diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate. more specifically, peptic ulcers erode the muscularis mucosae, at minimum reaching to the level of the submucosa (contrast with erosions, which do not involve the muscularis mucosae). confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast x-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 as weight loss, because stomach cancer can 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 overproduce acid. an esophagogastroduodenoscopy (egd), a form of endoscopy, also known as a gastroscopy, is carried out on people in whom a peptic ulcer is suspected. it is also the gold standard of diagnosis for peptic ulcer disease. 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 that blood tests are 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 as antibiotics or proton-pump inhibitors. the diagnosis of helicobacter pylori can 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 perform h. pylori cultures; direct detection of urease activity in a biopsy specimen by rapid urease test; measurement of antibody levels in the blood (does not require egd). it is still somewhat controversial whether a positive antibody without egd is enough to warrant eradication therapy; stool antigen test; histological examination and staining of an egd biopsy. the breath test uses radioactive carbon to detect h. pylori. 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 with h. pylori, the breath sample will contain radioactive carbon 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, notably malignancy (gastric cancer), needs to be kept in mind. this is especially true in ulcers of the greater (large) curvature of the stomach; most are also a consequence of chronic h. pylori infection. 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 esophagusstomachulcersduodenummucosasubmucosamuscle peptic ulcers are a form of acid–peptic disorder. peptic ulcers can be classified according to their location and other factors. by location duodenum (called duodenal ulcer) esophagus (called esophageal ulcer) stomach (called gastric ulcer) meckel's diverticulum (called meckel's diverticulum ulcer; is very tender with palpation) modified johnson type i: 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. type ii: ulcer in the body in combination with duodenal ulcers. associated with acid oversecretion. type iii: in the pyloric channel within 3 cm of pylorus. associated with acid oversecretion. type iv: proximal gastroesophageal ulcer. type v: can occur throughout the stomach. associated with the chronic use of nsaids (such as ibuprofen). macroscopic appearance a benign gastric ulcer (from the antrum) of a gastrectomy specimen. 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. microscopic appearance micrograph showing erosive gastric ulcer. (h&e stain) a gastric peptic ulcer is a mucosal perforation that penetrates the muscularis mucosae and 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 4 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. differential diagnosis conditions that may appear similar include: gastritis stomach cancer gastroesophageal reflux disease pancreatitis hepatic congestion cholecystitis biliary colic inferior myocardial infarction referred pain (pleurisy, pericarditis) superior mesenteric artery syndrome prevention prevention of peptic ulcer disease for those who are taking nsaids (with low cardiovascular risk) can be achieved by adding a proton pump inhibitor (ppi), an h2 antagonist, or misoprostol. nsaids of the cox-2 inhibitors type may reduce the rate of ulcers when compared to non-selective nsaids. ppi is the most popular agent in peptic ulcer prevention. however, there is no evidence that h2 antagonists can prevent stomach bleeding for those taking nsaids. although misoprostol is effective in preventing peptic ulcer, its properties of promoting abortion and causing gastrointestinal distress limit its use. for those with high cardiovascular risk, naproxen with ppi can be a useful choice. otherwise, low-dose aspirin, celecoxib, and ppi can also be used. management peptic ulcer treatment: pharmacology of drugs eradication therapy once the diagnosis of h. pylori is confirmed, the first-line treatment would be a triple regimen in which pantoprazole and clarithromycin are combined with either amoxicillin or metronidazole. this treatment regimen can be given for 7–14 days. however, its effectiveness in eradicating h. pylori has 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 nsaid-associated ulcers heal in 6 to 8 weeks provided the nsaids are withdrawn with the introduction of proton pump inhibitors (ppi). bleeding for those with bleeding peptic ulcers, fluid replacement with crystalloids is 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 score is used to determine whether a person should be treated inside a hospital or as an outpatient. intravenous ppis 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 acid and antifibrinolytic agents are not useful in treating peptic ulcer disease. early endoscopic therapy can help to stop bleeding by using cautery, endoclip, or epinephrine injection. 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 agents such as erythromycin and metoclopramide can 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. for those with hypovolemic shock and 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 embolisation has a higher rebleeding rate but a similar rate of death to surgery. anticoagulants according to expert opinion, for those who are already on anticoagulants, the international 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 10 times reduced risk of death at 8 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 under warfarin treatment, 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. 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 charcoal within 4 hours is the antidote of choice. epidemiology 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 year for peptic ulcer disease per 100,000 inhabitants in 2004. 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% with the rate of 0.1% to 0.3% per year. peptic ulcers resulted in 301,000 deaths in 2013, down from 327,000 in 1990. in western countries, the percentage of people with h. pylori infections 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. pylori infections 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). 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 of nonsteroidal anti-inflammatory drugs (nsaids). history