This document discusses Helicobacter pylori infection. It begins with a summary of the discovery of H. pylori, including Giulio Bizzozero's initial description in 1892 and Robin Warren and Barry Marshall's cultivation of H. pylori in 1982. It then covers the epidemiology of H. pylori infection, indications for treatment, methods for diagnosing infection, treatments for infection, and the role of H. pylori eradication in preventing gastric cancer. Key points include that over 50% of the world's population is infected with H. pylori and treatment aims to cure ulcers and reduce cancer risk. Diagnosis involves non-invasive tests like serology or breath tests
Helicobacter pylori and Peptic Ulcer diseaseDiaa Srahin
Case Study
Clinical Case Summary
History
Helicobacter pylori
Biochemical characteristics
Transmission
Epidemiology
Global incidence of H. pylori infection
risk factors for acquisition of H.pylori
Immune responses
Pathogenesis
Helicobacter pylori Virulence Factors
Clinical Presentation
Complications
Peptic Ulcer
Diagnosis
Treatment
Prevention
Laboratory diagnosis of H. Pylori infection, Ola ElgaddarOla Elgaddar
A short presentation for the different laboratory techniques used in diagnosing Helicobacter Pylori infection. A special focus is given for the diagnostic performance of every test.
Helicobacter pylori associated Peptic ulcer diseaseS M Ali Hasan
Evidence-based clinical practice guidelines for H. pylori associated peptic ulcer disease based on
Japanese society of Gastroenterology, 2015
American College of Gastroenterology, 2017
The Maastricht V/Florence Consensus Report, 2018
Helicobacter pylori and Peptic Ulcer diseaseDiaa Srahin
Case Study
Clinical Case Summary
History
Helicobacter pylori
Biochemical characteristics
Transmission
Epidemiology
Global incidence of H. pylori infection
risk factors for acquisition of H.pylori
Immune responses
Pathogenesis
Helicobacter pylori Virulence Factors
Clinical Presentation
Complications
Peptic Ulcer
Diagnosis
Treatment
Prevention
Laboratory diagnosis of H. Pylori infection, Ola ElgaddarOla Elgaddar
A short presentation for the different laboratory techniques used in diagnosing Helicobacter Pylori infection. A special focus is given for the diagnostic performance of every test.
Helicobacter pylori associated Peptic ulcer diseaseS M Ali Hasan
Evidence-based clinical practice guidelines for H. pylori associated peptic ulcer disease based on
Japanese society of Gastroenterology, 2015
American College of Gastroenterology, 2017
The Maastricht V/Florence Consensus Report, 2018
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease, particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC).
Risk factors for progression of chronic HBV include the following :
Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Alcohol use
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patient’s immune response with immunotherapeutic interventions is needed for the best prognosis. The prevention of HCC often includes the use of antiviral treatment using pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.
HBV infection can be self-limited or chronic. No specific therapy is available for persons with acute hepatitis B; treatment is supportive.
Helicobacter Pylori infect more than 50% of worlds population.HP causes gastritis,PUD,gastric cancer and MALT lymphoma.Variable invasive and noninvasive diagnostic modilities are available.Eradication of H.Pylori is possible with proper therapy.
basics about chronic liver disease for a pediatrician. fast and easy guide to common causes of chronic liver diseases in children
Please leave a comment if you like it..
The lecture was presented during the 13th annual conference of KLRC held in Alexandria 15 -17 August 2017
The lecture was directed to describe the current situation of H.Pylori infection in middle east ,particularly in Egypt , and to put some spotlights on the current regimens of treatment , and the situation of antibiotic resistance in Egypt and its impact on treatment choice
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease, particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC).
Risk factors for progression of chronic HBV include the following :
Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Alcohol use
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patient’s immune response with immunotherapeutic interventions is needed for the best prognosis. The prevention of HCC often includes the use of antiviral treatment using pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.
HBV infection can be self-limited or chronic. No specific therapy is available for persons with acute hepatitis B; treatment is supportive.
Helicobacter Pylori infect more than 50% of worlds population.HP causes gastritis,PUD,gastric cancer and MALT lymphoma.Variable invasive and noninvasive diagnostic modilities are available.Eradication of H.Pylori is possible with proper therapy.
basics about chronic liver disease for a pediatrician. fast and easy guide to common causes of chronic liver diseases in children
Please leave a comment if you like it..
The lecture was presented during the 13th annual conference of KLRC held in Alexandria 15 -17 August 2017
The lecture was directed to describe the current situation of H.Pylori infection in middle east ,particularly in Egypt , and to put some spotlights on the current regimens of treatment , and the situation of antibiotic resistance in Egypt and its impact on treatment choice
How Helicobacter Pylori can cause gastric ulcerations and how this can lead t...Pırıl Erel
Analysis and disccusion of how Helicobacter Pylori (H.pylori) developed genetically and physically as a bacterium to be effective in affecting host cells. It has successfully affected 50% of host cells within the human population. Retrospective research of genomic advances and interactions of H.pylori migration between old and new world.
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H. Pylori as an etiological factor in Peptic ulcer disease.Donpir Cazorla
Peptic ulcer disease(PUD) is one of the most common gastroenterological diseases warranting GP consultation. This presentation takes a deep look at H. Pylori; The structure of this bacterium and it's patho-physiology in Peptic ulcer disease(causes about 80-85%).
Ulcers are the areas of degeneration and necrosis of gastro intestinal mucosa exposed to acid of the alimentary tract that is exposed to hydrochloric acid and pepsin they occur most commonly (98-99%) in either the duodenum or the stomach in the ratio 4:1
CHRONIC DYSPEPSIA
Seminar Prepared by :-
Ali Abdulazeem
Shilan Adnan Abdulrahman
Alaa Shamil
Guldan Hameed
Internal Medicine
College of Medicine - University of Kirkuk
Presentazione a cura del Professor Cesare Cremon - M.A.S.T.E.R. ECM in Gastroenterologia: Focus on: Microbiota e dintorni - Fondazione Santa Lucia - Roma
GASBARRINI A. Nutrizione Clinica e Gastroenterologia. ASMaD 2017Gianfranco Tammaro
PROF. ANTONIO GASBARRINI - Convegno "Il Presente ed il Futuro della Nutrizione Clinica" - 24/03/2017 - Sala Rita Levi Montalcini - Ospedale S.Eugenio - ROMA
Sito ASMaD: http://www.asmad.net
Canale Youtube: https://youtu.be/FYlsQzE8xfk
Description of various ultrasound features of benign and suspicious thyroid nodules with multiple ultrasound systems for risk stratification of malignancy.
Description of different ultrasound features of carpal tunnel syndrome before and after carpal tunnel release including Doppler imaging and elastography
Doppler ultrasound of visceral arteriesSamir Haffar
Doppler ultrasound of different diseases of visceral arteries including arterial stenosis and occlusion, arterial aneurysm, artrial pseudoaneurysm, arterio-venous fistula, artrial dissection, and abdominal vascular compression syndromes
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
2. Helicobacter pylori infection
Discovery of H. pylori
Epidemiology of H. pylori
Indications for treatment
Diagnosis of infection
Treatment of infection
Prevention of gastric cancer
3. Giulio Bizzozero (1846 – 1901)
Italian pathologist
• Desribed for first time presence of
helicobacters in stomach of dogs
• Communicated his discovery to Turin
Medial Academy (18th March 1892)
• Spirilli described by Bizzozzero were
presumably H. beilmannii or H. felis
Figura N et al. In Marshall BJ, ed. Helicobacter pioneers.
Victoria, Australia: Blackwell, 2002.
4. Bizzozero’s drawing
Bacteria live in acid producing cells
These bacteria must be acid tolerant or must turn off acid secretion
Figura N et al. In Marshall BJ, ed. Helicobacter pioneers.
Victoria, Australia: Blackwell, 2002.
5. First detailed histological & US
ultrastructural studies on human HP
• Done by Steer in Southampton in 1975
• Spiral bacteria closely apposed to mucus secreting cells
bacteria possessed at least one flagellum
• Polymorphonuclear leucocytes migrated through gastric
mucosa, presumably in response to bacteria
• Culture of endoscopic biopsy yielded only
Pseudomonas aeruginosa (not a spiral organism)
Steer HW. J Clin Pathol 1975 ; 28 : 639 – 46.
6. Royal Perth hospital, Perth, Western Australia
1982
• R Warren Expert in gastric pathology & bacterial
staining in pathological specimens
• B Marshall Registrar in training
Learning gastroenterology for 6 months
• JAArmstrong Head of electron microscopy unit
• CS Goodwin Head of microbiology department
Goodwin C S. Gut 1993 ; 34 : 293 – 294.
7. Koch's postulates (1890)
Causal relationship between a microbe & a disease
Microorganism must be present in every case of disease
Microorganism must be isolated from diseased organism
& grown in pure culture
Cultured microorganism should cause disease when
introduced into a healthy organism
Microorganism must be recoverable from experimental
infected host
Koch R. J Hyg Inf 1893 ; 14 : 319 – 333.
8. Protocol for H. pylori culture
Gastric biopsy from 100 patients started March 1982
The first 34 cultures
Spiral bacteria seen in Gram stain in six
Spiral bacteria were not cultured
Incubation was limited to 48 hours
The 35th culture
Incubating during Easter holiday (5 days in Australia)
Pure growth of 1 mm transparent colonies
H. pylori had been finally cultured (14 April 1982)
Goodwin C S. Gut 1993 ; 34 : 293 – 294.
9. Marshall's stomach biopsy
Notorious picture
Marshall BJ et al. Attempt to fulfill Koch's postulates for Campylobacter Pylori.
Med J Aust 1985 ; 142 : 436 – 439.
Silver stain of HP on gastric epithelial cells (x1000)
Marshall's stomach biopsy taken 8 days after he drank culture of HP
10. Warren & Marshall receiving the Nobel Prize
from the King Carl XVI Gustaf of Sweden
Stockholm Concert Hall, 10 December 2005
Robin Warren Barry Marshall
11. Helicobacter pylori infection
Discovery of H. pylori
Epidemiology of H. pylori
Indications for treatment
Diagnosis of infection
Treatment of infection
Prevention of gastric cancer
12. Morphology of H. pylori
Micro-aerophilic
Gram-negative
Slow growing
Spiral-shaped
Flagellated
13. Prevalence of H. pylori infection
Most common chronic bacterial infection of humans
100
80
60
40
20
0
% individuals infected
0 10 20 30 40 50 60 70 80 Age (years)
Marshall 1994
Developing
countries
Western
countries
'Carrier state' from
childhood infection
(before 1945)
Rapid acquisition
in childhood
≈ 50% of
world’s population
14. Natural history of H. pylori infection
Longo DL et al. Harrison’s gastroenterology & hepatology.
McGraw-Hill, New York, USA, 2010.
16. H. Pylori infection & gastric acid secretion
Kuipers EJ. Gut 2006 ; 55 : 1217 – 1221.
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
Antral predominant gastritis
Duodenal ulcer
Non-ulcer dyspepsia
Corpus predominant gastritis
Gastric ulcer
Premalignant gastric lesions
Pattern of gastritis determine disease outcomes
17. Conditions associated with PUD
Duodenal ulcer Gastric ulcer
Sleisenger & Fordtran’s gastrointestinal & liver disease.
Saunders-Elsevier, Philadelphia, PA , USA, 9th edition , 2010.
H. pylori infection & NSAID use often coexist
18. Helicobacter pylori infection
Discovery of H. pylori
Epidemiology of H. pylori
Indications for treatment
Diagnosis of infection
Treatment of infection
Prevention of gastric cancer
19. Indications for treatment of H. pylori infection
Gastric diseases
• Past or present duodenal/gastric ulcer
• Dyspepsia
• Atrophic gastritis
• Low grade MALT lymphoma: early stages (Lugano I/II)
• Following resection of gastric cancer
• First-degree relatives with gastric cancer
• Patient’s wishes
* WGO global guideline. J Clin Gastroenterol 2011 ; 45 : 383 – 388.
** Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
20. H. pylori & NSAID or low-dose aspirin
• HP & NSAID use are independent risk factors for PUD
• Naïve NSAID users Beneficial to eradicate HP
• Long-term NSAID No clear benefit
Eradication less effective than PPI
PPI as well as HP eradication
• Low dose aspirin Eradication in pts with PU history
Malfertheiner P et al. Management of HP infection: Maastricht IV/Florence consensus report.
Gut 2012 ; 61: 646 – 664.
21. H pylori & GERD
• Epidemiological studies show negative association between
prevalence of HP & severity of GERD & incidence of
esophageal adenocarcinoma (Grade A)
• H pylori eradication does not exacerbate pre-existing GERD
or affect treatment efficacy (Grade A)
Malfertheiner P et al. Management of HP infection: Maastricht IV/Florence consensus report.
Gut 2012; 61: 646 – 664.
22. H pylori & long-term treatment with PPI
• Long-term treatment with PPIs in HP-positive patients
associated with development of corpus-predominant
gastritis leading to atrophic gastritis (Grade A)
• Eradication of HP in pts receiving long-term PPIs heals
gastritis & prevents progression to atrophic gastritis but
no evidence of reducing risk of gastric cancer (Grade A)
Malfertheiner P et al. Management of HP infection: Maastricht IV/Florence consensus report.
Gut 2012; 61: 646 – 664.
23. Malfertheiner P et al. Management of HP infection: Maastricht IV/Florence consensus report.
Gut 2012 ; 61: 646 – 664.
Association
Unexplained iron deficiency anemia
Idiopathic thrombocytopenic purpura (ITP)
Vitamin B12 deficiency
Further research
Asthma & atopy
Obesity & related illnesses
Cardiovascular disorders
Neurological disorders
No association
Indications for treatment of H. pylori infection
Extra-gastric diseases
24. Helicobacter pylori infection
Discovery of H. pylori
Epidemiology of H. pylori
Indications for treatment
Diagnosis of infection
Treatment of infection
Prevention of gastric cancer
25. Diagnosis of H pylori infection
Tests Sensitivity Specificity
Non-endoscopic methods
Serology
Validated ELISA IgG
85 – 92%
79 – 83%
Not for confirming eradication
Urea breath test 95% 96%
Fecal antigen test
ELIZA - monoclonal
95% 94%
Endoscopic methods
Rapid urease test
1 antrum & 1 corpus
98% 99%
Histology
1 antrum & 1 corpus
> 95% > 95%
Culture 70 – 90% 100%
WGO global guideline. J Clin Gastroenterol 2011 ; 45 : 383 – 388.
Malfertheiner P et al. Gut 2012; 61: 646 – 664.
26. Serology for diagnosis of HP
• Chronic infection IgG detection only
• Favored method ELISA
• Some kits with accuracy > 90% Use validated tests only
• Not affected by low bacterial load Use of antibiotics
Use of antisecretory
Bleeding ulcer
Gastric atrophy
Gastric malignancies
Malfertheiner P et al. Gut 2012; 61: 646 – 664.
27. Mégraud F. Presse Med. 2010 ; 39 : 815 – 822.
Malfertheiner P et al. Gut 2012; 61: 646 – 664.
Antibiotics Stopped for at least 4 weeks
PPIs Stopped for 14 days
H2RA Stopped for 7 days
Antacids Not stopped
UBT, monoclonal stool test, & culture
No role for serology to confirm eradication
28. Urea breath test / C13 and C14
Mégraud F. Presse Med. 2010 ; 39 : 815 – 822.
29. Rapid Urease Test (RUT)
Available RUT kits
CLO test
HpFast
HUT-test
Pronto Dry
Pyloritek
Overall performance of different tests comparable
30. Helicobacter pylori infection
Discovery of H. pylori
Epidemiology of H. pylori
Indications for treatment
Diagnosis of infection
Treatment of infection
Prevention of gastric cancer
31. Clinical trial of H. pylori therapy
Graham DY & Dore MP. Helicobacter 2011 ; 16 : 343 – 345.
100% or near 100% success expected
No placebo response
Failure almost always explainable: Resistance – Flawed regimen
32. Grading system of H. pylori therapy
Graham DY et al. Helicobacter 2007 ; 12 : 275 – 278.
Grade Cure rate (ITT) Score
A ≥ 95% Excellent
B 90 – 94 % Good
C 85 – 89 % Acceptable
D 81 – 84 % Poor
F
≤ 80% Unacceptable
Similar to grade performance of school children
Failed
33. Bacterial factors
Primary resistance to antibiotics
Bacterial load in stomach
Bacterial coccoid forms
cagA status (negative)
vacA alleles status (s2m2 allele)
dup A status*
Factors affecting H. pylori eradication success
* dup: duodenal ulcer promoting
Zullo A et al. J Clin Gastroenterol 2012 ; 46 : 259 – 261.
Host factors
Compliance to therapy
Gastric acid hypersecretion
Genetic polymorphism of CYP 450
Gastroduodenal disease (NUD)
Gastritis pattern (pangastritis)
Obesity
Smoking
34. H. pylori resistance to antibiotics
• Clarithromycin Not overcome by increasing dose & duration
‘all or none’ Should not be used if prevalence > 15 – 20%
• Levofloxacine Not overcome by increasing dose & duration
‘all or none’ Rapidly increasing worldwide
• Metronidazole Overcome by increasing dose & duration
‘not all or none’ Should not be used if prevalence > 40%
• Amoxicillin Rare in most regions
• Tetracycline Rare in most regions
• Bismuth Does not occur
Graham DY et al. Drugs 2008 ; 68 : 725 – 736.
36. H. Pylori & antibiotic resistance
• Cross-resistance in each family of antibiotics
Resistance to clarithromycin → resistance to all macrolides
Resistance to levofloxacin → resistance to all fluoroquinolones
• No cross-resistance between different families of antibiotics
• Important to use compound indicated to get good results
Clarithromycin for macrolides
Tetracycline HCl and not doxycycline
Levofloxacin but not ciprofloxacin for fluoroquinolones
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
37. Phenotypical antibiotic resistance & HP
Bigger JW. Lancet 1944 ; 247 : 497 – 500.
Scott D et al. Gut 1998 ; 43(Suppl 1): S56 – S60.
Graham et al. Gut 2010 ; 59 : 1143 – 1153.
pH 4 – 8: H. pylori survives
pH 4 – 6: Non-dividing H. pylori – Phenotypical resistance
pH 6 – 8: Dividing H. pylori – Susceptible to AMO or CLA
38. Difficulties associated with cure of H. pylori
• Development of H pylori resistance to many agents:
Metronidazole, clarithromycin & fluoroquinolones
• Huge number of HP organisms present in the stomach,
which produces an inoculum effect
• H. pylori organisms can reside in variety of niches:
Intracellularly or in highly acidic gastric mucus gel layer
• High rate of reinfection in developing countries
Rimbara E. et al. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
H. pyori, like tuberculosis, requires treatment with
multiple drugs for long duration
39. Annual recurrence of H. pylori after successful
eradication in developing countries
Each bar represents a different study
Recurrence of original infection or reinfection with new strain
Rimbara E. et al. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
40. Optimal antimicrobial therapies
• Dosage
• Dosing intervals
• Formulation
• Route of administration
• Duration of therapy
Establish parameters that will provide the best
outcome from a particular regimen:
Rimbara E. et al. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
41. Treatment of H. pylori infection
First line treatment
Standard triple therapy
Sequential therapy
Concomitant therapy
Sequential-concomitant therapy
Bismuth quadruple therapy
Legacy triple therapy
Five plus five day therapy
Non-bismuth quadruple therapy
Hybrid therapy
Underutilized in practice
Second line treatment (one treatment failure)
Levofloxacin triple therapy
Third line treatment (at least 2 treatment failures)
Culture-guided therapy
High-dose dual PPI therapy
Furazolidone quadruple therapy
Rifabutin-based triple therapy
Recommended
Empirical
Empirical
Empirical – Last resort
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
42. Standard triple therapy (PAC)
Most widely used & approved therapy
• PPI Standard dose, bid
• Amoxicillin 1 g, bid
• Clarithromycin 500 mg, bid
For 7 – 10 – 14 days
Standard triple therapy without prior susceptibility testing
should be abandoned when Clari-R > 15 – 20%
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
44. Treatment success for triple therapy
intention-to-treat analysis (ITT)
Line at 80% treatment success
Demarcation between acceptable & unacceptably success rate
Each bar represents a different study
Graham DY & Fischbach L. Gut 2010 ; 59 : 1143 – 1153.
45. Improving standard triple therapy (PAC)
• Increase dose of PPI
Esomeprazole 40 mg bid increases eradication by 8 – 12%
• Increase length of treatment
10-day treatment Increases eradication by 4%
14-day treatment Increases eradication by 5 – 6%
• Adjuvant treatment Lactoferrin – S. boulardii
Promising results
More studies needed
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
46. • PPI Standard dose, bid
• Metronidazole 500 mg, bid
• Clarithromycin 500 mg, bid
For 7 – 10 – 14 days
PAC & PMC regimens are equivalent
Should not be used if metronidazole resistance > 40%
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
Standard triple therapy (PMC)
Most widely used & approved therapy
47. Sequential therapy
‘‘five plus five’’ day therapy
• 1st five days PPI (standard dose, bid)
Amoxicillin (1 g bid)
• 2nd five days PPI (standard dose, bid)
Clarihromycin (500 mg, bid)
Metronidazole/Tinidazole (500 mg, bid)
For 10 days
Gisbert JP et al. J Clin Gastroenterol 2010 ; 44 : 313 – 325.
Indicated in clarithromycin or nitroimidazole resistance strains
No indicated in dual clarithromycin & metronidazole resistance
48. Sequential versus standard triple therapy
15 RCTs – ITT – Random effect model
Gisbert JP et al. J Clin Gastroenterol 2010 ; 44 : 313 – 325.
Eradication rate: 76.7% (75 – 79%) versus 91.7% (90 – 93%)
49. Concomitant therapy
“Non-bismuth quadruple therapy”
• PPI Standard dose, bid
• Amoxicillin 1 g, bid
• Clarithromycin 500 mg, bid
• Metronidazole/Tinidazole 500 mg, bid
Rimbara E & Graham DY. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
For 10 – 14 days
No indicated in high prevalence of Clari-R (> 20 – 30%)
No indicated in dual clarithromycin & metronidazole resistance
50. Concomitant therapy for treatment of H pylori
Meta-analysis – 15 RCTs (1723 pts) – Random effect
Gisbert J P et al. Aliment Pharmacol Ther 2011 ; 34 : 604 – 617.
51. Sequential-concomitant therapy
‘‘Hybrid therapy’’
• 1st seven days PPI (standard dose, bid)
Amoxicillin (1 g, bid)
• 2nd seven days PPI (standard dose, bid)
Amoxicillin (1 g, bid)
Clarihromycin (500 mg, bid)
Metronidazole/Tinidazole (500 mg, bid)
Hsu PI et al. Gastroenterology 2010 ; 138 (Suppl. 1), S111.
For 14 days
Treatment success (117 patients): 97% (ITT) – 99% (PP)
High efficacy in dual clarithromycin & metronidazole resistance
52. Bismuth quadruple therapy (BMT)
Underutilized in clinical practice
• PPI Standard dose, bid
• Bismuth subcitrate 420 mg, qid
• Metronidazole/Tinidazole 500 mg, tid
• Tetracycline 500 mg, qid
For 10 – 14 days
Highly effective: eradication rate 92%
Highly cost effective
Rimbara E & Graham DY. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
53. Treatment regimen according to areas of Clari-R
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
1st line
PPI-Amoxicillin-Clarithro
Bismuth quadruple
Bismuth quadruple
Sequential or Concomitant
Region with low Clari-R
< 20%
Region with high Clari-R
> 20%
54. Confirmation of eradication for H pylori
• Indications H. pylori–associated ulcer
Persistent symptoms in dyspepsia
Gastric MALT lymphoma
Resection for early gastric cancer
• Methods Urea breath test or fecal antigen test
Endoscopy if it is required
Mégraud F. Presse Med. 2010 ; 39 : 815 – 822.
McColl KEL. N Engl J Med 2010 ; 362 : 1597 – 1604.
55. Treatment of H pylori-positive peptic ulcer
• Uncomplicated DU
Prolongs PPI not recommended after HP treatment (Grade A)
• GU & complicated DU
Prolongs PPI treatment is recommended (Grade A)
• Bleeding ulcer
HP eradication started at introduction of oral feeding (Grade A)
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
56. Treatment of H. pylori infection
First line treatment
Standard triple therapy
Sequential therapy
Concomitant therapy
Sequential-concomitant therapy
Bismuth quadruple therapy
“legacy triple therapy”
“five plus five day therapy”
“non-bismuth quadruple therapy”
“hybrid therapy”
underutilized in practice
Second line treatment (one treatment failure)
Levofloxacin triple therapy
Third line treatment (at least 2 treatment failures)
Culture-guided therapy
High-dose dual PPI therapy
Furazolidone quadruple therapy
Rifabutin-based triple therapy
Recommended
Empirical
Empirical
Empirical – Last resort
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
57. Levofloxacin-based triple therapy
Second line therapy
• PPI Standard dose, bid
• Amoxicillin 1 g, bid
• Levofloxacin 500 mg, qd
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
For 10 – 14 days
Rising rates of levofloxacin resistance
58. Treatment regimen according to areas of Clari-R
Region with low Clari-R
< 20%
Region with high Clari-R
> 20%
1st line
PPI-Amoxicillin-Clarithro
Bismuth quadruple
Bismuth quadruple
Sequential or Concomitant
2nd line*
Bismuth quadruple
PPI-Amoxicillin-Levofoxacin
PPI-Amoxicillin-Levofoxacin
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
* Regimen should not include antibiotics given previously
59. Treatment of H. pylori infection
First line treatment
Standard triple therapy
Sequential therapy
Concomitant therapy
Sequential-concomitant therapy
Bismuth quadruple therapy
“legacy triple therapy”
“five plus five day therapy”
“non-bismuth quadruple therapy”
“hybrid therapy”
underutilized in practice
Second line treatment (one treatment failure)
Levofloxacin triple therapy
Third line treatment (at least 2 treatment failures)
Culture-guided therapy
High-dose dual PPI therapy
Furazolidone quadruple therapy
Rifabutin-based triple therapy
Recommended
Empirical
Empirical
Empirical – Last resort
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
60. Culture-guided therapy
Recommended third line therapy
• PPI Standard dose, bid
• Bismuth 2 tablets, qid
• 1st antibiotic Selected by antimicrobial sensitivity tests
• 2nd antibiotic Selected by antimicrobial sensitivity tests
For 10 – 14 days
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
61. Susceptibility testing
• Culture & standard susceptibility testing (preferable)
Practical for Clarithromycin & Levofloxacin resistance
Metronidazole susceptibility testing lacks reproducibility
• Molecular tests (if culture not possible)
Detect mutations in HP genome that result in resistance
RT PCR/nested PCR on gastric biopsies (or stool specimens)
Practical for Clari-R & possibly fluoroquinolone resistance
• Fluorescence in situ hybridization (FISH)
On gastric biopsies
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
62. High-dose dual PPI therapy
Empirical third line therapy
• PPI (high dose) Omeprazole 40 mg, qid
or
Lansoprazole 30 mg, qid
• Amoxicillin 500 mg, bid
Rimbara E & Graham DY. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
For 14 days
Studies needed to confirm the success seen in Japan
63. Furazolidone-based quadruple therapy
Empirical third line therapy
• PPI Standard dose, bid
• Bismuth subcitrate 420 mg, qid
• Tetracyclin 500 mg, qid
• Furazolidone 100 mg, tid
Graham DY & Lu H. Saudi J Gastroenterol 2012 ; 18 : 1 – 2.
For 10 – 14 days
64. Furazolidone
• Produced commercially since 1955
• Antibacterial & antiprotozoal in human & veterinary medicine
• No longer marketed in US since 2005 (market too small)
• No approved by the EMA1 for human medicine or animal use
• Classified by the IARC2 as group 3 drug in 1998
• Monamine oxidase inhibitor & may interact with food & drugs
• Variable resistance: 1 – 25 % in Iran & 0 – 40% in China
1 EMA: European Medicines Agency
2 IARC: International Agency for Research on Cancer
Graham DY & Lu H. Saudi J Gastroenterol 2012 ; 18 : 1 – 2.
Zullo A et al. Saudi J Gastroenterol 2012 ; 18 : 11 – 17.
66. Rifabutin-based triple therapy
Empirical third line therapy – Drug of last resort
• PPI Standard dose, bid
• Amoxicillin 1 g, bid
• Rifabutin 150 mg, bid
Gisbert J P et al. Aliment Pharmacol Ther 2012 ; 35 : 209 – 221.
For 10 – 12 days
Administered as rescue therapy without prior antibiogram
67. Rifabutin
Rifamycin-S derivative
• Indications Mycobacteria including MAC*
Third line treatment of H pylori
• Eradication 3rd line: 342 patients – 66% (55–77%)
4th / 5th line: 95 patients – 70% (60–79%)
• Resistance 2982 pts: 1.3% (95% CI: 0.9% to 1.7%)
• Adverse effects Myelotoxicity: Most significant – Rare
Recovered of leucopenia in few days
* MAC: Mycobacterium Avium-intracellulare Complex
Gisbert J P et al. Aliment Pharmacol Ther 2012 ; 35 : 209 – 221.
69. 2nd line*
Bismuth quadruple
PPI-Amoxicillin-Levofoxacin
PPI-Amoxicillin-Levofoxacin
Treatment regimen according to areas of Clari-R
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
* Regimen should not include antibiotics given previously
Region with low Clari-R
< 20%
Region with high Clari-R
> 20%
1st line
PPI-Amoxicillin-Clarithro
Bismuth quadruple
Bismuth quadruple
Sequential or Concomitant
3rd line Based on susceptibility testing only
70. Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
* Regimen should not include antibiotics given previously
Treatment in patients with penicillin allergy
Relatively common subgroup of patients
2nd line*
PPI – Clarithromycin – Levofoxacin
Region with low levofloxacin resistance
1st line
PPI-Clarithro-Metronidazole Bismuth quadruple
Region with low Clari-R
< 20%
Region with high Clari-R
> 20%
71. General recommendations for H. pylori treatment
• 1st line therapy Avoid CLA if given for any indication
Avoid LEV if given for any indication
Use 4 drugs : sequential, bismuth, hybrid
Use higher doses of drugs
Use 14 day duration
• 2nd line therapy Do not reuse same drugs
• 3rd line therapy Use culture-guided therapy if available
Rifabutin-based therapy as last resort
Graham DY & Fischbach L. Gut 2010 ; 59 : 1143 – 1153.
72. Helicobacter pylori infection
Discovery of H. pylori
Epidemiology of H. pylori
Indications for treatment
Diagnosis of infection
Treatment of infection
Prevention of gastric cancer
73. Risk factor for gastric cancer
• H. pylori Most consistent risk factor
Eradication reduces risk of cancer
• Genetic factors Cytokines: IL-1β, IL-8, IL-10, TNF-α
No recommended marker at present
• Environmental factors N-nitroso compounds
Salted foods, tobacco, alcohol
Subordinate to effect of HP infection
Protective effect of NSAID & aspirin
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
74. Gastric cancer pathways
Eradication of H pylori reduces risk of gastric cancer
But not eliminate cancer due to predetermined genetic pathways:
Hereditary diffuse gastric cancers & autoimmune gastritis
Talley NJ. Lancet 2008 ; 372 : 350 – 352.
75. Carcinogenicity of H. pylori
Atrophic corpus gastritis
H. pylori infection
Hypochlorhydria
Overgrowth of non-HP
organisms
Reduce nitrates to nitrites
& N-nitrosamines
Reduced/absent concentrations
of ascorbic acid
Ascorbic acid scavenges
carcinogenic N-nitrosamines
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
76. Prevention of gastric cancer
Identification of subjects with high risk of gastric cancer
• Non-invasive tests Validated serology for H. pylori
Low incidence + Markers of atrophy (pepsinogens)
PGI: chief cell
PGII: chief cell – pyloric glands
Low PGI or low PG1/PGII → atrophy
• Invasive test Gastroscopy & biopsies
High incidence OLGA staging system*
* OLGA: Operative Link for Gastritis Assessment
Dinis-Ribeiro M et al. Endoscopy 2012 ; 44 : 74 – 94.
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
77. OLGA staging system for gastritis
International group of gastroenterologists & pathologists
• Applies histology reporting format for chronic hepatitis
• Given number of portal tracts for staging of hepatitis
Well-defined biopsy protocol Antrum (3) – Corpus (2)
• Main lesion of cirrhosis risk Fibrosis
Main marker of gastric cancer Mucosal atrophy
• Staging by combining degree of atrophy & topography
• Assess risk of gastric cancer Stage 0 to stage 4
OLGA: Operative Link for Gastritis Assessment
Rugge M & Genta RM. Gastroenterology 2005 ; 129 : 1807 – 8 .
78. Gastric biopsy sampling protocol
A1 – A2
Greater & lesser curvatures of distal antrum
A3
Lesser curvature at incisura angularis
C1 – C2
Anterior & posterior walls of proximal corpus
At least five biopsies
Rugge M et al. Dig Liver Dis 2008 ; 40 : 650 – 658.
79. Normal & atrophic glandular units in stomach
Nl mucosecreting gland Non-metaplastic atrophy
Normal oxyntic gland Non-metaplastic atrophy Metaplastic atrophy
Pseudopyloric metaplasia
Metaplastic atrophy
Intestinal metaplasia
Ruggea M et al. Dig Liver Dis 2008 ; 40 : 650 – 658.
AntrumCorpus
80. OLGA staging system for gastritis
Combining degree of atrophy & location
• Atrophy No atrophy (0%) Score 0
Mild (1 – 30%) Score 1
Moderate (31 – 60%) Score 2
Severe (> 60%) Score 3
• Location Antral atrophy score (Aas) Mean A1 + A2 + A3
Corpus atrophy score (Cas) Mean C1 + C2
• OLGA Overall Aas & Cas Stage 0, 1, 2: low risk
Stage 3, 4: high risk
Rugge M et al. Dig Liver Dis 2008 ; 40 : 650 – 658.
81. OLGA staging system for gastritis
Ruggea M et al. Dig Liver Dis 2008 ; 40 : 650 – 658.
A
n
t
r
u
m
No atrophy
Score 0
Mild atrophy
Score 1
Moderate atrophy
Score 2
Severe atrophy
Score 3
Stage 0 Stage I Stage II Stage II
Stage I Stage I Stage II Stage III
Stage II Stage II Stage III Stage IV
Stage III Stage III Stage IV Stage IV
Atrophy score
Corpus
No atrophy
Score 0
Mild atrophy
Score 1
Moderate atroph
Score 2
Severe atrophy
Score 3
82. Assessment of elementary lesions
• H. pylori status Positive – Negative
Absent in PPI user & atrophic gastritis
• Inflammation Lympho-monocytic – Polymorphic
May suggest presence of HP
• Metaplasia Intestinal – Pseudo-pyloric
• Precancerous lesions IEN (formerly dysplasia)*
* IEN: Intra-Epithelial Neoplasia
Rugge M et al. Dig Liver Dis 2011 ; 43S : S373 – S384.
Information on likely etiology: H. pylori, autoimmune,..
83. Stage II gastritis
Rugge M et al. Dig Liver Dis 2011 ; 43S : S373 – S384.
Stages 0, I, and II are associated with DU more than GU
84. Stage III gastritis
Rugge M et al. Dig Liver Dis 2011 ; 43S : S373 – S384.
GU encountered more frequently than in OLGA stages 0 – I – II
85. Stage III gastritis
Corpus predominant atrophy should suggest an autoimmune etiology
Rugge M et al. Dig Liver Dis 2011 ; 43S : S373 – S384.
86. Stage IV gastritis
Pan-atrophic gastritis
Endoscopic surveillance in stage III–IV patients
Rugge M et al. Dig Liver Dis 2011 ; 43S : S373 – S384.
87. Eradicating epidemic gastric cancer has long been a dream
Now this dream can come true
Rugge M et al. Nat Rev Gastroenterol Hepatol 2012 ; 9 : 128 – 129.
Gram-negative bacterium with helical rod shape.Prominent flagellae facilitating penetration of thick mucous layer in the stomach.
Flagellum: اهداب
Koch's postulates (or Henle-Koch postulates) are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch (German physician & bacteriologist ) and Friedrich Loeffler in 1884 and refined and published by Koch in 1890. Koch applied the postulates to establish the etiology of anthrax and tuberculosis, but they have been generalized to other diseases.However, Koch abandoned the second part of the first postulate altogether when he discovered asymptomatic carriers of cholera[1] and, later, Typhoid Mary. Asymptomatic carriers are now known to be a common feature of many infectious diseases, especially viruses such as polio, herpes simplex, HIV and hepatitis C. As a specific example, all doctors and virologists agree that poliovirus causes paralysis in just a few infected subjects, and the success of the polio vaccine in preventing disease supports the conviction that the poliovirus is the causative agent.The third postulate specifies "should", not "must", because as Koch himself proved in regard to both tuberculosis and cholera, not all organisms exposed to an infectious agent will acquire the infection. This may be due to chance, to acquired immunity, or to genetic immunity. An example of genetic immunity: human immunodeficiency virus (HIV) seems to be normally unable to infect persons who carry the deletion CCR5 Δ32.
In spite of frequent variations of media, and temperatures of incubation, from these 34 specimens, however, spiral bacteria were notcultured, because incubation was limited to 48 hours.
A silver stain (Warthin Starry) of HP (black wiggly things) on gastric mucus-secreting epithelial cells (x1000). This picture is notorious because it is of Dr. Marshall's stomach biopsy taken 8 days after he drank a culture of H. pylori. The experiment was published in 1985 (Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. Attempt to fulfill Koch's postulates for pyloric Campylobacter. Med J Aust 1985; 142: 436-439).
Barry Marshall receiving his Nobel Prize from His Majesty the King Carl XVI Gustaf of Sweden at the Stockholm Concert Hall, 10 December 2005.
When the t(11,18) translocation is present, HP eradication is usually ineffective & these patients need adjunctive & alternative treatments.
H pylori-positive patients eradication treatment improves the bioavailability of thyroxine and l-dopa.
Serological test: serological tests are not all equivalent. Only validated IgG serology tests should be used owing to variability in the accuracy of different commercial tests.Validated IgG serology may be used in setting of recent use of antimicrobial* and antisecretory drugs, or ulcer bleeding, atrophy and gastric malignancies.Fecal antigen test:Not often used despite its high sensitivity and specificity before and after treatment.Should have a more prominent place, as it is inexpensive and noninvasive.PCR: Sensitive and specific – Not standardized.Finger-stick serology testVery poor and cannot be equated with ELISA serology
In special cases where a gastric ulcer or gastric MALT lymphoma has been diagnosed, follow-up is necessary with upper digestive endoscopy and then biopsy-based tests can be performed.On considère que la masse bactérienne revient à sa valeur initiale en un mois.Au cas où le malade ne pourrait arrêter son traitement antisécrétoire, la prise de pansements gastriques qui n’ont pas ces conséquences peut être envisagée.
On considère que la masse bactérienne revient à sa valeur initiale en un mois.Au cas où le malade ne pourrait arrêter son traitement antisécrétoire, la prise de pansements gastriques qui n’ont pas ces conséquences peut être envisagée.
Rapid urease tests. Another indirect test for Helicobacter pylori, the rapid urease test, is based on metabolism of urea by urease. In this test, a mucosal biopsy is inoculated into a well that contains urea and a pH-sensitive dye (phenol red). If urease is present in the biopsy, urea in the medium is converted to NH4+, which will raise the pH. In response to an elevation in pH, the pH sensitive dye causes the well to change colors. This figure is an example of a rapid urease test, the CLOtestTM (Delta West Limited, Bentley, Western Australia). In this test, presence of H. pylori in a mucosal biopsy will be evidenced by a color change from yellow to red.
Clinicians should prescribe therapies providing grade A resultsIf not obtainable, grade B therapies should be prescribedGrade F therapies should be avoided
Patients with NUD, pangastritis, diabetes, smokers, or those with a high bacterial load may be predicted to be at a higher risk of failure with the standard 7-day triple therapy.Compliance: Compliance to therapy plays a major role.12% of patients prematurely stopped the eradication therapy as a result of side effects.Gastric acid secretion:Small proportion of subjects shows a high basal acid output, despite normal values of the gastrin. In these hypersecretor subjects, who probably have a larger parietal cell mass, lower eradication rates have been reported.Genetic polymorphism of CYP 450:Subjects are subgrouped into poor, intermediate, and extensive metabolizers.Although some controversial data do exist, standard PPI doses seem to be insufficient in extensive metabolizers to achieve an adequate pH inhibition needed for antibiotic activity in gastric mucosa, with consequent lower eradication rates.Gastroduodenal disease:Several studies reported lower H. pylori cure rates in patients with NUD as compared with those with peptic ulcer disease (PUD).Infection with different less virulent HP strains: cagA negative; vacA s2 or m2 genotype) & slow-proliferating strains.Infection recurrence has also been found to be significantly higher in NUD as compared with PUD patients.Gastritis pattern:Patients with pangastritis achieve lower eradication rates as compared with those with antral gastritis. Obesity:BMI significantly affected the H. pylori eradication rate after a standard 7-day triple therapy.However, this phenomenon was not confirmed when a prolonged 14-day triple therapy regimen was used.Smoking: Ongoing smoking has been consistently reported tonegatively affect therapeutic success rate after 7-day triple therapies.Smoking did not seem to significantly reduce eradication rate when either 14-day triple therapy or 10-day sequential therapy was used.Primary resistance to antibiotics:Resistance to different antibiotics undeniably plays a major role, & prevalence of H. pylori resistance seems to be increasing worldwide.Clarithromycinhas been found to be the main factor hampering the efficacy of standard therapiesMetronidazoleresistance seems to exert a minor impact on the therapeutic outcome.Primary resistance toward levofloxacin, an antibiotic generally used in second-line therapy regimens, is also increasing worldwide.Bacterial load in the stomach:High values being associated with lower eradication rates.Coccoid forms of H. pyloriNot susceptible to antibiotics, & their presence may have clinical relevance, due potential reactivation of HP in its spiral form after therapy.cagA status:cagA-negative H. pylori seems to be less susceptible to antibiotics as compared with cagA positive strains (eradication rate 11% lower). vacA alleles status:Presence of vacA s1m1 allele increases bacterial susceptibility as compared with vacA s2m2 allele.duodenal ulcer promoting (dup) status:H. pylori virulence factor affecting therapy efficacy. presence of dupA gene was found to be independent predictor of therapy failure [OR: 3.71; 95% CI, 1.07-12.83] at multivariate analysis.Data need to be confirmed in a larger and prospective series.Certain H pylori virulence factors and certain host genetic polymorphisms are known to affect the risk of any specific individual developing H. pylori-associated disease. However, there is no evidence that strategies based on testing for these factors are useful for an individual patient.
Clarithromycin must bind to ribosomes in order to kill H pylori. Resistance is associated with failure to bind to ribosomes, such that resistance cannot be overcome by increasing the dose or duration.
It must be stated that there is a cross-resistance in each family of antibiotics because the same resistance mechanism occurs: resistanceto clarithromycin indicates resistance to all macrolides, resistance to levofloxacin indicates resistance to all fluoroquinolonesincluding moxifloxacin, for example. There is no cross-resistance between different families of antibiotics which have different resistance mechanisms.
Concept described by Bigger in 1944 Dormant bacteria that can survive until antibiotics stopped Treatment failure without development of resistance Feature of dual therapy with PPI & amoxicillin Extended-duration therapy Bacteria oscillate between nonreplicating & replicating states Local pH < 6 maintains bacteria in nonreplicative state Theoretical basis of high-dose dual PPI therapy
Tuberculosis is a potentially good source of information as both it and H. pylori infection require treatment withmultiple drugs for a long duration.
High-dose PPIs increase cure rates by around 6 – 10% in comparison with standard doses.Increasing dose of PPI from, for example, 20 mg omeprazole twice daily to 40 mg of esomeprazole or rabeprazole twice daily may increase cure rates by 8 – 12%.Extending duration of triple therapy from 7 to 10 – 14 days improves eradication success by approximately 5% and may be considered.
treatment success fails to reach even 80% in most studies in the southern and central European countries of France, Italy, Spain and Turkey, populations which, as the Maastricht III report noted, tend to have a high prevalence (~18.5%) of clarithromycin resistance.triple therapy with a PPi, amoxicillin and clarithromycin should be avoided.
Overall, mean eradication rate with sequential regimen is higher than 90%, a tendency toward lower efficacy with this regimen is observed in the more recent studies.Almost all the studies analyzing sequential therapy have been performed in Italy & data obtained from Italy might not be readily extrapolated to other populations.Limitations of sequential therapy:Low validation outside ItalySmall sample size: < 50 in some protocolsLow quality of studies: Jadad score ≥3 in 1/10 studies in MA1Therapy complexity: reduced compliance in clinical practiceUnsuitable for dual clarithromycin & nitroimidazole resistanceUnsuitable for penicillin allergy
We have observed that using a combination of both metronidazole and clarithromycinin quadruple regimens is very effective at eradicating strains of H pylori resistant to either clarithromycin or metronidazole. In fact, only a negligible reduction in efficacy was observed when concomitant quadruple regimens containing a PPI, amoxicillin, clarithromycin and metronidazole (a nitroimidazole), were given to patients with either nitromidazole- or clarithromycin-resistant H pylori.
Widespread acceptance of this regimen was not forthcoming, possibly related to the requirement for dosing three or preferably four times daily, the administration of a large number of pills, a lack of availability of bismuth in many areas, and perhaps most importantly, until recently, the absence of a pharmaceutical sponsor to assist in education and marketing of the regimen.Capsule containing bismuth subcitrate (140 mg), metronidazole (125 mg), and tetracycline (125 mg) is available and FDA approved. The dosing is three capsules four times daily plus a PPI twice daily.
Antibiotic combination should be chosen according to local H pylori antibiotic resistance patterns.
Antibiotic combination should be chosen according to local H pylori antibiotic resistance patterns.
In case of clarithromycin resistance, rate of success of clarithromycin-containing triple therapy is very low (10-30%).After a first failure, if an endoscopy is carried out, culture (and standard susceptibility testing) should be considered in all regions before giving a second-line treatment because the chance of having a resistant organism is high, in the range of 60 - 70% for clarithromycin.Metronidazole susceptibility testing lacks reproducibility and no molecular alternative exists.Increasing metronidazole dosage and treatment duration may partially overcome resistance.Accuracy of fluoroquinolone molecular testing is not as reliable as for clarithromycin.
We provide patients with information sheet that cautions against aged cheese, sausage including bologna, salami & pepperoni, lima beans, lentils, snow peas, soybeans, canned figs & raisins, beer, ale & wines, licorice, soy sauce, monamineoxidase inhibitors, phenylpropanolamine, ephedrine, phenylephrine.
H. pylori resistance to amoxicillin is extremely rare.Therefore, rifabutin (together with a PPI and amoxicillin) can be administered as a rescue treatment without the need for a prior antibiogram.The ideal length of treatment remains unclear, but 10- to 12-day regimens are generally recommended.
Antibiotic combination should be chosen according to local H pylori antibiotic resistance patterns.
Inflammation of the gastric mucosa leads to an increase in both PGI and PGII serum levels, usually with a more marked increase of PGIIand thus a decrease in the PGI/II ratio. With the development of atrophy and loss of specialized cells, both PGI and PGII may decrease, but PGI usually shows a more marked decrease than PGII, thus there is a further decline in the PGI/II ratio (see review by Kuipers EJ: “In through the out door: serology for atrophic gastritis,” Eur J GastroenterolHepatol 2003: 877–879). Thus, a low PGI level, a lowPGI/II ratio, or both, are good indicators of atrophic changes in the gastric mucosa.Subjects with severe gastric atrophy, in whom H pylori has disappeared and who are therefore serologically negative for H pylori, are at a particularly high risk.
both the oxyntic and the antral mucosa have to be “explored”and also considering the incisuraangularis “highly informative” for purpose of establishing earliest onset of atrophic–metaplastic transformation.
Patients on PPI, H. pylori may be difficult (or even impossible) to identify histologically at antral or corpus level, in which case coexisting inflammatory lesions (polymorphs and lymphoid infiltrate) may suggest the bacterium’s presence and a comment on the suspectedbacterial etiology (“suspicious for H. pylori infection”) should be added (whatever the stage of atrophy recorded).