Publications by authors named "George Karamanolis"

58 Publications

Specific Neuropeptide Expression in Crohn's Disease Ileocolonic Resection Specimens Is Not Associated with Plexitis at the Ileal Margin or Postoperative Recurrence.

J Gastrointest Surg 2022 Jan 8. Epub 2022 Jan 8.

Second Department of Surgery, Aretaieion University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background: Myenteric plexitis is considered a risk factor for postoperative recurrence (POR) in Crohn's disease (CD). The primary purpose of this study was to evaluate the association between neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and substance P (SP) expression and plexitis at the proximal resection margin. The secondary aim was to identify risk factors for POR.

Methods: A retrospective, single-center study on CD patients who underwent ileocolonic resection (ICR) between January 2010 and December 2016 was conducted. The presence and severity of plexitis were evaluated by hematoxylin and eosin stain. Mast cells were highlighted by Giemsa stain. Immunohistochemistry was used to identify T lymphocytes and NPY-, VIP-, and SP-ergic neurons. Neuropeptide expression was quantified using image analysis.

Results: Seventy-nine patients were included. No association was detected between NPY, VIP, and SP expression and plexitis. Similarly, the number of involved inflammatory cells, T lymphocytes or mast cells was not correlated with neuropeptide expression. Smoking (hazard ratio [HR] 4.07; 95% confidence interval [CI] 2.08-7.94; p < 0.001), moderate (HR 3.68; 95%CI 1.06-12.73; p = 0.040), and severe myenteric plexitis (HR 7.36; 95%CI 1.12-48.30; p = 0.037) were independent risk factors for endoscopic POR, whereas smoking (HR 2.78; 95%CI 1.01-7.67; p = 0.049), severe myenteric plexitis (HR 20.03; 95%CI 1.09-368.28; p = 0.044), and involved ileal margin (HR 3.45; 95%CI 1.33-8.96; p = 0.011) for clinical POR.

Conclusions: Smoking, moderate or severe myenteric plexitis, and involved ileal margin negatively affect POR in CD patients undergoing ICR. Submucosal and myenteric plexitis at the proximal resection margin is not related to the expression of specific neuropeptides.
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http://dx.doi.org/10.1007/s11605-021-05215-7DOI Listing
January 2022

Graded pneumatic dilation in subtype I and II achalasia: long-term experience in a single center.

Ann Gastroenterol 2022 Jan-Feb;35(1):28-33. Epub 2021 Dec 9.

Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy (Francesco Torresan, Fabio Cortellini, Francesco Azzaroli, Daniele Mandolesi, Franco Bazzoli).

Background: The efficacy of pneumatic dilation (PD) in the management of achalasia has yielded variable results. The availability of high-resolution manometry led to the identification of 3 clinically relevant subtypes of achalasia, revealing the poor efficacy of PD in subtype III. Furthermore, PD showed a lower response rate in patients with subtype III compared to laparoscopic Heller myotomy and peroral endoscopic myotomy. This study aimed to investigate the short- and long-term efficacy, safety profile and side effects of PD with a "graded approach" in subtypes I and II achalasia.

Methods: We enrolled 141 patients (male 67, mean age=66±16.26 years) with achalasia (n=27 subtype I, n=74 subtype II and n=40 subtype III) between January 2010 and July 2020 at St. Orsola University Hospital, Bologna, Italy. We analyzed the data of patients with subtypes I and II, who underwent a graded-protocol PD. Short- and long-term clinical efficacy, complications and gastroesophageal reflux disease (GERD) were recorded.

Results: One month after graded protocol PD, 100% subtype I and 96.2% subtype II achalasia patients showed clinical remission. The PD procedure was completed without major complications in all patients. In the long-term follow up (median time: 56 months), 95.5% subtype I and 90% subtype II achalasia patients had an Eckardt score ≤3. GERD occurred in 27.7% of all patients.

Conclusion: A graded-protocol PD applied in the appropriate achalasia subtypes was shown to be a safe and highly effective approach, in both the short- and long-term.
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http://dx.doi.org/10.20524/aog.2021.0683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713348PMC
December 2021

Safety of Immunizations for the Adult Patient With Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.

Inflamm Bowel Dis 2021 Nov 24. Epub 2021 Nov 24.

Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA.

Background: Patients with inflammatory bowel disease (IBD) have low vaccination rates for vaccine-preventable diseases. Fear of adverse reactions (AEs) appear to negatively affect vaccination efforts. We aimed to systemically review the risks for AEs following immunization for patients with IBD.

Methods: We searched PubMed and Embase until April 15, 2020, for studies evaluating the safety of vaccinations among patients with IBD. The primary outcome was the incidence of systemic and local AEs among vaccinated patients. Secondary outcome was the rate of IBD flare following immunization. We utilized a random effects meta-analysis of proportions using the DerSimonian-Laird approach to estimate the safety of immunizations.

Results: A total of 13 studies with 2116 patients was included in our analysis after fulfilling our inclusion criteria. Seven studies examined the influenza vaccine, 4 the pneumococcal vaccine, 1 the recombinant zoster vaccine, and 1 the hepatitis B vaccine. Follow-up of patients was up to 6 months. The majority of AEs were local, with a pooled incidence of 24% (95% CI, 9%-42%) for all vaccines. Systemic AEs were mostly mild, without resulting in hospitalizations or deaths, with a pooled incidence of 16% (95% CI, 6%-29%) for all vaccines. Flare of inflammatory bowel disease after vaccination found with a pooled incidence of 2% (95% CI, 1%-4%) and we include in the analysis data from all immunizations examined.

Discussion: Our study demonstrated that AEs after vaccination are mainly local or mildly systemic and do not differ significantly from the expected AE after recommended immunizations for the general population. Thus, gastroenterologists should reinforce that vaccines are safe in patients with IBD.
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http://dx.doi.org/10.1093/ibd/izab266DOI Listing
November 2021

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

Neurogastroenterol Motil 2021 09;33(9):e14238

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1111/nmo.14238DOI Listing
September 2021

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

J Cell Mol Med 2021 08 24;25(16):8047-8061. Epub 2021 Jun 24.

Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
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http://dx.doi.org/10.1111/jcmm.16736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358858PMC
August 2021

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

United European Gastroenterol J 2021 04;9(3):307-331

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1002/ueg2.12061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259261PMC
April 2021

Leucine-rich alpha-2 glycoprotein 1, high mobility group box 1, matrix metalloproteinase 3 and annexin A1 as biomarkers of ulcerative colitis endoscopic and histological activity.

Eur J Gastroenterol Hepatol 2020 09;32(9):1106-1115

Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens.

Objective: The LRG, HMGB1, MMP3 and ANXA1 proteins have been implicated in different inflammatory pathways in ulcerative colitis (UC), but their role as specific biomarkers of both endoscopic and histological activity has yet to be elucidated. In the present study, we aimed to evaluate the LRG1, HMGB1, MMP3 and ANXA1 as potential serum biomarkers for UC endoscopic and histological activity.

Methods: This cross-sectional study included UC patients under 5-ASA, and healthy controls (HC) undergoing colonoscopy. Blood and biopsy samples were obtained and endoscopic Mayo sub-score (Ms) was recorded for the UC patients. Intramucosal calprotectin as a marker of histologic activity was evaluated in all biopsy samples and serum LRG1, HMGB1, MMP3 and ANXA1 levels were measured in the blood samples.

Results: The HCs ANXA1 level was lower compared to that of the UC group [P = 0.00, area under the curve (AUC) = 0.881] and so was the HCs MMP3 level compared to that of patients (P = 0.00, AUC = 0.835). The HCs ANXA1 levels were also lower compared to these of the independent Ms groups, even to the Ms = 0 (P = 0.00, AUC = 0.913). UC endoscopic activity was associated with MMP3 levels (r = 0.54, P = 0.000) but not with ANXA1, LRG1 and HMGB1 levels CONCLUSION: Serum ANXA1 is a potential diagnostic biomarker of UC and serum MMP3 is a potential biomarker of UC endoscopic and histological activity.
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http://dx.doi.org/10.1097/MEG.0000000000001783DOI Listing
September 2020

International consensus on the diagnosis and management of dumping syndrome.

Nat Rev Endocrinol 2020 08 26;16(8):448-466. Epub 2020 May 26.

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Catholic University of Leuven, Leuven, Belgium.

Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.
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http://dx.doi.org/10.1038/s41574-020-0357-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351708PMC
August 2020

Ghrelin Gene Polymorphisms in Irritable Bowel Syndrome.

Digestion 2021 15;102(3):313-318. Epub 2020 Apr 15.

Department of Basic Medical Science, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece,

Introduction/objective: Irritable bowel syndrome (IBS) is a bowel disorder characterized by pain accompanying defecation or altered bowel habits, divided into diarrhea-predominant, constipation-predominant, and alternating subtypes, whose pathogenesis is considered to include disordered bowel motility. The hormone ghrelin is a growth hormone secretagogue which furthermore affects gastrointestinal motility. We study the association between its genetic polymorphisms and the risk for IBS.

Methods: IBS patients meeting the Rome III criteria and controls similar in age and gender were recruited. Whole blood samples were used for genotyping via polymerase chain reaction and restriction fragment length polymorphism for the polymorphisms rs34911341, rs696217, and rs2075356.

Results: Participants included 142 patients and 209 controls. The rs696217 GG genotype frequency was higher in patients (78.87%) compared to controls (55.5%). The rs696217 GT genotype was significantly less frequent among patients than in controls (OR 0.31, 95% CI 0.19-0.52), as was the T allele (OR 0.43, 95% CI 0.28-0.66). No significant differences in genotype distribution were found for the rs34911341 and rs2075356 polymorphisms between patients and controls. The genotype frequencies did not significantly differ between IBS subtype groups for any of the polymorphisms studied.

Conclusions: The GG and GT genotypes of the rs696217 polymorphism, as well as the G-allele, demonstrate significant association with IBS susceptibility, while the T allele appears to bear a protective effect. Ghrelin's polymorphisms are plausibly involved in IBS pathogenesis, but do not correlate with any distinct IBS subtype.
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http://dx.doi.org/10.1159/000506306DOI Listing
August 2021

High prevalence of asymptomatic peptic ulcers diagnosed during screening endoscopy in patients with cirrhosis.

Ann Gastroenterol 2019 Sep-Oct;32(5):451-456. Epub 2019 Jul 6.

Academic Department of Gastroenterology and Hepatology, LAIKO General Hospital, University of Athens, Medical School, Athens, Greece.

Background: Peptic ulcer disease (PUD) is more prevalent in cirrhotics and this may aggravate prognosis. We investigated the prevalence of PUD in cirrhotics and its potential association with () infection, the underlying etiology and severity of liver disease, and other manifestations of portal hypertension (PH).

Methods: We enrolled consecutive asymptomatic cirrhotic patients who underwent screening endoscopy in a tertiary hospital during a 12-month period. We recorded the presence of PUD and the endoscopic findings associated with PH. infection was documented through either histology or CLO-test. The diagnosis of cirrhosis was based on elastography, liver biopsy or a combination of clinical, biochemical and imaging data.

Results: One hundred patients (M/F: 54/46, mean age: 61±14 years) were included in the analysis. Viral hepatitis (37%) and alcohol (22%) were the most common causes of cirrhosis. Child-Pugh stage was A/B/C: 60/35/5. PUD was found in 19 patients (14 gastric, 5 duodenal). infection was diagnosed in 54%. Varices were detected in 59% (39% needed treatment). PH gastropathy was present in 81% (severe in 33%). The presence of PUD was unrelated to the etiology and the severity of liver disease or to other endoscopic manifestations of PH. No correlation was found between PUD and infection.

Conclusions: A high prevalence of PUD was observed in our cirrhotic patients, although they were asymptomatic and had no known risk factors of ulcerogenicity. The value of screening endoscopy for the early diagnosis and treatment of PUD in cirrhotics deserves further investigation.
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http://dx.doi.org/10.20524/aog.2019.0399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686096PMC
July 2019

Polymorphisms of the BARX1 and ADAMTS17 Locus Genes in Individuals With Gastroesophageal Reflux Disease.

J Neurogastroenterol Motil 2019 Jul;25(3):436-441

Gastroenterology Unit, 2nd Department of Surgery, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background/aims: Gastroesophageal reflux disease (GERD) represents a common condition having a substantial impact on the patients' quality of life, as well as the health system. According to many studies, the and genes have been suggested as genetic risk loci for the development of GERD and its complications. The purpose of this study is to investigate the potential association between GERD and and polymorphisms.

Methods: The present is a prospective cohort study of 160 GERD patients and 180 healthy control subjects of Greek origin, examined for BARX1 and ADAMTS17 polymorphisms (rs11789015 and rs4965272) and a potential correlation to GERD.

Results: The rs11789015 AG and GG genotypes were found to be significantly associated with GERD (= 0.032; OR, 1.65; 95% CI, 1.062.57 and = 0.033; OR, 3.00; 95% CI, 1.15-7.82, respectively), as well as the G allele (= 0.007; OR, 1.60; 95% CI, 1.14- 2.24). Concerning the rs4965272, only the GG genotype was significantly associated with GERD (= 0.035; OR, 3.42; 95% CI, 1.06-11.05).

Conclusions: This is a study investigating the potential correlation between and polymorphisms and the development of GERD, showing a considerable association between both polymorphisms and the disease. This finding suggests that esophageal differentiation or altered regulation on microfibrils in the cell environment could be implicated as possible mechanisms in the pathogenesis of GERD.
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http://dx.doi.org/10.5056/jnm18183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657930PMC
July 2019

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

Endoscopy 2019 05 3;51(5):472-491. Epub 2019 Apr 3.

Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.
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http://dx.doi.org/10.1055/a-0862-0346DOI Listing
May 2019

Risk factors for gastroesophageal reflux disease and analysis of genetic contributors.

World J Clin Cases 2018 Aug;6(8):176-182

Gastroenterology Unit, 2 Department of Surgery, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including: (1) motor abnormalities, such as impaired lower esophageal sphincter (LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and (2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD- related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like , , , anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett's esophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis, specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.
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http://dx.doi.org/10.12998/wjcc.v6.i8.176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107529PMC
August 2018

Correlation of polymorphisms in long non-coding RNAs with the pathogenesis of inflammatory bowel diseases.

Dig Liver Dis 2018 Jun 13;50(6):624-626. Epub 2018 Mar 13.

Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2018.03.008DOI Listing
June 2018

Evaluation and management of esophageal manifestations in systemic sclerosis.

Ann Gastroenterol 2018 Mar-Apr;31(2):165-170. Epub 2018 Jan 18.

Academic Department of Gastroenterology, National and Kapodistrian University of Athens, "Laikon" General Hospital, Athens, Greece.

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.
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http://dx.doi.org/10.20524/aog.2018.0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825946PMC
January 2018

Association of miR-146 rs2910164, miR-196a rs11614913, miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn's disease.

World J Gastrointest Pharmacol Ther 2017 Nov;8(4):193-200

Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Aim: To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease (CD).

Methods: One hundred seven patients with CD based on standard clinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the Harvey-Bradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Whole peripheral blood was extracted and genotyping was performed by PCR.

Results: One hundred and seven patients were included in the study. Seventy two (67.3%) patients were classified as complete responders, 22 (20.5%) as partial while 13 (12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to anti-TNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.

Conclusion: No correlation is detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.
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http://dx.doi.org/10.4292/wjgpt.v8.i4.193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680166PMC
November 2017

Long non-coding RNA in pancreatic adenocarcinoma and pancreatic neuroendocrine tumors.

Ann Gastroenterol 2017 4;30(6):622-628. Epub 2017 Aug 4.

Gastroenterology Unit, 2 Department of Surgery, Aretaieio University Hospital, National and Kapodistrian University of Athens (George Karamanolis), Greece.

Interest in non-coding regions of DNA has been increasing since the mapping of the human genome revealed that human DNA contains far fewer genes encoding proteins than previously expected. However, analysis of the derivatives of DNA transcription (transcriptomics) revealed that the majority of the genetic material is transcribed into non-coding RNA (ncRNA), indicating that these molecules probably provide the functional diversity and complexity of the physiology of the human body that cannot be attributed to the proteins. Of these ncRNA, long ncRNA (lncRNA) have a length greater than 200 nucleotides and share many common components with the coding messenger RNA (mRNA): They are transcribed by RNA polymerase II, comprised of multiple exons and subjected to normal RNA splicing giving RNA products of several kilobases. Scientific data reveal the regulatory role of lncRNA in the control of gene expression during cell development and homeostasis. However, to date, very few lncRNAs have been characterized in depth, and lncRNAs are thought to have a wide range of functions in cellular and developmental processes. These molecules will have the possibility to be used as biomarkers and contribute to the development of targeted therapies. Concerning pancreatic cancer, there are limited data in the literature that correlate the growth of these tumors with deregulation of various lncRNA. We herein review the literature regarding the role of lncRNA as a diagnostic and prognostic biomarker and possible therapeutic target in the neoplasms of the pancreas, particularly pancreatic adenocarcinoma and pancreatic neuroendocrine tumors.
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http://dx.doi.org/10.20524/aog.2017.0185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670281PMC
August 2017

The contribution of long non-coding RNAs in Inflammatory Bowel Diseases.

Dig Liver Dis 2017 Oct 9;49(10):1067-1072. Epub 2017 Aug 9.

Academic Department of Gastroenterology, Laiko General Hospital, Medical School, Athens University, Athens, Greece.

Inflammatory bowel diseases (IBDs) are multifactorial autoimmune diseases with growing prevalence but the interaction between genetic, environmental and immunologic factors in their development is complex and remains obscure. There is great need to understand their pathogenetic mechanisms and evolve diagnostic and therapeutic tools. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are known to interfere in gene regulation but their roles and functions have not yet been fully understood. While they are widely investigated in cancers, little is known about their contribution in other diseases. There is growing evidence that lncRNAs play critical role in regulation of immune system and that they interfere in the pathogenetic mechanisms of autoimmune diseases, like IBDs. Recent studies have identified lncRNAs in the proximity of IBD-associated genes and single nucleotide polymorphisms within IBD-associated lncRNAs as well. Furthermore, blood samples and pinch biopsies were also analyzed and a plethora of lncRNAs are found to be deregulated in Crohn's disease (CD), Ulcerative colitis (UC) or both. (Especially in UC samples the lncRNAs INFG-AS1 and BC012900 were found to be significantly up-regulated. Similarly, ANRIL, a lncRNA that nest different disease associated SNPs, is significantly down-regulated in inflamed IBD tissue.) This review aims at recording for the first time recent data about lncRNAs found to be deregulated in IBDs and discussing suggestive pathogenetic mechanisms and future use of lncRNAs as biomarkers.
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http://dx.doi.org/10.1016/j.dld.2017.08.003DOI Listing
October 2017

Identification of serum proteome signature of irritable bowel syndrome: Potential utility of the tool for early diagnosis and patient's stratification.

J Proteomics 2018 09 28;188:167-172. Epub 2017 Jul 28.

Department of Basic Medical Sciences, Laboratory of Biology Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with high incidence, and great heterogeneity of symptoms. Numerous factors are correlated with IBS development; however, the pathophysiology is not yet clear. In addition, there is no appropriate diagnostic tool available. The aim of this study was the identification of protein expression alterations in IBS patients compared to healthy individuals. Serum samples from 30 IBS patients (10 with IBS-Diarrhea, 10 IBS-Constipation and 10 IBS-Mixed) and 10 healthy individuals were subjected to proteomic analysis by 2-dimensional gel electrophoresis. Following evaluation of densitometrical data, protein spots exhibiting differential expression among the groups, were further characterized by matrix-assisted laser desorption tandem time-of-flight mass spectrometer and the results were confirmed by Western blot analysis. Eight significantly different expressed proteins were identified. Seven of them were overexpressed in IBS cases and only one was overexpressed in healthy individuals. These proteins were also differently expressed between the three IBS subgroups. IBS-D group overexpressed immunoglobulin light chain Lambda (LAC3) and apolipoprotein E (APOE), IBS-C group overexpressed apolipoprotein H (APOH) and collagen alpha-1 (XIV) chain (COEA1), and IBS-M group and healthy individuals overexpressed retinol-binding protein 4 (RET4). Our results show a different serum protein profile of IBS patients compared to healthy controls. Understanding the role of these eight proteins which are differently expressed in IBS patients, may contribute to a better clarification of IBS pathogenesis and to patient's stratification.

Significance: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with high incidence and great heterogeneity of symptoms without any appropriate diagnostic tool available. Eight significantly different expressed proteins were identified. Seven of them were overexpressed in IBS cases and only one was expressed in healthy individuals. These proteins were also differently expressed between the three IBS subgroups. Our results show that there is a different serum proteome signature in IBS compared to healthy individuals, as well as in IBS subgroups that could be used in the future for patient's stratification and as a diagnostic tool.
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http://dx.doi.org/10.1016/j.jprot.2017.07.019DOI Listing
September 2018

Proton pump inhibitor and selective serotonin reuptake inhibitor therapy for the management of noncardiac chest pain.

Eur J Gastroenterol Hepatol 2017 Sep;29(9):1054-1058

aDepartment of Gastroenterology, Evangelismos Hospital bAcademic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.

Introduction: Although gastroesophageal reflux disease is the main cause of noncardiac chest pain (NCCP), proton pump inhibitors (PPIs) benefit a minority of patients. Our prospective study evaluated the effect of PPI and selective serotonin reuptake inhibitors on the different subtypes of NCCP characterized by impedance-pH monitoring.

Methods: All NCCP patients underwent impedance-pH monitoring and on the basis of the results, those with abnormal distal esophageal acid exposure received PPIs twice daily (group A), those with a positive symptom index for chest pain received citalopram 20 mg and PPI once daily (group B), and those with a negative symptom index for chest pain received citalopram 20 mg once daily (group C). Therapy was administered for 12 weeks and treatment success was defined as complete disappearance of chest pain.

Results: From March 2015 to March 2016, 63 patients were included (group A=9, group B=18, group C=36). After 12 weeks of therapy, complete resolution of chest pain was noted in 8/9 (88.9%) group A, 13/18 (72.2%) group B, and 24/36 (66.7%) group C patients.

Conclusion: Combined impedance-pH monitoring identifies different subtypes of NCCP patients who can receive tailored management. Targeted therapy with PPIs and/or citalopram offers complete symptom relief in the great majority of them.
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http://dx.doi.org/10.1097/MEG.0000000000000925DOI Listing
September 2017

Proteomics and irritable bowel syndrome.

Expert Rev Proteomics 2017 05 17;14(5):461-468. Epub 2017 Apr 17.

c Department of Basic Medical Sciences, Laboratory of Biology Medical School , National and Kapodistrian University of Athens , Athens , Greece.

Introduction: Irritable bowel syndrome (IBS) is a gastrointestinal disease that according to Rome IV criteria is subdivided into four subtypes. The pathophysiology of this disease is not well understood due to numerous factors playing multiple roles in disease development, such as diet, stress and hormones. IBS has a variety of symptoms and overlaps with many other gastrointestinal and non-gastrointestinal diseases. Area covered: This review aims to present an overview of implementation of proteomics in experimental studies in the field of IBS. Expert commentary: Proteomics is commonly used for biomarker discovery in and has also been extensively used in IBS research. The necessity of a sensitive and specific biomarker for IBS is apparent, but despite the intensive research performed in this field, an appropriate biomarker is not yet available.
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http://dx.doi.org/10.1080/14789450.2017.1317600DOI Listing
May 2017

Intestinal Bacteria Composition and Translocation of Bacteria in Inflammatory Bowel Disease.

PLoS One 2017 18;12(1):e0170034. Epub 2017 Jan 18.

Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Background: Live commensal intestinal bacteria are present in the peripheral blood where they can induce inflammation.

Objective: To evaluate the intestinal bacteria composition and translocation of bacteria in IBD.

Methods: Both blood and tissue biopsy samples were collected from adult patients with active/inactive Crohn's disease (CD), active/inactive ulcerative colitis (UC) and healthy individuals. Most of the patients were newly diagnosed and none of them received antibiotics. Using a reverse transcription-quantitative real-time PCR (RT-qPCR) method, we determined the composition of microbiota. NOD2/CARD15 genotyping was also studied.

Results: Total bacterial DNA concentration was increased in tissue and blood samples of IBD patients compared to healthy controls. Furthermore, the active IBD cases had higher total bacterial DNA concentration levels compared to the inactive cases. Three species characterized dysbiosis in IBD, namely an increase of Bacteroides spp in active and inactive IBD samples, and a decrease in Clostridium leptum group (IV), and Faecalibacterium prausnitzi in both active and inactive IBD patients. No significant association between bacterial translocation and NOD2/CARD15 mutations was found.

Conclusions: The composition of the microbiota in IBD patients differs from that of healthy controls. The high rate of bacterial DNA in the blood samples indicates translocation in inflammatory bowel disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170034PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242456PMC
August 2017

Adherence to follow-up and treatment recommendations in Greek and immigrant patients with chronic hepatitis B in Greece.

Eur J Gastroenterol Hepatol 2017 Mar;29(3):264-270

Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.

Background/aim: Immigrants have multiple barriers to access to health care systems. We evaluated the adherence to follow-up and treatment recommendations of chronic hepatitis B virus (HBV) Greek and immigrant patients.

Methods: In total, 1001 consecutive adult patients with chronic HBV infection who visited our clinics for the first time between 2002 and 2011 were included. All patients born outside Greece were considered immigrants. Diagnosis was considered to be complete if patients could be classified into HBeAg-positive chronic hepatitis B (CHB), inactive carriers, HBeAg-negative CHB, or decompensated cirrhosis.

Results: Of the patients, 56% were Greeks and 44% were immigrants. Greeks visited our clinics at a significantly older mean age (50 vs. 35 years, P<0.001) and more frequently with advanced liver disease (11.4 vs. 6.4%, P=0.007). During the first year, Greeks more frequently had several tests and eventually a complete diagnosis (68 vs. 55%, P<0.001). Greeks were more frequently in the phase of HBeAg-negative CHB and less frequently in the phase of inactive carrier or HBeAg-positive CHB, but age was the main determinant for these differences in multivariate analysis. Treatment was initiated more frequently by Greeks than immigrants with treatment indications (86 vs. 65%, P<0.001). Only 30-33% of treated and 4-10% of untreated patients remained under follow-up at year 5, without significant differences between Greeks and immigrants.

Conclusion: Adherence to follow-up recommendations is rather poor for all chronic HBV patients. Immigrants are lost more frequently during the first year, but only small proportions of treated and particularly untreated Greek or immigrant patients remain under long-term follow-up.
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http://dx.doi.org/10.1097/MEG.0000000000000788DOI Listing
March 2017

The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial.

Arthritis Res Ther 2016 09 1;18:195. Epub 2016 Sep 1.

Joint Academic Rheumatology Programme, Athens Medical School National and Kapodistrian University, Athens, Greece.

Background: Acute administration of the oral 5-HT1A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc).

Methods: Thirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged.

Results: Eight patients did not complete the trial because of buspirone-associated dizziness (n = 2), or nausea (n = 2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7 ± 3.9 to 12.2 ± 4.6 mmHg (p = 0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r = -0.589, p = 0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p = 0.001, and p = 0.022, respectively).

Conclusion: Our findings warrant more conclusive evaluation with a double-blind controlled study; however, buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment.

Trial Registration: ClinicalTrials.gov Identifier: NCT02363478 Registered: 21-02-2014.
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http://dx.doi.org/10.1186/s13075-016-1094-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009650PMC
September 2016

Specific detection of OCT4 isoforms in inflammatory bowel disease.

Gut Pathog 2015 1;7:25. Epub 2015 Oct 1.

Laboratory of Biology, Department of Basic Medical Sciences, School of Medicine, University of Athens, Michalakopoulou 176, 11527 Athens, Greece.

Background: Developmentally early cells are mobilized into peripheral blood in Crohn's disease (CD) patients. OCT4, is considered to be important in sustaining the pluripotency of stem cells. OCT4 splicing variants are differentially expressed in pluripotent and non-pluripotent cells. Our study aims to investigate the expression pattern of OCT4 variants and SOX-2, an essential factor implicated in self-renewal and pluripotency, in tissue and blood samples from patients with IBD.

Methods: Peripheral blood and tissue samples were collected from patients with active CD and ulcerative colitis (UC), and from healthy individuals. OCT4 expression was documented by Western blot, immunohistochemistry and by reverse transcription-real-time PCR. OCT4 isoform determination was documented using specific primers. SOX-2 expression levels were also evaluated.

Results: OCT4 protein levels were significantly higher in CD tissue samples than in CD blood samples, and in UC tissue samples. OCT4 protein was localized mainly in the cytosol. In all samples, only the OCT4 pseudogenes and the OCT4B1 variant were detected. OCT4B1 expression levels were elevated in both tissue and blood samples from CD and UC cases compared to healthy controls. In CD patients only SOX-2 mRNA levels were found slightly increased compared to healthy controls.

Conclusion: Our results suggest that OCT4 is expressed in patients with IBD. Furthermore, we found the presence of the OCT4B1 isoform in IBD in both tissue and blood samples. Our results have shown, that developmentally early cells might be mobilized into peripheral blood as result of tissue damage, indicating a possible role of these cells in repair of injured intestinal tract.
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http://dx.doi.org/10.1186/s13099-015-0073-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591585PMC
October 2015

Gene polymorphisms associated with functional dyspepsia.

World J Gastroenterol 2015 Jul;21(25):7672-82

Anastasia Kourikou, George D Dimitriadis, Konstantinos Triantafyllou, Hepatogastroenterology Unit, Second Department of Internal Medicine and Research Institute, Attikon University General Hospital, Medical School, Athens University, 12462 Haidari, Greece.

Functional dyspepsia (FD) is a constellation of functional upper abdominal complaints with poorly elucidated pathophysiology. However, there is increasing evidence that susceptibility to FD is influenced by hereditary factors. Genetic association studies in FD have examined genotypes related to gastrointestinal motility or sensation, as well as those related to inflammation or immune response. G-protein b3 subunit gene polymorphisms were first reported as being associated with FD. Thereafter, several gene polymorphisms including serotonin transporter promoter, interlukin-17F, migration inhibitory factor, cholecystocynine-1 intron 1, cyclooxygenase-1, catechol-o-methyltransferase, transient receptor potential vanilloid 1 receptor, regulated upon activation normal T cell expressed and secreted, p22PHOX, Toll like receptor 2, SCN10A, CD14 and adrenoreceptors have been investigated in relation to FD; however, the results are contradictory. Several limitations underscore the value of current studies. Among others, inconsistencies in the definitions of FD and controls, subject composition differences regarding FD subtypes, inadequate samples, geographical and ethnical differences, as well as unadjusted environmental factors. Further well-designed studies are necessary to determine how targeted genes polymorphisms, influence the clinical manifestations and potentially the therapeutic response in FD.
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http://dx.doi.org/10.3748/wjg.v21.i25.7672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491956PMC
July 2015

Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study.

United European Gastroenterol J 2015 Jun;3(3):266-71

Academic Department of Gastroenterology, Athens Medical School, "Laiko" GH, Athens, Greece.

Background: Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers.

Aim: We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc.

Methods: Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined.

Results: Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 ± 2.6 to 11.53 ± 3.4 mmHg (p = 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p = 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure ( + 2.11 ± 2.0 versus -0.45 ± 2.3 mmHg, p = 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function.

Conclusion: The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted.
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http://dx.doi.org/10.1177/2050640614560453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480533PMC
June 2015

Association of survivin promoter polymorphisms with inflammatory bowel disease and response to antitumor necrosis factor therapy.

Genet Test Mol Biomarkers 2015 Jun 28;19(6):339-43. Epub 2015 Apr 28.

2 Second Department of Surgery, Aretaieion Hospital, Medical School, University of Athens , Athens, Greece .

Background/aim: Recent evidence suggests that survivin, a member of the inhibitors of apoptosis family that prevents cell death and regulates cell division is implicated in the pathogenesis of inflammatory bowel disease (IBD). The aim of the study was to identify a possible association between individual genetic variation, IBD susceptibility, and response to infliximab (IFX).

Material And Methods: The expression levels of survivin were detected in pathologic areas of fresh tissues and blood samples by real-time reverse transcriptase - polymerase chain reaction (RT-PCR) from IBD patients. Polymorphisms were identified using the polymerase chain reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Clinical and endoscopic response to IFX was evaluated by ileocolonoscopy performed at baseline and after 12-20 weeks of therapy with patients classified as either responders or nonresponders.

Results: No significant differences were found between survivin mRNA levels between patients and controls. Significant differences in both allele and genotype frequencies between Crohn's disease (CD) and ulcerative colitis (UC) patients and controls were found in -31C/G polymorphism. No association with IBD development was found for the -625G/C and -241T/C polymorphisms, since those polymorphisms were overrepresented in a healthy population. Additionally no significant association was found between -31C/G polymorphism and the clinical response of CD patients to IFX.

Conclusions: Survivin promoter polymorphism -31C/G might influence the susceptibility to IBD in the Greek population, but not the CD patient's response to anti-TNF drugs.
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http://dx.doi.org/10.1089/gtmb.2015.0036DOI Listing
June 2015

Optimized sedation improves colonoscopy quality long-term.

Gastroenterol Res Pract 2015 8;2015:195093. Epub 2015 Jan 8.

Academic Department of Gastroenterology, Laiko General Hospital, Medical School, Athens University, 11527 Athens, Greece.

Background. Quality monitoring and improvement is prerequisite for efficient colonoscopy. Aim. To assess the effects of increased sedation administration on colonoscopy performance. Materials and Methods. During Era 1 we prospectively measured four colonoscopy quality indicators: sedation administration, colonoscopy completion rate, adenoma detection rate, and early complications rate in three cohorts: cohort A: intention for total colonoscopy cases; cohort B: cohort A excluding bowel obstruction cases; cohort C: CRC screening-surveillance cases within cohort B. We identified deficiencies and implemented our plan to optimize sedation. We prospectively evaluated its effects in both short- (Era 2) and long-term period (Era 3). Results. We identified that sedation administration and colonoscopy completion rates were below recommended standards. After sedation optimization its use rate increased significantly (38.1% to 55.8% to 69.5%) and colonoscopy completion rate increased from 88.3% to 90.6% to 96.4% in cohort B and from 93.2% to 95.3% to 98.3% in cohort C, in Eras 1, 2, and 3, respectively. Adenoma detection rate increased in cohort C (25.9% to 30.6% to 35%) and early complications rate decreased from 3.4% to 1.9% to 0.3%. Most endoscopists increased significantly their completion rate and this was preserved long-term. Conclusion. Increased sedation administration results in long-lasting improvement of colonoscopy quality indicators.
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http://dx.doi.org/10.1155/2015/195093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306400PMC
February 2015
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