15.

Division of Gastroenterology and Research Laboratory, Casa Sollievo della Sofferenza, IRCCS Casa Sollievo della Sofferenza.

Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC aetiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNPs) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported.

Methods: We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analysed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using MAGMA software.

Results: In the discovery phase we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P <0.05). In the second phase none of the findings were replicated. In the gene-level analysiswe observed that three genes (TERT, SUGCT and SURF1) involved in the mitochondrial metabolismshowed an association below the Bonferroni-corrected threshold of statistical significance (P=0.05/1588=3.1 x10-5).

Conclusions: Even though the mitochondrial metabolism might be involved in PDAC aetiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk.

Impact: This large case-control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0353DOI Listing
September 2021

The Role of Microbiota in Gastrointestinal Cancer and Cancer Treatment - Chance or Curse?

Cell Mol Gastroenterol Hepatol 2021 Sep 8. Epub 2021 Sep 8.

Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. Electronic address:

The gastrointestinal (GI) tract is home to a complex and dynamic community of microorganisms, comprising bacteria, archaea, viruses, yeast, and fungi. It is widely accepted that human health is shaped by these microbes and their collective microbial genome. This so-called second genome plays an important role in normal functioning of the host, contributing to processes involved in metabolism and immune modulation. Furthermore, the gut microbiota also is capable of generating energy and nutrients (eg, short-chain fatty acids and vitamins) that are otherwise inaccessible to the host and are essential for mucosal barrier homeostasis. In recent years, numerous studies have pointed toward microbial dysbiosis as a key driver in many GI conditions, including cancers. However, comprehensive mechanistic insights on how collectively gut microbes influence carcinogenesis remain limited. In addition to their role in carcinogenesis, the gut microbiota now has been shown to play a key role in influencing clinical outcomes to cancer immunotherapy, making them valuable targets in the treatment of cancer. It also is becoming apparent that, besides the gut microbiota's impact on therapeutic outcomes, cancer treatment may in turn influence GI microbiota composition. This review provides a comprehensive overview of microbial dysbiosis in GI cancers, specifically esophageal, gastric, and colorectal cancers, potential mechanisms of microbiota in carcinogenesis, and their implications in diagnostics and cancer treatment.
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http://dx.doi.org/10.1016/j.jcmgh.2021.08.013DOI Listing
September 2021

Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo-controlled multicentre trial.

United European Gastroenterol J 2021 Aug 20. Epub 2021 Aug 20.

Department of Gastroenterology, Zealand University Hospital, Køge, Denmark.

Background And Aims: Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi.

Methods: Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8.

Results: Due to insufficient patient recruitment, the trial was discontinued prematurely. The intention-to-treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health-related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double-blind phase.

Conclusions: Budesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8-weeks treatment course.
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http://dx.doi.org/10.1002/ueg2.12131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435258PMC
August 2021

Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma.

Carcinogenesis 2021 Aug;42(8):1037-1045

Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10-10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10-6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.
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http://dx.doi.org/10.1093/carcin/bgab057DOI Listing
August 2021

Evaluation of the Effectiveness of Eradication Regimens in Lithuania during the Years 2013-2020: Data from the European Registry on Management (Hp-EuReg).

Medicina (Kaunas) 2021 Jun 23;57(7). Epub 2021 Jun 23.

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

: The prevalence of in Eastern Europe remains quite high; however, there is insufficient data on the eradication regimens and their effectiveness. Therefore, the objective of the study was to evaluate the diagnostic methods and treatment of infection as well as their adherence to Maastricht V/Florence consensus during the years 2013-2020 in Lithuania. : Sub-study of the "European Registry on Management" (Hp-EuReg), international multicenter prospective non-interventional registry of the routine clinical practice. Lithuanian data from the years 2013-2020 were analyzed for effectiveness on a modified intention-to-treat (mITT) basis. 2000 adult patients, diagnosed with infection, were included. Data were compared to the European Maastricht V guidelines. : Triple-therapy was used in 90% of the cases. In 91% of the first-line prescriptions, standard triple therapy (STT) was used. The most common second-line treatment was a combination of PPI, amoxicillin and levofloxacin (PPI+A+L) (47%). The overall effectiveness in 552 cases valid for analysis was 90% by mITT. In first-line treatment, the STT effectiveness was 90% and second-line treatment with PPI+A+L achieved 92% by mITT. Increasing overall eradication rates were observed: from 72% in 2013 to more than 90% in 2018-2020, as well as a shift from 7 to 10-14 days treatments duration throughout 2013-2020. : In Lithuania, the prescribed eradication regimens for were in accordance with the international guidelines but diagnostic methods and treatment duration only partially met Maastricht V/Florence guidelines. The eradication effectiveness was improved progressively during the years 2018-2020, reaching ≥90% cure rates.
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http://dx.doi.org/10.3390/medicina57070642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305910PMC
June 2021

A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease.

N Engl J Med 2021 07;385(1):35-45

From the Institute of Translational Immunology and Celiac Center, Research Center for Immune Therapy, University Medical Center, Johannes Gutenberg University, Mainz (D.S., T.F.-S.), the Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg (J.L.), the Department of Integrative Medicine, University of Duisburg-Essen, Duisburg-Essen (J.L.), the Division of Gastroenterology, Hepatology, and Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, Tübingen (S.F.), the Department of Gastroenterology, Infectious Diseases, and Rheumatology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin (M. Schumann), the Department of Medicine II, University Hospital, Ludwig Maximilians University, Munich (H.P.T.), the Department of Medicine 1, Hector Center for Nutrition, Exercise, and Sports, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen (Y.Z.), the Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg (A.W.L.), the Department of Internal Medicine IV, University Hospital, Friedrich-Schiller University Jena, Jena (A.S.), and Dr. Falk Pharma, Freiburg (R.M., R.G.) - all in Germany; the Division of Gastroenterology and Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (D.S.); the Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital (M.M., A.P., M.-L.L.), the Faculty of Medicine and Health Technology, Tampere University (J.I., J.T.), Jilab (J.I.), and the Department of Pediatrics, Tampere University Hospital (M.-L.L.), Tampere, the Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä (J.T.), Lääkärikeskus Aava Helsinki Kamppi, Helsinki (J. Koskenpato), and Clinical Research Services Turku, Turku (M. Scheinin) - all in Finland; Oslo University Hospital, Rikshospitalet, and Stiftelsen K.G. Jebsen Celiac Disease Research Center, University of Oslo, Oslo (K.E.A.L.), the Medical Department, Innlandet Hospital Trust, Gjøvik (O.H.), and Akershus University Hospital, Lørenskog (J.J.) - all in Norway; the University of Medicine and Pharmacy "Carol Davila" and the National Institute for Mother and Child Health "Alessandrescu-Rusescu," Bucharest, Romania (A.P.); the Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania (J. Kupcinskas); the Department of Gastroenterology, Internal Medicine Clinic, Tartu University Hospital, Tartu, Estonia (K.K.); the Department of Gastroenterology and Hepatology, University Hospital Zurich (L.B., J.Z.), and the Swiss Celiac Center, Center of Gastroenterology, Clinic Hirslanden (J.Z.) - both in Zurich, Switzerland; and University College Hospital Galway, Galway, Ireland (V.B.).

Background: In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease.

Methods: In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life).

Results: Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P = 0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group.

Conclusions: In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease. (Funded by Dr. Falk Pharma; CEC-3 EudraCT number, 2017-002241-30.).
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http://dx.doi.org/10.1056/NEJMoa2032441DOI Listing
July 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

Molecular Alterations in Gastric Intestinal Metaplasia.

Int J Mol Sci 2021 May 28;22(11). Epub 2021 May 28.

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

Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC.
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http://dx.doi.org/10.3390/ijms22115758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199079PMC
May 2021

Histological disease activity in patients with microscopic colitis is not related to clinical disease activity or long-term prognosis.

Aliment Pharmacol Ther 2021 07 21;54(1):43-52. Epub 2021 May 21.

Roskilde, Denmark.

Background: Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Biopsies with characteristic histological features are crucial for establishing the diagnosis. The two main subtypes are collagenous colitis (CC) and lymphocytic colitis (LC) but incomplete forms exist. The disease course remains unpredictable varying from spontaneous remission to a relapsing course.

Aim: To identify possible histological predictors of course of disease.

Methods: Sixty patients from the European prospective MC registry (PRO-MC Collaboration) were included. Digitised histological slides stained with CD3 and Van Gieson were available for all patients. Total cell density and proportion of CD3 positive lymphocytes in lamina propria and surface epithelium were estimated by automated image analysis, and measurement of the subepithelial collagenous band was performed. Histopathological features were correlated to the number of daily stools and daily watery stools at time of endoscopy and at baseline as well as the clinical disease course (quiescent, achieved remission after treatment, relapsing or chronic active) at 1-year follow-up.

Results: Neither total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria or surface epithelium, or thickness of collagenous band showed significant correlation to the number of daily stools or daily watery stools at any point of time. None of the assessed histological parameters at initial diagnosis were able to predict clinical disease course at 1-year follow-up.

Conclusions: Our data indicate that the evaluated histological parameters were neither markers of disease activity at the time of diagnosis nor predictors of disease course.
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http://dx.doi.org/10.1111/apt.16381DOI Listing
July 2021

Recent progress in the understanding of gastric cancer - Do patients experience a benefit yet?

Best Pract Res Clin Gastroenterol 2021 Mar-Apr;50-51:101740. Epub 2021 Feb 26.

Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

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http://dx.doi.org/10.1016/j.bpg.2021.101740DOI Listing
February 2021

Molecular Characterization and Seroprevalence of Hepatitis E Virus in Inflammatory Bowel Disease Patients and Solid Organ Transplant Recipients.

Viruses 2021 04 13;13(4). Epub 2021 Apr 13.

Laboratory of Immunology, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes Str. 18, LT-47181 Kaunas, Lithuania.

Seroprevalence rates and molecular characterization of hepatitis E virus (HEV) prevalent in the Lithuanian human population has not yet been evaluated. Immunosuppressed individuals have been recognized as a risk group for chronic hepatitis due to HEV genotype 3 (HEV-3) infections. The objectives of the present study were to determine prevalence rates of anti-HEV antibodies among inflammatory bowel disease (IBD) patients and solid organ transplant (SOT) recipients, to isolate and characterize HEV strain present in the Lithuanian human population, and to investigate its capacity to infect non-human primate (MARC-145 and Vero), swine (PK-15) and murine (Neuro-2a) cells in vitro. In the present study, the significant difference of anti-HEV IgG prevalence between healthy (3.0% (95% CI 0-6.3)) and immunosuppressed individuals (12.0% [95% CI 8.1-15.9]) was described. Moreover, our findings showed that anti-HEV IgG seropositivity can be significantly predicted by increasing age (OR = 1.032, < 0.01), diagnosis of IBD (OR = 4.541, < 0.01) and reception of SOT (OR = 4.042, <0.05). Locally isolated HEV strain clustered within genotype 3i subtype of genotype 3 and was capable of infecting MARC-145 cells. This study demonstrates higher HEV seroprevalence in the risk group compared to healthy control individuals without confidence interval overlap. The high level of genetic homology between human and animal strains in Lithuania and the capacity of locally isolated strains to infect cells of non-human origin suggests its potential for zoonotic transmission.
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http://dx.doi.org/10.3390/v13040670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070591PMC
April 2021

Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.

Gut 2021 Apr 22. Epub 2021 Apr 22.

Department of Medicine I, Institute of Cancer Research, Medical University Vienna, Vienna, Austria.

Objective: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.

Design: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.

Results: We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.

Conclusion: HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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http://dx.doi.org/10.1136/gutjnl-2020-323868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292596PMC
April 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

Adverse Event Profile During the Treatment of Helicobacter pylori: A Real-World Experience of 22,000 Patients From the European Registry on H. pylori Management (Hp-EuReg).

Am J Gastroenterol 2021 06;116(6):1220-1229

Gastroenterology Unit, Athens Medical Center, Paleo Faliron General Hospital Athens, Greece.

Introduction: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management."

Methods: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control.

Results: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies.

Discussion: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.
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http://dx.doi.org/10.14309/ajg.0000000000001246DOI Listing
June 2021

Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival.

Sci Rep 2021 04 7;11(1):7570. Epub 2021 Apr 7.

Department of Biology, University of Pisa, Via Derna 1, 56126, Pisa, Italy.

Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients' response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58-15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.
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http://dx.doi.org/10.1038/s41598-021-87130-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027406PMC
April 2021

Changes in the Seroprevalence of among the Lithuanian Medical Students over the Last 25 Years and Its Relation to Dyspeptic Symptoms.

Medicina (Kaunas) 2021 Mar 9;57(3). Epub 2021 Mar 9.

Department of Gastroenterology, Lithuanian University of Health Sciences, Eiveniu str. 2, 50009 Kaunas, Lithuania.

: The prevalence of infection is decreasing in the Western world, while remaining high in developing countries. There is limited up-to-date information about the prevalence of in Central and Eastern Europe. The aim of our study was to assess the seroprevalence of and its trend over the past 25 years among students of the Lithuanian University of Health Sciences (LUHS) and to assess its relation to dyspeptic symptoms. : In the years 1995, 2012, 2016 and 2020, students from Medical and Nursing Faculties of LUHS were tested for the presence of antibodies against by performing serological tests from finger capillary blood. In addition, in the years 2012, 2016 and 2020, the students completed a gastrointestinal symptom rating scale (GSRS) questionnaire in order to assess dyspeptic symptoms. The study population consisted of 120 students in the year 1995 (mean age-21.3 ± 1.0 years), 187 students in the year 2012 (mean age-22.4 ± 0.7 years), 262 students in the year 2016 (mean age-20.4 ± 1.0 years) and 148 students in the year 2020 (mean age-20.4 ± 1.7 years). : The seroprevalence for was positive in 62 (51.7%) students in 1995, in 57 (30.4%) students in 2012, in 69 (26.3%) students in 2016 and in 21 (14.2%) students in 2020. The statistically significant difference was found between all study years, except between 2012 and 2016. There were no significant differences in frequency and intensity of upper dyspeptic symptoms between positive and negative students. : Over the last 25 years the seroprevalence of among students of LUHS has decreased significantly. No consistent differences in dyspeptic symptoms among positive and negative subgroups were found.
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http://dx.doi.org/10.3390/medicina57030254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001799PMC
March 2021

Environmental and Dietary Risk Factors for Colonic Diverticulosis and Diverticulitis.

J Gastrointestin Liver Dis 2021 Mar 13;30(1):66-72. Epub 2021 Mar 13.

Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background And Aims: Colonic diverticulosis (CD) is among the most common conditions of the large bowel. Several factors have been associated with an increased risk of CD and its complications, including advanced age, obesity, physical inactivity, and a low-fiber diet. Available data is conflicting and a comprehensive analysis of different bowel, dietary and environmental habits linked with CD is lacking. We aimed to investigate the relationship between potential risk factors and CD prevalence using full data from a colonoscopy-based cross-sectional study in Europe.

Methods: The study was conducted at three tertiary referral centers in Germany and Lithuania. It included consecutive adult patients referred for routine colonoscopy who completed a detailed questionnaire on our considered multiple risk factors for diverticulosis and diverticulitis, including dietary and environmental factors, and bowel habits.

Results: The study included 1,333 patients, 696 women and 635 men. Colonic diverticulosis was diagnosed in 858 (64%) of patients. Multivariate analysis revealed that age (OR: 1.08, 95%CI: 1.06-1.10, p<0.001) and obesity (OR: 1.05, 95%CI: 1.02-1.09, p=0.004) were associated with CD. We also revealed new risk factors for CD: increased frequency of bowel movements (OR: 0.10, 95%CI: 0.03-0.33, p<0.001) and feeling of incomplete bowel emptying (OR: 2.05, 95%CI: 1.47-2.87, p<0.001). Older participants had reduced odds (OR: 0.921, 95 CI: 0.89-0.95, p<0.05) of diverticulitis compared to younger subjects. Feeling of incomplete bowel emptying after defecation was associated with increased odds (OR: 2.769, 95% CI 1.35-5.7, p<0.006) for diverticulitis. Moreover, participants with a higher educational status had increased odds (OR: 2.453, 95%CI: 1.31-4.59, p=0.005) for diverticulitis compared to the lower education group.

Conclusions:  Study shows that older age, obesity, frequency of bowel movements, and feeling of incomplete bowel emptying are associated with the risk of CD. Furthermore, older age, feeling of incomplete bowel emptying, and higher education were associated with the risk of diverticulitis among CD patients.
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http://dx.doi.org/10.15403/jgld-3208DOI Listing
March 2021

Novel Biomarkers in the Diagnosis of Benign and Malignant GI Diseases.

Dig Dis 2021 Mar 1. Epub 2021 Mar 1.

Background: Various non-invasive biomarkers have been used in the diagnosis, prognosis and treatment of different gastrointestinal (GI) diseases for years. Novel technological developments and profound perception of molecular processes related to GI diseases over the last decade has allowed researchers to evaluate genetic, epigenetic and many other potential molecular biomarkers in different diseases and clinical settings. Here we present a review of recent most relevant papers in order to summarize major findings on novel biomarkers in the diagnosis of benign and malignant GI diseases.

Summary: Genetic variations, non-coding RNAs (ncRNAs), cell-free DNA (cfDNA), and microbiome-based biomarkers have been extensively analyzed as potential biomarkers in benign and malignant GI diseases. Multiple single nucleotide polymorphisms (SNPs) have been linked with a number of GI diseases and these observations are further being used to build-up disease specific genetic risk scores. MicroRNA and long non-coding RNAs have a large potential as non-invasive biomarkers in the management of inflammatory bowel diseases and GI tumors. Altered microbiome profiles were observed in multiple GI diseases but most of the findings still lack translational clinical application. As of today, cfDNA appears to be the most potent biomarker for early detection and screening of gastrointestinal cancers. Key messages. Novel non-invasive molecular biomarkers show huge potential as useful tools in the diagnostics and management of different GI diseases. However, the use of these biomarkers in real-life clinical practice still remains limited and further large studies are needed to elucidate the ultimate role of these potential non-invasive clinical tools.
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http://dx.doi.org/10.1159/000515522DOI Listing
March 2021

Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility.

Int J Cancer 2021 06 3;148(11):2779-2788. Epub 2021 Feb 3.

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.
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http://dx.doi.org/10.1002/ijc.33475DOI Listing
June 2021

Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study.

J Crohns Colitis 2021 Jul;15(7):1174-1183

Department of Gastroenterology, Zealand University Hospital, Køge, Denmark.

Background And Aims: The disease course of microscopic colitis [MC] is considered chronic but benign. However, this assumption is based on mainly retrospective studies, reporting on incomplete follow-up of selective cohorts. Systematic, prospective and unbiased data to inform patients and healthcare professionals on the expected course of the disease and real-life response to therapy are warranted.

Methods: A prospective, pan-European, multi-centre, web-based registry was established. Incident cases of MC were included. Data on patient characteristics, symptoms, treatment and quality of life were systematically registered at baseline and during real-time follow-up. Four disease course phenotypes were discriminated and described.

Results: Among 381 cases with complete 1-year follow-up, 49% had a chronic active or relapsing disease course, 40% achieved sustained remission after treatment and 11% had a quiescent course. In general, symptoms and quality of life improved after 3 months of follow-up. A relapsing or chronic active disease course was associated with significantly more symptoms and impaired quality of life after 1 year.

Conclusions: A minority of MC patients follow a quiescent disease course with spontaneous clinical improvement, whereas the majority suffer a chronic active or relapsing disease course during the first year after diagnosis, with persisting symptoms accompanied by a significantly impaired quality of life.
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http://dx.doi.org/10.1093/ecco-jcc/jjab007DOI Listing
July 2021

Recommendations for the diagnosis and management of transthyretin amyloidosis with gastrointestinal manifestations.

Eur J Gastroenterol Hepatol 2021 05;33(5):613-622

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Transthyretin amyloid (ATTR) amyloidosis is an adult-onset, rare systemic disorder characterized by the accumulation of misfolded fibrils in the body, including the peripheral nerves, the heart and the gastrointestinal tract. Gastrointestinal manifestations are common in hereditary (ATTRv) amyloidosis and are present even before the onset of the polyneuropathy in some cases. Delays in diagnosis of ATTRv amyloidosis with gastrointestinal manifestations commonly occur because of fragmented knowledge among gastroenterologists and general practitioners, as well as a shortage of centers of excellence and specialists dedicated to disease management. Although the disease is becoming well-recognized in the societies of Neurology and Cardiology, it is still unknown for most gastroenterologists. This review presents the recommendations for ATTRv amyloidosis with gastrointestinal manifestations elaborated by a working group of European gastroenterologists and neurologists, and aims to provide digestive health specialists with an overview of crucial aspects of ATTRv amyloidosis diagnosis to help facilitate rapid and accurate identification of the disease by focusing on disease presentation, misdiagnosis and management of gastrointestinal symptoms.
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http://dx.doi.org/10.1097/MEG.0000000000002030DOI Listing
May 2021

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

The impact of modulating the gastrointestinal microbiota in cancer patients.

Best Pract Res Clin Gastroenterol 2020 Oct - Dec;48-49:101700. Epub 2020 Oct 19.

Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania; Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania. Electronic address:

Gastrointestinal microbiota is vastly deregulated in cancer patients due to different factors, but the exact mechanisms of interaction between cancer and microbiome are still poorly understood. Current evidence suggests that alterations in the composition of the microbiota may affect efficacy and toxicity of anti-cancer therapies. Recent preclinical and clinical studies demonstrate different mechanisms and outcomes of deregulation of gut microbiome, and investigate effects of modulating gastrointestinal microbiota in cancer patients. This paper reviews effects of altered microbiome on anti-cancer management, including antibiotics, chemotherapy and immunotherapy, as well as possible outcomes of modulating altered microbiome by probiotics or faecal microbiome transplantation in cancer patients.
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http://dx.doi.org/10.1016/j.bpg.2020.101700DOI Listing
January 2021

A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.

United European Gastroenterol J 2021 03 9;9(2):229-247. Epub 2021 Mar 9.

Department of Internal Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Background: Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.

Objective: Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.

Methods: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation.

Results: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.

Conclusion: The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.
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http://dx.doi.org/10.1177/2050640620967898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259288PMC
March 2021

Endogenous motion of liver correlates to the severity of portal hypertension.

World J Gastroenterol 2020 Oct;26(38):5836-5848

Institute for Digestive Research and Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania.

Background: Degree of portal hypertension (PH) is the most important prognostic factor for the decompensation of liver cirrhosis and death, therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH (CSPH) and severe PH (SPH). As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient (HVPG), the search for non-invasive methods to diagnose these conditions is actively ongoing.

Aim: To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.

Methods: Of 36 patients with liver cirrhosis and measured HVPG were included in the case-control study. Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal ( , , ) and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm. Average endogenous strain and standard deviation of strain were assessed in the regions of interest (ROI) (1 cm × 1 cm and 2 cm × 2 cm in size) and different frequency subbands of endogenous motion (0-10 Hz and 10-20 Hz).

Results: Four parameters showed statistically significant ( < 0.05) correlation with HVPG measurement. The strongest correlation was obtained for the standard deviation of strain (estimated at 0-10 Hz and 2 cm × 2 cm ROI size). Three parameters showed statistically significant differences between patient groups with CSPH, but only showed significant results in SPH analysis. According to ROC analysis area under the curve (AUC) of the parameter reached 0.71 ( = 0.036) for the diagnosis of CSPH; with a cut-off value of 1.28 μm/cm providing 73% sensitivity and 70% specificity. AUC for the diagnosis of CSPH for was 0.78 ( = 0.0024); with a cut-off value of 3.92 μm/cm providing 73% sensitivity and 80% specificity. parameter had an AUC of 0.86 ( = 0.0001) for the diagnosis of CSPH and 0.84 ( = 0.0001) for the diagnosis of SPH. A cut-off value of -132.34 μm yielded 100% sensitivity for both conditions, whereas specificity was 80% and 72% for CSPH and SPH respectively.

Conclusion: The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.
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http://dx.doi.org/10.3748/wjg.v26.i38.5836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579755PMC
October 2020

Fusobacterium nucleatum is associated with worse prognosis in Lauren's diffuse type gastric cancer patients.

Sci Rep 2020 10 1;10(1):16240. Epub 2020 Oct 1.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.

Fusobacterium nucleatum (F. nucleatum) is frequently detected in primary colorectal cancer (CRC) and matching metastasis, and has been linked to a worse prognosis. We investigated the presence of F. nucleatum in gastric cancer (GC) and gastric preneoplastic conditions of the stomach, and its potential prognostic value in GC patients. Fusobacterium spp. and F. nucleatum were quantified in various specimens from gastrointestinal tract including paired CRC and GC tissues using probe-based qPCR. Fusobacterium spp. and F. nucleatum were more frequently found in tumorous tissue of CRC and GC compared to non-tumorous tissues. The frequency and bacterial load were higher in CRC compared to GC patients. F. nucleatum positivity showed no association to chronic gastritis or preneoplastic conditions such as intestinal metaplasia. F. nucleatum-positivity was associated with significantly worse overall survival in patients with Lauren's diffuse type, but not with intestinal type GC. There was no association with gender, Helicobacter pylori-status, tumor stage or tumor localization. However, F. nucleatum was positively associated with patient's age and a trend for a lower global long interspersed element-1 DNA methylation. In conclusion, our work provides novel evidence for clinical relevance of F. nucleatum in GC by showing an association between F. nucleatum positivity with worse prognosis of patients with Laurens's diffuse type gastric cancer. Further studies are necessary to explore related mechanistic insights and potential therapeutic benefit of targeted antibiotic treatment in GC patients.
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http://dx.doi.org/10.1038/s41598-020-73448-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530997PMC
October 2020

Biopsy Sampling in Upper Gastrointestinal Endoscopy: A Survey from 10 Tertiary Referral Centres Across Europe.

Dig Dis 2021 1;39(3):179-189. Epub 2020 Oct 1.

Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background: Guidelines give robust recommendations on which biopsies should be taken when there is endoscopic suggestion of gastric inflammation. Adherence to these guidelines often seems arbitrary. This study aimed to give an overview on current practice in tertiary referral centres across Europe.

Methods: Data were collected at 10 tertiary referral centres. Demographic data, the indication for each procedure, endoscopic findings, and the number and sampling site of biopsies were recorded. Findings were compared between centres, and factors influencing the decision to take biopsies were explored.

Results: Biopsies were taken in 56.6% of 9,425 procedures, with significant variation between centres (p < 0.001). Gastric biopsies were taken in 43.8% of all procedures. Sampling location varied with the procedure indication (p < 0.001) without consistent pattern across the centres. Fewer biopsies were taken in centres which routinely applied the updated Sydney classification for gastritis assessment (46.0%), compared to centres where this was done only upon request (75.3%, p < 0.001). This was the same for centres stratifying patients according to the OLGA system (51.8 vs. 73.0%, p < 0.001). More biopsies were taken in centres following the MAPS guidelines on stomach surveillance (68.1 vs. 37.1%, p < 0.001). Biopsy sampling was more likely in younger patients in 8 centres (p < 0.05), but this was not true for the whole cohort (p = 0.537). The percentage of procedures with biopsies correlated directly with additional costs charged in case of biopsies (r = 0.709, p = 0.022).

Conclusion: Adherence to guideline recommendations for biopsy sampling at gastroscopy was inconsistent across the participating centres. Our data suggest that centre-specific policies are applied instead.
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http://dx.doi.org/10.1159/000511867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220928PMC
May 2021
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