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Helicobacter pylori,gastric microbiota and gastric cancer relationship:Unrolling the tangle

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World Journal of Gastrointestinal Oncology 2022年第5期14卷 959-972页

作者： Christos Liatsos Apostolis Papaefthymiou Nikolaos Kyriakos Michail Galanopoulos Michael Doulberis Marios Giakoumis Evangelia Petridou Christos Mavrogiannis Theodore Rokkas jannis kountouras Department of Gastroenterology 401 General Military Hospital of AthensAthens 11525Greece Gastroenterology University Hospital of LarissaLarissa 41336Greece Division of Gastroenterology and Hepatology Medical University DepartmentKantonsspital AarauAarau 1234Switzerland Department of Microbiology “Agia Sofia”Paediatric HospitalGoudiAthens 11527Greece Gastrointestinal and Liver Unit Faculty of NursingKifissia General and Oncology HospitalKaliftakiN.Kifisia 14564Greece Gastroenterological Clinic Henry Dunant HospitalAthens 11525Greece Department of Internal Medicine Second Medical ClinicIppokration HospitalAristotle University of ThessalonikiThessaloniki 41336MacedoniaGreece

Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors,leading to inflammatory changes,dysbiosis and eventually gastric cancer.The normal gastric microbiota shows diversity,with Proteobacteria[Helicobacter pylori(H.pylori)belongs to this family],Firmicutes,Actinobacteria,Bacteroides and Fusobacteria being the most abundant phyla.Most studies indicate that H.pylori has inhibitory effects on the colonization of other bacteria,harboring a lower diversity of them in the stomach.When comparing the healthy with the diseased stomach,there is a change in the composition of the gastric microbiome with increasing abundance of H.pylori(where present)in the gastritis stage,while as the gastric carcinogenesis cascade progresses to gastric cancer,the oral and intestinal-type pathogenic microbial strains predominate.Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself.Successful H.pylori eradication is suggested to restore gastric microbiota,at least in primary stages.It is more than clear that Hp-I,gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll.Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H.pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.

关键词： Helicobacter pylori infection Gastric microbiota Gastric cancer Oncogenesis Dysbiosis Helicobacter pylori eradication

Comment on “Effect of biofilm formation by clinical isolates of Helicobacter pylori on the efflux-mediated resistance to commonly used antibiotics”

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World Journal of Gastroenterology 2017年第33期23卷 6194-6196页

作者： Evangelos I Kazakos Nick Dorrell Stergios A Polyzos Georgia Deretzi jannis kountouras Department of Medicine the Second Medical ClinicAristotle University of ThessalonikiIppokration Hospital Department of Pathogen Molecular Biology Faculty of Infectious and Tropical DiseasesLondon School of Hygiene and Tropical Medicine Department of Neurology Multiple Sclerosis UnitPapageorgiou General Hospital

Attaran et al[1] have recently shown that decreased susceptibility of established Helicobacter pylori(H. pylori) biofilms to specific antibiotics,was associated with the overtly enhanced transcription of two efflux pump genes,hp1165 and hef A,involved in specific resistance to tetracycline and multiple antibiotics,respectively. Apart from antibiotic exposure,secretion of multiple antimicrobial peptides,such as human β-defensins(hβDs),by the gastric epithelium upon Hp challenge,may act as early triggering events that positively impact biofilm formation and thus,antibiotic resistance. In this regard,we undertook genomic transcriptional studies using Hp 26695 strain following exposure to sublethal,similar to those present in the gastric niche,concentrations of hβDs in an attempt to provide preliminary data regarding possible mechanisms of immune evasion and selective sensitivity of Hp. Our preliminary results indicate that hβD exposure ignites a rapid response that is largely due to the activation of several,possibly interconnected transcriptional regulatory networks – origons-that ultimately coordinate cellular processes needed to maintain homeostasis and successful adaptation of the bacterium in the gastric environment. In addition,we have shown that both antibiotic and hβD resistance are mediated by dedicated periplasmic transporters,including the aforementioned efflux pump genes hp1165 and hef A,involved in active export of antibiotics from the cell membrane and/or,as recently suggested,substrate sensing and signalling. Furthermore,itappears that sublethal doses of hβDs may enhance biofilm formation by the sustained expression of,mainly,quorum sensing-related genes. In conclusion,we provide additional data regarding the role of specific innate immune molecules in antibiotic cross-resistance mechanisms that may deepen our understanding in the context of the development of novel eradication regimens.

关键词： Helicobacter pylori Human β-defensins Biofilm Antimicrobial resistance

Wireless capsule endoscopy in detecting small-intestinal polyps in familial adenomatous polyposis

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World Journal of Gastroenterology 2009年第48期15卷 6075-6079页

作者： Panagiotis Katsinelos jannis kountouras Grigoris Chatzimavroudis Christos Zavos Ioannis Pilpilidis Kostas Fasoulas George Paroutoglou Departmentof Endoscopy and Motility Unit Central HospitalThessalonikiGreece Second Departmentof Internal Medicine Aristotle University of ThessalonikiHippokration Hospital

AIM:To detect the prevalence of small bowel polyps by wireless capsule endoscopy(WCE)in patients with familial adenomatous polyposis(FAP).METHODS:We examined prospectively 14 patients with FAP to assess the location,size and number of small-intestinal polyps.Patients'age,sex,years of observation after surgery,type of surgery,duodenal polyps and colorectal cancer at surgery were analyzed.RESULTS:During WCE,polyps were detected in 9/14(64.3%)patients.Duodenal adenomatous polyps were found in nine(64.3%)patients,and jejunal and ileal polyps in seven(50%)and eight(57.1%),respectively.The Spigelman stage of duodenal polyposis was associated with the presence of jejunal and ileal polyps.Identification of the ampulla of Vater was not achieved with WCE.Importantly,the findings of WCE had no immediate impact on the further clinical management of FAP patients.No procedure-related complications were observed in the patients.CONCLUSION:WCE is a promising noninvasive new method for the detection of small-intestinal polyps.Further investigation is required to determine which phenotype of FAP is needed for surveillance with WCE.

关键词：小肠检测家族内镜胶囊无线肉性腺

Dissociating nonalcoholic steatohepatitis from hepatocellular carcinoma in obesity

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Hepatobiliary Surgery and Nutrition 2020年第1期9卷 73-76页

作者： Stergios A.Polyzos jannis kountouras Antonis Goulas Eleni Papakonstantinou Paraskevi Papaioannidou First Laboratory of Pharmacology School of MedicineAristotle University of ThessalonikiThessalonikiGreece Second Medical Clinic School of MedicineAristotle University of ThessalonikiThessalonikiGreece

Introduction The prevalence of obesity has increased over the last decades reaching epidemic proportions:39%of adults were overweight or obese in 2016 worldwide,according to World Health Association(https://www.***.int/news-room/fact-sheets/detail/obesity-and-overweight).Moreover,obesity is linked to metabolic syndrome(MetS)and related comorbidities,including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes mellitus(T2DM),cardiovascular disease(CVD)and malignancies,thus resulting in higher mortality for obese individuals(1).

关键词： obesity mortality nonalcoholic

Recent advances in the management of radiation colitis

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World Journal of Gastroenterology 2008年第48期14卷 7289-7301页

作者： jannis kountouras Christos Zavos Department of Gastroenterology Second Medical Clinic Aristotle University of Thessaloniki Ippokration Hospital

Radiation colitis, an insidious, progressive disease of increasing frequency, develops 6 mo to 5 years after regional radiotherapy for malignancy, owing to the deleterious effects of the latter on the colon and the small intestine. When dealing with radiation colitis and its complications, the most conservative modality should be employed because the areas of intestinal injury do not tend to heal. Acute radiation colitis is mostly self-limited, and usually, only supportive management is required. Chronic radiation colitis, a poorly predictable progressive disease, is considered as a precancerous lesion; radiation-associated malignancy has a tendency to be diagnosed at an advanced stage and to bear a dismal prognosis. Therefore, management of chronic radiation colitis remains a major challenge owing to the progressive evolution of the disease, including development of fibrosis, endarteritis, edema, fragility, perforation, partial obstruction, and cancer. Patients are commonly managed conservatively. Surgical intervention is difficult to perform because of the extension of fibrosis and alterations in the gut and mesentery, and should be reserved for intestinal obstruction, perforation, fistulas, and severe bleeding. Owing to the difficulty in managing the complications of acute and chronic radiation colitis, particular attention should be focused onto the prevention strategies. Uncovering the fibrosis mechanisms and the molecular events underlying radiation bowel disease could lead to the introduction of new therapeutic and/or preventive approaches. A variety of novel, mostly experimental, agents have been used mainly as a prophylaxis, and improvements have been made in radiotherapy delivery, including techniques toreduce the amount of exposed intestine in the radiation field, as a critical strategy for prevention.

关键词：发散性结肠炎急性慢性预防措施肠梗阻穿孔

Impact of periampullary diverticula on the outcome and fluoroscopy time in endoscopic retrograde cholangiopancreatography

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Hepatobiliary & Pancreatic Diseases International 2013年第4期12卷 408-414页

作者： Panagiotis Katsinelos Grigoris Chatzimavroudis Kostas Tziomalos Christos Zavos Athanasios Beltsis Georgia Lazaraki Sotiris Terzoudis jannis kountouras Department of Endoscopy and Motility Unit G. Gennimatas General Hospital School of Medicine Aristotle University of Thessaloniki Ippokration HospitalThessaloniki Greece Department of Internal Medicine School of Medicine Aristotle University of Thessaloniki Ippokration HospitalThessaloniki Greece

BACKGROUND: It is unclear whether the presence of periampullary diverticula (PAD) affects technical success and complication rates during endoscopic retrograde cholangio- pancreatography (ERCP). Moreover, the impact of PAD on fluoroscopy duration is still unknown. The present study aimed to investigate the success rate and difficulty of common bile duct (CBD) cannulation, post-procedure complications and fluoroscopy duration in patients with and without PAD. METHODS: Patients from January 2008 to December 2010 with PAD (group A) and without PAD (group B) and similar indications for therapeutic ERCP were prospectively compared. The comparison included patient characteristics, findings of ERCP, and details of procedure and fluoroscopy time. The influence of papilla’s location with respect to the diverticulum on procedure was also investigated. RESULTS: A total of 428 consecutive patients who had undergone therapeutic ERCP for similar indications were divided in two groups according to the presence (group A, 107 patients) or absence (group B, 321 patients) of PAD. The mean age and ASA score of the patients with PAD were significantly higher than those patients without PAD. The main indication was choledocholithiasis. Successful final CBD cannulation was achieved in 97.20% of the patients in group A vs 99.69% in group B (P=0.05). CBD diameter, number of stones and the largest stone size were significantly higher in group A thangroup B (P<0.001). Complete clearance of the CBD after the first attempt was achieved in 85.86% and 94.75% of the patients in groups A and B, respectively (P=0.03). In both groups, the time needed to complete the procedure and fluoroscopy time was significantly longer in patients with PAD (22.87 vs 18.99 minutes, P<0.001; 76.51 vs 47.42 seconds, P<0.001). There was no significant difference between the two groups in the complication rate. The type of papilla’s location with respect to the diverticulum did not influence the total cannulation rate and post-procedure complications. CONCLU

关键词： endoscopic retrograde cholangiopancreatography anatomy ampulla of Vater

Endoclipping treatment of life-threatening rectal bleeding after prostate biopsy

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世界胃肠病学杂志：英文版 2009年第9期15卷 1130-1133页

作者： Panagiotis Katsinelos jannis kountouras Georgios Dimitriadis Grigoris Chatzimavroudis Christos Zavos Ioannis Pilpilidis George Paroutoglou George Germanidis Kostas Mimidis Department of Endoscopy and Motility Unit Central Hospital54635 ThessalonikiGreece Department of Gastroenterology Second Medical ClinicAristotle Universityof ThessalonikiIppokration Hospital54635 ThessalonikiGreece First Department of Urology Aristotle University of ThessalonikiCentral Hospital54635ThessalonikiGreece

Rectal bleeding is frequently seen in patients undergoing transrectal ultrasound(TRUS)-guided multiple biopsy of the prostate,but is usually mild and stops spontaneously.We report what is believed to be the first case of life-threatening rectal bleeding following this procedure,which was successfully treated by endoscopic intervention through placement of three clips on the sites of bleeding.This case emphasizes endoscopic intervention associated with endoclipping as a safe and effective method to achieve hemostasis in massive rectal bleeding after prostate biopsy.Additionally,current data on the complications of the TRUS-guided multiple biopsy of the prostate and the options for treating fulminant rectal bleeding, a consequence of this procedure,are described.

关键词：直肠前列腺穿刺活检后出血治疗生命前列腺穿刺活检术威胁直肠出血超声引导

Role of autophagy in gastric carcinogenesis

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1244-1262页

作者： Apostolis Papaefthymiou Gregory Christodoulidis Apostolos Koffas Michael Doulberis Stergios A Polyzos Anastasios Manolakis Spyros Potamianos Andreas Kapsoritakis jannis kountouras Department of Gastroenterology University Hospital of LarissaLarissa 41110ThessalyGreece First Laboratory of Pharmacology Aristotle University of ThessalonikiThessaloniki 54124MacedoniaGreece Department of Medicine Second Medical ClinicAristotle University of ThessalonikiIppokration HospitalThessaloniki 54642MacedoniaGreece Department of Surgery University Hospital of LarissaLarissa 41110ThessalyGreece Division of Gastroenterology and Hepatology Medical University DepartmentKantonsspital AarauAarau 5001Switzerland

Gastric cancer represents a common and highly fatal malignancy,and thus a pathophysiology-based reconsideration is necessary,given the absence of efficient therapeutic regimens.In this regard,emerging data reveal a significant role of autophagy in gastric oncogenesis,progression,metastasis and chemoresistance.Although autophagy comprises a normal primordial process,ensuring cellular homeostasis under energy depletion and stress conditions,alterations at any stage of the complex regulatory system could stimulate a tumorigenic and promoting cascade.Among others,Helicobacter pylori infection induces a variety of signaling molecules modifying autophagy,during acute infection or after chronic autophagy degeneration.Subsequently,defective autophagy allows malignant transformation and upon cancer establishment,an overactive autophagy is stimulated.This overexpressed autophagy provides energy supplies and resistance mechanisms to gastric cancer cells against hosts defenses and anticancer treatment.This review interprets the implicated autophagic pathways in normal cells and in gastric cancer to illuminate the potential preventive,therapeutic and prognostic benefits of understanding and intervening autophagy.

关键词： Gastric cancer Autophagy Helicobacter pylori Chemoresistance Prognosis

Partially covered vs uncovered sphincterotome and postendoscopic sphincterotomy bleeding

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World Journal of Gastroenterology 2010年第40期16卷 5077-5083页

作者： Panagiotis Katsinelos George Paroutoglou jannis kountouras Grigoris Chatzimavroudis Christos Zavos Sotiris Terzoudis Taxiarchis Katsinelos Kostas Fasoulas George Gelas George Tzovaras Ioannis Pilpilidis Department of Endoscopy and Motility Unit Medical School Aristotle University of Thessaloniki G. Gennimatas General Hospital Department of Gastroenterology University Hospital of Thessaly 2nd Department of Internal Medicine Medical School Aristotle University of Thessaloniki Ippokration Hospital

AIM: To prospectively compare partially covered vs uncovered sphincterotome use on post-endoscopic biliary sphincterotomy (ES) hemorrhage and other complications. METHODS: All patients referred for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to undergo ES either with a partially covered or an uncovered sphincterotome. Both patient and technical risk factors contributing to the development of post-ES bleeding were recorded and analyzed. The characteristics of bleeding was recorded during and after ES. Other complications were also compared. RESULTS: Three-hundred and eighty-seven patients were recruited in this study; 194 patients underwent ES with a partially covered sphincterotome and 193 with conventional uncovered sphincterotome. No statistical difference was noted in the baseline characteristics and risk factors for post-ES induced hemorrhage between the 2 groups. No significant difference in the incidence and pattern of visible bleeding rates was found between the 2 groups (immediate bleeding in 24 patients with the partially covered sphincterotome vs 19 patients with the uncovered sphincterotome, P = 0.418). Delayed bleeding was observed in 2 patients with a partially covered sphincterotome and in 1 patient with an uncovered sphincterotome (P = 0.62). No statistical difference was noted in the rate of other complications. CONCLUSION: The partially covered sphincterotome was not associated with a lower frequency of bleeding. Also, there was no difference in the incidence of other significant complications between the 2 types of sphincterotome.

关键词： Sphincterotome Endoscopic sphincterotomy Hemorrhage Complications