Jump to content

Peptic ulcer disease

From Wikipedia, the free encyclopedia
(Redirected fromBleeding ulcer)

Peptic ulcer disease
Other namesPeptic ulcer, stomach ulcer, gastric ulcer, duodenal ulcer
Anendoscopic imageshowing deep gastric ulcer.
SpecialtyGastroenterology
General surgery
SymptomsHeartburn,upper abdominal pain,nausea,belching,vomiting,blood in the stool,weight loss,weight gain,bloating,loss of appetite,[1]yellowing of the skin and whites of the eyes,difficulty swallowing
ComplicationsBleeding,perforation,ulcer perforation,blockage of the stomach[2]
CausesHelicobacter pyloribacteria,non-steroidal anti-inflammatory drugs(NSAIDs),tobacco smoking,Crohn's disease[1][3]
Diagnostic methodBased on symptoms, confirmed byendoscopyorbarium swallow[1]
Differential diagnosisStomach cancer,coronary heart disease,inflammation of the stomach lining,gallbladder inflammation[1]
TreatmentMedications,[1]stopping NSAIDs, stopping smoking, stoppingalcohol consumption
MedicationProton pump inhibitor,H2 blocker,antibiotics[1][4]
Frequency87.4 million (2015)[5]
Deaths267,500 (2015)[6]

Peptic ulcer diseaseis a break in the innerlining of the stomach,the first part of thesmall intestine,or sometimes the loweresophagus.[1][7]An ulcer in the stomach is called agastric ulcer,while one in the first part of the intestines is aduodenal ulcer.[1]The most common symptoms of a duodenal ulcer are waking at night withupper abdominal pain,and upperabdominal painthat improves with eating.[1]With a gastric ulcer, the pain may worsen with eating.[8]The pain is often described as aburningor dull ache.[1]Other symptoms includebelching,vomiting, weight loss, orpoor appetite.[1]About a third of older people with peptic ulcers have no symptoms.[1]Complications may includebleeding,perforation,andblockage of the stomach.[2]Bleeding occurs in as many as 15% of cases.[2]

Common causes include infection withHelicobacter pyloriandnon-steroidal anti-inflammatory drugs(NSAIDs).[1]Other, less common causes includetobacco smoking,stress as a result of other serious health conditions,Behçet's disease,Zollinger–Ellison syndrome,Crohn's disease,andliver cirrhosis.[1][3]Older people are more sensitive to the ulcer-causing effects of NSAIDs.[1]The diagnosis is typically suspected due to the presenting symptoms with confirmation by eitherendoscopyorbarium swallow.[1]H. pylorican be diagnosed by testing the blood forantibodies,aurea breath test,testing the stool for signs of the bacteria, or abiopsyof the stomach.[1]Other conditions that produce similar symptoms includestomach cancer,coronary heart disease,andinflammation of the stomach liningorgallbladder inflammation.[1]

Dietdoes not play an important role in either causing or preventing ulcers.[9]Treatment includes stopping smoking, stopping use of NSAIDs, stoppingalcohol,and taking medications to decrease stomach acid.[1]The medication used to decrease acid is usually either aproton pump inhibitor(PPI) or anH2 blocker,with four weeks of treatment initially recommended.[1]Ulcers due toH. pyloriare treated with a combination of medications, such asamoxicillin,clarithromycin,and a PPI.[4]Antibiotic resistanceis increasing and thus treatment may not always be effective.[4]Bleeding ulcers may be treated byendoscopy,with open surgery typically only used in cases in which it is not successful.[2]

Peptic ulcers are present in around 4% of the population.[1]New ulcers were found in around 87.4 million people worldwide during 2015.[5]About 10% of people develop a peptic ulcer at some point in their life.[10]Peptic ulcers resulted in 267,500 deaths in 2015, down from 327,000 in 1990.[6][11]The first description of a perforated peptic ulcer was in 1670, in PrincessHenrietta of England.[2]H. pyloriwas first identified as causing peptic ulcers byBarry MarshallandRobin Warrenin the late 20th century,[4]a discovery for which they received theNobel Prizein 2005.[12]

Signs and symptoms

[edit]
Gastric ulcer
Duodenal ulcer A2 stage, acute duodenal mucosal lesion (ADML)

Signs and symptoms of a peptic ulcer can include one or more of the following:[13]

  • abdominal pain,classicallyepigastric,strongly correlated with mealtimes. In case of duodenal ulcers, the pain appears about three hours after taking a meal and wakes the person from sleep;
  • bloatingand abdominal fullness;
  • waterbrash(a rush of saliva after an episode of regurgitation to dilute the acid in esophagus, although this is more associated withgastroesophageal reflux disease);
  • nausea and copious vomiting;
  • loss of appetiteand weight loss, in gastric ulcer;
  • weight gain, in duodenal ulcer, as the pain is relieved by eating;
  • hematemesis(vomiting of blood); this can occur due to bleeding directly from a gastric ulcer or from damage to the esophagus from severe/continuing vomiting.
  • melena(tarry, foul-smelling feces due to presence ofoxidizediron fromhemoglobin);
  • rarely, an ulcer can lead to a gastric orduodenal perforation,which leads toacute peritonitisand extreme, stabbing pain,[14]and requires immediate surgery.

A history ofheartburnorgastroesophageal reflux disease(GERD) and use of certain medications can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer includeNSAIDs(non-steroidal anti-inflammatory drugs) that inhibitcyclooxygenaseand mostglucocorticoids(e.g.,dexamethasoneandprednisolone).[15]

In people over the age of 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation byesophagogastroduodenoscopy.[citation needed]

The timing of symptoms in relation to the meal may differentiate between gastric and duodenal ulcers. A gastric ulcer would giveepigastricpain during the meal, associated with nausea and vomiting, asgastric acidproduction is increased as food enters the stomach. Pain in duodenal ulcers would be aggravated by hunger and relieved by a meal and is associated with night pain.[16]

Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the person's age. Furthermore, typical ulcers tend to heal and recur, and as a result the pain may occur for few days and weeks and then wane or disappear.[17]Usually, children and theelderlydo not develop any symptoms unless complications have arisen.

A burning or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours commonly accompanies ulcers. This pain can be misinterpreted ashunger,indigestion,orheartburn.Pain is usually caused by the ulcer, but it may be aggravated by thestomach acidwhen it comes into contact with the ulcerated area. The pain caused by peptic ulcers can be felt anywhere from the navel up to thesternum,it may last from few minutes to several hours, and it may be worse when the stomach is empty. Also, sometimes the pain may flare at night, and it can commonly be temporarily relieved by eating foods that buffer stomach acid or by taking anti-acid medication.[18]However, peptic ulcer disease symptoms may be different for everyone.[19]

Complications

[edit]
  • Gastrointestinal bleedingis the most common complication. Sudden large bleeding can be life-threatening.[20][21]It is associated with 5% to 10% death rate.[16]
  • Perforation(a hole in thewall of the gastrointestinal tract) following a gastric ulcer often leads to catastrophic consequences if left untreated. Erosion of the gastrointestinal wall by the ulcer leads to spillage of the stomach or intestinal contents into the abdominal cavity, leading to an acute chemicalperitonitis.[22]The first sign is often sudden intense abdominal pain,[16]as seen inValentino's syndrome.Posterior gastric wall perforation may lead to bleeding due to the involvement of gastroduodenal artery that lies posterior to the first part of the duodenum.[23]The death rate in this case is 20%.[16]
  • Penetration is a form of perforation in which the hole leads to and the ulcer continues into adjacent organs such as theliverandpancreas.[17]
  • Gastric outlet obstruction(stenosis) is a narrowing of the pyloric canal by scarring and swelling of the gastric antrum and duodenum due to peptic ulcers. The person often presents with severe vomiting.[16]
  • Cancer is included in the differential diagnosis (elucidated bybiopsy),Helicobacter pylorias the etiological factor making it 3 to 6 times more likely to develop stomach cancer from the ulcer.[17]The risk for developing gastrointestinal cancer also appears to be slightly higher with gastric ulcers.[24]

Cause

[edit]

H. pylori

[edit]

Helicobacter pyloriis one of the major causative factors of peptic ulcer disease. It secretesureaseto create an alkaline environment, which is suitable for its survival. It expresses blood group antigen-binding adhesin (BabA) and outer inflammatory protein adhesin (OipA), which enables it to attach to the gastric epithelium. The bacterium also expresses virulence factors such asCagAandPicB,which cause stomach mucosal inflammation. The VacA gene encodes for vacuolating cytotoxin, but its mechanism of causing peptic ulcers is unclear. Such stomach mucosal inflammation can be associated withhyperchlorhydria(increased stomach acid secretion) orhypochlorhydria(reduced stomach acid secretion). Inflammatorycytokinesinhibit theparietal cellacid secretion.H. pylorialso secretes certain products that inhibithydrogen potassium ATPase;activatecalcitonin gene-related peptidesensory neurons, which increasessomatostatinsecretion to inhibit acid production by parietal cells; and inhibitgastrinsecretion. This reduction in acid production causes gastric ulcers.[16]On the other hand, increased acid production at thepyloric antrumis associated with duodenal ulcers in 10% to 15% ofH. pyloriinfection cases. In this case, somatostatin production is reduced and gastrin production is increased, leading to increasedhistaminesecretion from theenterochromaffincells, thus increasing acid production. An acidic environment at the antrum causesmetaplasiaof the duodenal cells, causing duodenal ulcers.[16]

Human immune response toward the bacteria also determines the emergence of peptic ulcer disease. The human IL1B gene encodes forInterleukin 1 beta,and other genes that encode fortumour necrosis factor(TNF) andLymphotoxin alphaalso play a role in gastric inflammation.[16]

NSAIDs

[edit]

Takingnonsteroidal anti-inflammatory drugs(NSAIDs) such asaspirin[25]can increase the risk of peptic ulcer disease by four times compared to non-users. The risk of getting a peptic ulcer is two times for aspirin users. Risk of bleeding increases if NSAIDs are combined withselective serotonin reuptake inhibitor(SSRI),corticosteroids,antimineralocorticoids,andanticoagulants.The gastric mucosa protects itself fromgastric acidwith a layer of mucus, the secretion of which is stimulated by certainprostaglandins.NSAIDs block the function ofcyclooxygenase1 (COX-1), which is essential for the production of these prostaglandins. Besides this, NSAIDs also inhibit stomach mucosa cells proliferation and mucosal blood flow, reducingbicarbonateand mucus secretion, which reduces the integrity of the mucosa. Another type of NSAIDs, called COX-2 selective anti-inflammatory drugs (such ascelecoxib), preferentially inhibitCOX-2,which is less essential in the gastric mucosa. This reduces the probability of getting peptic ulcers; however, it can still delay ulcer healing for those who already have a peptic ulcer.[16]Peptic ulcers caused by NSAIDs differ from those caused byH. pylorias the latter's appear as a consequence of inflammation of the mucosa (presence of neutrophil and submucosal edema), the former instead as a consequence of a direct damage of the NSAID molecule against COX enzymes, altering the hydrophobic state of the mucus, the permeability of the lining epithelium and mitochondrial machinery of the cell itself. In this way NSAID's ulcers tend to complicate faster and dig deeper in the tissue causing more complications, often asymptomatically until a great portion of the tissue is involved.[26][27]

Stress

[edit]

Physiological (not psychological)stressdue to serious health problems, such as those requiring treatment in an intensive care unit, is well described as a cause of peptic ulcers, which are also known asstress ulcers.[3]

While chronic life stress was once believed to be the main cause of ulcers, this is no longer the case.[28]It is, however, still occasionally believed to play a role.[28]This may be due to the well-documented effects of stress on gastric physiology, increasing the risk in those with other causes, such asH. pylorior NSAID use.[29]

Diet

[edit]

Dietaryfactors, such asspiceconsumption, were hypothesized to cause ulcers until the late 20th century, but have been shown to be of relatively minor importance.[30]Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, appear to have little effect.[31][32]Similarly, while studies have found that alcohol consumption increases risk when associated withH. pyloriinfection, it does not seem to independently increase risk. Even when coupled withH. pyloriinfection, the increase is modest in comparison to the primary risk factor.[33][34][nb 1]

Other

[edit]

Other causes of peptic ulcer disease include gastricischaemia,drugs, metabolic disturbances,cytomegalovirus(CMV), upper abdominal radiotherapy,Crohn's disease,andvasculitis.[16]Gastrinomas(Zollinger–Ellison syndrome), or rare gastrin-secreting tumors, also cause multiple and difficult-to-heal ulcers.[35]

It is still unclear whether smoking increases the risk of getting peptic ulcers.[16]

Diagnosis

[edit]
Endoscopic image of gastric ulcer, biopsy proven to begastric cancer.

The diagnosis is mainly established based on the characteristic symptoms. Stomach pain is the most common sign of a peptic ulcer.[13]

More specifically, peptic ulcers erode themuscularis mucosae,at minimum reaching to the level of the submucosa (contrast with erosions, which do not involve the muscularis mucosae).[36]

Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrastx-rays.The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such asweight loss,becausestomach cancercan cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduceacid.[17]

Anesophagogastroduodenoscopy(EGD), a form ofendoscopy,also known as agastroscopy,is carried out on people in whom a peptic ulcer is suspected. It is also the gold standard of diagnosis for peptic ulcer disease.[16]By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.

One of the reasons thatblood testsare not reliable for accurate peptic ulcer diagnosis on their own is their inability to differentiate between past exposure to the bacteria and current infection. Additionally, a false negative result is possible with a blood test if the person has recently been taking certain drugs, such asantibioticsorproton-pump inhibitors.[37]

The diagnosis ofHelicobacter pylorican be made by:

  • Urea breath test(noninvasive and does not require EGD);
  • Direct culture from an EGD biopsy specimen; this is difficult and can be expensive. Most labs are not set up to performH. pyloricultures;
  • Direct detection ofureaseactivity in a biopsy specimen byrapid urease test;[16]
  • Measurement ofantibodylevels in the blood (does not require EGD). It is still somewhat controversial whether a positive antibody without EGD is enough to warrant eradication therapy;
  • Stoolantigentest;[38]
  • Histological examination and staining of an EGD biopsy.

The breath test uses radioactivecarbonto detect H. pylori.[39]To perform this exam, the person is asked to drink a tasteless liquid that contains the carbon as part of the substance that the bacteria breaks down. After an hour, the person is asked to blow into a sealed bag. If the person is infected withH. pylori,the breath sample will contain radioactivecarbon dioxide.This test provides the advantage of being able to monitor the response to treatment used to kill the bacteria.

The possibility of other causes of ulcers, notablymalignancy(gastric cancer), needs to be kept in mind. This is especially true in ulcers of thegreater curvature of the stomach;most are also a consequence of chronicH. pyloriinfection.

If a peptic ulcer perforates, air will leak from inside the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to "free gas" within the peritoneal cavity. If the person stands, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease.

Classification

[edit]
  1. Esophagus
  2. Stomach
  3. Ulcers
  4. Duodenum
  5. Mucosa
  6. Submucosa
  7. Muscle

Peptic ulcers are a form ofacid–peptic disorder.Peptic ulcers can be classified according to their location and other factors.

By location

[edit]

Modified Johnson

[edit]
  • TypeI:Ulcer along the body of the stomach, most often along the lesser curve at incisura angularis along the locus minoris resistantiae. Not associated with acid hypersecretion.
  • TypeII:Ulcer in the body in combination with duodenal ulcers. Associated with acid oversecretion.
  • TypeIII:In the pyloric channel within 3 cm of pylorus. Associated with acid oversecretion.
  • TypeIV:Proximal gastroesophageal ulcer.
  • TypeV:Can occur throughout the stomach. Associated with the chronic use of NSAIDs (such asibuprofen).

Macroscopic appearance

[edit]
A benign gastric ulcer (from the antrum) of agastrectomyspecimen.

Gastric ulcers are most often localized on the lesser curvature of the stomach. The ulcer is a round to oval parietal defect ( "hole" ), 2–4 cm diameter, with a smooth base and perpendicular borders. These borders are not elevated or irregular in the acute form of peptic ulcer, and regular but with elevated borders and inflammatory surrounding in the chronic form. In the ulcerative form of gastric cancer, the borders are irregular. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.[citation needed]

Microscopic appearance

[edit]
Micrograph showing erosive gastric ulcer. (H&E stain)

A gastric peptic ulcer is a mucosal perforation that penetrates themuscularis mucosaeand lamina propria, usually produced by acid-pepsin aggression. Ulcer margins are perpendicular and present chronic gastritis. During the active phase, the base of the ulcer shows four zones: fibrinoid necrosis, inflammatory exudate, granulation tissue and fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.[40]

Differential diagnosis

[edit]

Conditions that may appear similar include:

Prevention

[edit]

Prevention of peptic ulcer disease for those who are taking NSAIDs (with low cardiovascular risk) can be achieved by adding aproton pump inhibitor(PPI), anH2 antagonist,ormisoprostol.[16]NSAIDs of the COX-2 inhibitors type may reduce the rate of ulcers when compared to non-selective NSAIDs.[16]PPI is the most popular agent in peptic ulcer prevention.[16]However, there is no evidence that H2 antagonists can prevent stomach bleeding for those taking NSAIDs.[16]Although misoprostol is effective in preventing peptic ulcer, its properties of promoting abortion and causing gastrointestinal distress limit its use.[16]For those with high cardiovascular risk, naproxen with PPI can be a useful choice.[16]Otherwise, low-dose aspirin, celecoxib, and PPI can also be used.[16]

Management

[edit]
Peptic ulcer treatment: pharmacology of drugs

Eradication therapy

[edit]

Once the diagnosis ofH. pyloriis confirmed, the first-line treatment would be a triple regimen in whichpantoprazoleandclarithromycinare combined with eitheramoxicillinormetronidazole.This treatment regimen can be given for 7–14 days. However, its effectiveness in eradicatingH. pylorihas been reducing from 90% to 70%. However, the rate of eradication can be increased by doubling the dosage of pantoprazole or increasing the duration of treatment to 14 days. Quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole) can also be used. The quadruple therapy can achieve an eradication rate of 90%. If the clarithromycin resistance rate is higher than 15% in an area, the usage of clarithromycin should be abandoned. Instead,bismuth-containing quadruple therapy can be used (pantoprazole, bismuth citrate,tetracycline,and metronidazole) for 14 days. The bismuth therapy can also achieve an eradication rate of 90% and can be used as second-line therapy when the first-line triple-regimen therapy has failed.

NSAIDs-induced ulcers

[edit]

NSAID-associated ulcers heal in six to eight weeks provided the NSAIDs are withdrawn with the introduction ofproton pump inhibitors(PPI).[16]

Bleeding

[edit]

For those with bleeding peptic ulcers,fluid replacementwithcrystalloidsis sometimes given to maintain volume in the blood vessels. Maintaining haemoglobin at greater than 7 g/dL (70 g/L) through restrictive blood transfusion has been associated with reduced rate of death.Glasgow-Blatchford scoreis used to determine whether a person should be treated inside a hospital or as an outpatient.IntravenousPPIs can suppress stomach bleeding more quickly than oral ones. A neutral stomach pH is required to keep platelets in place and prevent clot lysis.Tranexamic acidandantifibrinolyticagents are not useful in treating peptic ulcer disease.[16]

Early endoscopic therapy can help to stop bleeding by usingcautery,endoclip,orepinephrineinjection. Treatment is indicated if there is active bleeding in the stomach, visible vessels, or an adherent clot. Endoscopy is also helpful in identifying people who are suitable for hospital discharge.Prokinetic agentssuch aserythromycinandmetoclopramidecan be given before endoscopy to improve endoscopic view. Either high- or low-dose PPIs are equally effective in reducing bleeding after endoscopy. High-dose intravenous PPI is defined as a bolus dose of 80 mg followed by an infusion of 8 mg per hour for 72 hours—in other words, the continuous infusion of PPI of greater than 192 mg per day. Intravenous PPI can be changed to oral once there is no high risk of rebleeding from peptic ulcer.[16]

For those withhypovolemic shockand ulcer size of greater than 2 cm, there is a high chance that the endoscopic treatment would fail. Therefore, surgery and angiographic embolism are reserved for these complicated cases. However, there is a higher rate of complication for those who underwent surgery to patch the stomach bleeding site when compared to repeated endoscopy.Angiographic embolisationhas a higher rebleeding rate but a similar rate of death to surgery.[16]

Anticoagulants

[edit]

According to expert opinion, for those who are already on anticoagulants, theinternational normalized ratio(INR) should be kept at 1.5. For aspirin users who required endoscopic treatment for bleeding peptic ulcer, there is two times increased risk of rebleeding but with ten times reduced risk of death at eight weeks following the resumption of aspirin. For those who were on double antiplatelet agents for indwelling stent in blood vessels, both antiplatelet agents should not be stopped because there is a high risk of stent thrombosis. For those who were underwarfarintreatment,fresh frozen plasma(FFP), vitamin K, prothrombin complex concentrates, or recombinant factor VIIa can be given to reverse the effect of warfarin. High doses of vitamin K should be avoided to reduce the time for rewarfarinisation once the stomach bleeding has stopped. Prothrombin complex concentrates are preferred for severe bleeding. Recombinant factor VIIa is reserved for life-threatening bleeding because of its high risk of thromboembolism.[16]Direct oral anticoagulants(DOAC) are recommended instead of warfarin as they are more effective in preventing thromboembolism. In case of bleeding caused by DOAC,activated charcoalwithin four hours is the antidote of choice.

Epidemiology

[edit]
Deaths from peptic ulcer disease per million persons in 2012
0-7
8-11
12-16
17-19
20-25
26-32
33-40
41-53
54-72
73-132
Disability-adjusted life yearfor peptic ulcer disease per 100,000 inhabitants in 2004.[41]
no data
less than 20
20–40
40–60
60–80
80–100
100–120
120–140
140–160
160–180
180–200
200–220
more than 220

The lifetime risk for developing a peptic ulcer is approximately 5% to 10%[10][16]with the rate of 0.1% to 0.3% per year.[16]Peptic ulcers resulted in 301,000 deaths in 2013, down from 327,000 in 1990.[11]

In Western countries, the percentage of people withH. pyloriinfections roughly matches age (i.e., 20% at age 20, 30% at age 30, 80% at age 80, etc.). Prevalence is higher in third world countries, where it is estimated at 70% of the population, whereas developed countries show a maximum of a 40% ratio. Overall,H. pyloriinfections show a worldwide decrease, more so in developed countries. Transmission occurs via food, contaminated groundwater, or human saliva (such as from kissing or sharing food utensils).[42]

Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century when epidemiological trends started to point to an impressive fall in its incidence. The reason that the rates of peptic ulcer disease decreased is thought to be the development of new effective medication and acid suppressants and the rational use ofnonsteroidal anti-inflammatory drugs(NSAIDs).[16]

History

[edit]
See also:Timeline of peptic ulcer disease and Helicobacter pylori

John Lykoudis,ageneral practitionerinGreece,treated people for peptic ulcer disease withantibioticsbeginning in 1958, long before it was commonly recognized that bacteria were a dominant cause for the disease.[43]

Helicobacter pyloriwas identified in 1982 by twoAustralianscientists,Robin WarrenandBarry J. Marshall,as a causative factor for ulcers.[44]In their original paper, Warren and Marshall contended that most gastric ulcers and gastritis were caused by colonization with this bacterium, not bystressorspicy food,as had been assumed before.[45]

TheH. pylorihypothesis was still poorly received,[46]so in an act ofself-experimentationMarshall drank aPetri dishcontaining a culture of organisms extracted from a person with an ulcer and five days later developed gastritis. His symptoms disappeared after two weeks, but he took antibiotics to kill the remaining bacteria at the urging of his wife, sincehalitosisis one of the symptoms of infection.[47]This experiment was published in 1984 in theAustralian Medical Journaland is among the most cited articles from the journal.

In 1997, theCenters for Disease Control and Prevention,with other government agencies, academic institutions, and industry, launched a national education campaign to inform health care providers and consumers about the link betweenH. pyloriand ulcers. This campaign reinforced the news that ulcers are a curable infection and that health can be greatly improved and money saved by disseminating information aboutH. pylori.[48]

In 2005, theKarolinska Institute in Stockholmawarded theNobel Prize in Physiology or Medicineto Marshall and his long-time collaborator Warren "for their discovery of the bacteriumHelicobacter pyloriand its role ingastritisand peptic ulcer disease. "Marshall continues research related toH. pyloriand runs a molecular biology lab atUWAin Perth, Western Australia.

A 1998 New England Medical Journal study found thatmastic gum,a tree resin extract, actively eliminated theH. pyloribacteria.[49]However, multiple subsequent studies (in mice and in vivo) have found no effect of using mastic gum on reducingH. pylorilevels.[50][51]

Notes

[edit]
  1. ^Sonnenberg in his study cautiously concludes that, among other potential factors that were found to correlate to ulcer healing, "moderate alcohol intake might [also] favor ulcer healing." (p. 1066)

References

[edit]
  1. ^abcdefghijklmnopqrstuNajm WI (September 2011). "Peptic ulcer disease".Primary Care.38(3): 383–94, vii.doi:10.1016/j.pop.2011.05.001.PMID21872087.
  2. ^abcdeMilosavljevic T, Kostić-Milosavljević M, Jovanović I, Krstić M (2011). "Complications of peptic ulcer disease".Digestive Diseases.29(5): 491–3.doi:10.1159/000331517.PMID22095016.S2CID25464311.
  3. ^abcSteinberg KP (June 2002). "Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit".Critical Care Medicine.30(6 Suppl): S362–4.doi:10.1097/00003246-200206001-00005.PMID12072662.
  4. ^abcdWang AY, Peura DA (October 2011). "The prevalence and incidence of Helicobacter pylori-associated peptic ulcer disease and upper gastrointestinal bleeding throughout the world".Gastrointestinal Endoscopy Clinics of North America.21(4): 613–35.doi:10.1016/j.giec.2011.07.011.PMID21944414.
  5. ^ab"Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015".Lancet.388(10053): 1545–1602. October 2016.doi:10.1016/S0140-6736(16)31678-6.PMC5055577.PMID27733282.
  6. ^abWang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, Casey DC, Charlson FJ, Chen AZ, Coates MM, Coggeshall M, Dandona L, Dicker DJ, Erskine HE, Ferrari AJ, Fitzmaurice C, Foreman K, Forouzanfar MH, Fraser MS, Fullman N, Gething PW, Goldberg EM, Graetz N, Haagsma JA, Hay SI, Huynh C, Johnson CO, Kassebaum NJ, Kinfu Y, Kulikoff XR (October 2016)."Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015".Lancet.388(10053): 1459–1544.doi:10.1016/s0140-6736(16)31012-1.PMC5388903.PMID27733281.
  7. ^"Definition and Facts for Peptic Ulcer Disease".National Institute of Diabetes and Digestive and Kidney Diseases.Archived fromthe originalon 2 April 2015.Retrieved28 February2015.
  8. ^Rao SD (2014).Clinical Manual of Surgery.Elsevier Health Sciences. p. 526.ISBN9788131238714.
  9. ^"Eating, Diet, and Nutrition for Peptic Ulcer Disease".National Institute of Diabetes and Digestive and Kidney Diseases.Archived fromthe originalon 20 March 2015.Retrieved28 February2015.
  10. ^abSnowden FM (October 2008)."Emerging and reemerging diseases: a historical perspective".Immunological Reviews.225(1): 9–26.doi:10.1111/j.1600-065X.2008.00677.x.PMC7165909.PMID18837773.
  11. ^ab"Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013".Lancet.385(9963): 117–71. January 2015.doi:10.1016/S0140-6736(14)61682-2.PMC4340604.PMID25530442.
  12. ^"The Nobel Prize in Physiology or Medicine 2005".nobelprize.org.Nobel Media AB.Archivedfrom the original on 12 May 2015.Retrieved3 June2015.
  13. ^ab"Symptoms & Causes of Peptic Ulcers (Stomach or Duodenal Ulcers) - NIDDK".National Institute of Diabetes and Digestive and Kidney Diseases.Retrieved7 June2024.
  14. ^Bhat S (2013).SRB's Manual of Surgery.JP Medical. p. 364.ISBN9789350259443.
  15. ^"Treatment for Peptic Ulcers (Stomach or Duodenal Ulcers) - NIDDK".National Institute of Diabetes and Digestive and Kidney Diseases.Retrieved7 June2024.
  16. ^abcdefghijklmnopqrstuvwxyzaaabLanas A, Chan FK (August 2017). "Peptic ulcer disease".Lancet.390(10094): 613–624.doi:10.1016/S0140-6736(16)32404-7.PMID28242110.S2CID4547048.
  17. ^abcd"Peptic Ulcer".Home Health Handbook for Patients & Caregivers.Merck Manuals. October 2006.Archivedfrom the original on 28 December 2011.
  18. ^"Peptic ulcer".Archivedfrom the original on 14 February 2012.Retrieved18 June2010.
  19. ^"Ulcer Disease Facts and Myths".Archived fromthe originalon 5 June 2010.Retrieved18 June2010.
  20. ^Cullen DJ, Hawkey GM, Greenwood DC, Humphreys H, Shepherd V, Logan RF, Hawkey CJ (October 1997)."Peptic ulcer bleeding in the elderly: relative roles ofHelicobacter pyloriand non-steroidal anti-inflammatory drugs ".Gut.41(4): 459–62.doi:10.1136/gut.41.4.459.PMC1891536.PMID9391242.
  21. ^Blackford, John W.,Williams, Robert H.(1940). "Fatal Hemorrhage from Peptic Ulcer: One Hundred and Sixteen Cases Collected from Vital Statistics of Seattle During the Years 1935-1939 Inclusive".Journal of the American Medical Association.115(21): 1774–1779.doi:10.1001/jama.1940.02810470018005.
  22. ^Gossman W, Tuma F, Kamel BG, Cassaro S (2019). "Gastric Perforation".StatPearls.StatPearls Publishing.PMID30137838.
  23. ^Weledji EP (9 November 2020)."An Overview of Gastroduodenal Perforation".Frontiers in Surgery.7:573901.doi:10.3389/fsurg.2020.573901.ISSN2296-875X.PMC7680839.PMID33240923.
  24. ^Søgaard KK, Farkas DK, Pedersen L, Lund JL, Thomsen RW, Sørensen HT (2016)."Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers".Cancer Medicine.5(6): 1341–1351.doi:10.1002/cam4.680.PMC4924392.PMID26923747.
  25. ^Chan FK, Graham DY (15 May 2004)."Review article: prevention of non-steroidal anti-inflammatory drug gastrointestinal complications--review and recommendations based on risk assessment".Aliment Pharmacol Ther.19(10): 1051–61.doi:10.1111/j.1365-2036.2004.01935.x.PMID15142194.S2CID24654342.Retrieved27 February2022.
  26. ^"NSAIDs: When To Use Them and for How Long".Cleveland Clinic.Retrieved7 June2024.
  27. ^Ghlichloo I, Gerriets V (2024),"Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)",StatPearls,Treasure Island (FL): StatPearls Publishing,PMID31613522,retrieved7 June2024
  28. ^abFink G (February 2011). "Stress controversies: post-traumatic stress disorder, hippocampal volume, gastroduodenal ulceration*".Journal of Neuroendocrinology.23(2): 107–17.doi:10.1111/j.1365-2826.2010.02089.x.PMID20973838.S2CID30231594.
  29. ^Yeomans ND (January 2011)."The ulcer sleuths: The search for the cause of peptic ulcers".Journal of Gastroenterology and Hepatology.26(Suppl 1): 35–41.doi:10.1111/j.1440-1746.2010.06537.x.PMID21199512.S2CID42592868.
  30. ^For nearly 100 years, scientists and doctors thought that ulcers were caused by stress, spicy food, and alcohol. Treatment involvedbed restand a bland diet. Later, researchers added stomach acid to the list of causes and began treating ulcers with antacids.National Digestive Diseases Information ClearinghouseArchived5 July 2006 at theWayback Machine
  31. ^Ryan-Harshman M, Aldoori W (May 2004)."How diet and lifestyle affect duodenal ulcers. Review of the evidence".Canadian Family Physician.50:727–32.PMC2214597.PMID15171675.
  32. ^Rubin R, Strayer DS, Rubin E (1 February 2011).Rubin's pathology: clinicopathologic foundations of medicine(Sixth ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 623.ISBN978-1-60547-968-2.
  33. ^Salih BA, Abasiyanik MF, Bayyurt N, Sander E (June 2007)."H pylori infection and other risk factors associated with peptic ulcers in Turkish patients: a retrospective study".World Journal of Gastroenterology.13(23): 3245–8.doi:10.3748/wjg.v13.i23.3245.PMC4436612.PMID17589905.
  34. ^Sonnenberg A, Müller-Lissner SA, Vogel E, Schmid P, Gonvers JJ, Peter P, Strohmeyer G, Blum AL (December 1981)."Predictors of duodenal ulcer healing and relapse".Gastroenterology.81(6): 1061–7.doi:10.1016/S0016-5085(81)80012-1.PMID7026344.
  35. ^Feliberti E, Hughes MS, Perry RR, Vinik A, Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A, Wilson DP (28 November 2013). "Gastrinoma Zollinger-Ellison-Syndrome".Endotext.PMID25905301.
  36. ^"Peptic Ulcer Disease".Archivedfrom the original on 13 January 2016.Retrieved17 January2016.
  37. ^"Peptic ulcer".Archivedfrom the original on 9 February 2010.Retrieved18 June2010.
  38. ^Stenström B, Mendis A, Marshall B (August 2008). "Helicobacter pylori--the latest in diagnosis and treatment".Australian Family Physician.37(8): 608–12.PMID18704207.
  39. ^"Tests and diagnosis".Archivedfrom the original on 9 February 2010.Retrieved18 June2010.
  40. ^"ATLAS OF PATHOLOGY".Archivedfrom the original on 9 February 2009.Retrieved26 August2007.
  41. ^"WHO Disease and injury country estimates".World Health Organization.2009.Archivedfrom the original on 11 November 2009.Retrieved11 November2009.
  42. ^Brown LM (2000)."Helicobacter pylori: epidemiology and routes of transmission".Epidemiologic Reviews.22(2): 283–97.doi:10.1093/oxfordjournals.epirev.a018040.PMID11218379.
  43. ^Rigas B, Papavasassiliou ED (22 May 2002)."Ch. 7 John Lykoudis. The general practitioner in Greece who in 1958 discovered the etiology of, and a treatment for, peptic ulcer disease.".In Marshall BJ (ed.).Helicobacter pioneers: firsthand accounts from the scientists who discovered helicobacters, 1892–1982.John Wiley & Sons. pp. 74–88.ISBN978-0-86793-035-1.Archivedfrom the original on 21 May 2016.
  44. ^Warren JR, Marshall B (June 1983). "Unidentified curved bacilli on gastric epithelium in active chronic gastritis".Lancet.1(8336): 1273–5.doi:10.1016/S0140-6736(83)92719-8.PMID6134060.S2CID1641856.
  45. ^Marshall BJ, Warren JR (June 1984). "Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration".Lancet.1(8390): 1311–5.doi:10.1016/S0140-6736(84)91816-6.PMID6145023.S2CID10066001.
  46. ^Schulz K(9 September 2010)."Stress Doesn't Cause Ulcers! Or, How To Win a Nobel Prize in One Easy Lesson: Barry Marshall on Being... Right".The Wrong Stuff.Slate.Archivedfrom the original on 5 August 2011.Retrieved17 July2011.
  47. ^Van Der Weyden MB, Armstrong RM, Gregory AT (2005)."The 2005 Nobel Prize in physiology or medicine".The Medical Journal of Australia.183(11–12): 612–4.doi:10.5694/j.1326-5377.2005.tb00052.x.PMID16336147.S2CID45487832.Archivedfrom the original on 27 June 2009.
  48. ^"Ulcer, Diagnosis and Treatment - CDC Bacterial, Mycotic Diseases".Cdc.gov.Archivedfrom the original on 3 December 2013.Retrieved27 February2014.
  49. ^Huwez FU, Thirlwell D, Cockayne A, Ala'Aldeen DA (December 1998)."Mastic gum kills Helicobacter pylori".The New England Journal of Medicine.339(26): 1946.doi:10.1056/NEJM199812243392618.PMID9874617.Archivedfrom the original on 15 September 2008.See alsotheir corrections in the next volumeArchived5 October 2008 at theWayback Machine.
  50. ^Loughlin MF, Ala'Aldeen DA, Jenks PJ (February 2003)."Monotherapy with mastic does not eradicate Helicobacter pylori infection from mice".The Journal of Antimicrobial Chemotherapy.51(2): 367–71.doi:10.1093/jac/dkg057.PMID12562704.
  51. ^Bebb JR, Bailey-Flitter N, Ala'Aldeen D, Atherton JC (September 2003)."Mastic gum has no effect on Helicobacter pylori load in vivo".The Journal of Antimicrobial Chemotherapy.52(3): 522–3.doi:10.1093/jac/dkg366.PMID12888582.
[edit]
Wikimedia Commons has media related toPeptic ulcers.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Peptic_ulcer_disease&oldid=1245404423"