Duodenal ulcer

Duodenal ulcer is an open sore or an ulcer that develops in the lining of your duodenum, the first part of your small intestine ¹, ², ³. Your duodenum helps to further digest food coming from your stomach. It absorbs nutrients (vitamins, minerals, carbohydrates, fats, proteins) and water from food so they can be used by your body. Your duodenum has a protective lining that keeps out germs like bacteria, viruses and parasites. Your duodenum also shields against damage from your stomach’s highly acidic digestive juices. Duodenal ulcer is a type of peptic ulcer, along with stomach ulcer. If you have either of these, you have what doctors called ‘peptic ulcer disease‘. These ulcers can cause pain in your upper abdomen, just below your breastbone. The most common causes of duodenal ulcers are infection with the Helicobacter pylori (H. pylori) bacteria and long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen and aspirin ⁴, ⁵, ⁶. If left untreated, duodenal ulcers can lead to complications like bleeding, perforation (a hole in the duodenum wall), or obstruction.

Duodenal ulcer symptoms may include:

• Upper abdominal pain (abdominal pain 2 to 3 hours after eating a meal on an empty stomach or epigastric abdominal pain that improved after eating).
• Bloating (tight, full or painful feeling in your upper abdomen after eating).
• Nausea and vomiting.
• Diarrhea.
• Fatigue.
• Gas.
• Loss of appetite.
• Weight loss.

Bleeding in your digestive tract is sometimes a sign of severe duodenal ulcer. Signs include:

• Blood in your vomit (may look like coffee grounds).
• Blood in your poop (may look dark-colored or tarry).
• You have a sharp pain in your stomach that doesn’t go away.
• Feeling dizzy or fainting.

You should see a doctor if you notice these signs, which may mean you have duodenal ulcer or another digestive system condition that needs treatment.

Duodenal ulcer diagnosis typically involves an upper endoscopy, a procedure where a thin, flexible tube with a camera is inserted into the digestive tract to visualize the lining.

Duodenal ulcer treatment depends on the specific cause and usually involves medication to reduce stomach acid like proton pump inhibitors (PPIs) and histamine 2 blockers (H2 blockers) and antibiotics to treat H. pylori infection if present. Once treated, duodenal ulcer usually get better within a few weeks.

Medicines used to treat duodenal ulcer include:

• Antibiotics to kill Helicobacter pylori. For H. pylori in your digestive tract, your doctor may recommend a combination of antibiotics to kill the Helicobacter pylori bacteria. Be sure to take the full antibiotic prescription, usually for 7 to 14 days. You also may take a medicine to block acid production. Once treated, your doctor will retest you for H. pylori to be sure it has been destroyed.
• Medicines that block acid production and promote healing. Medicines called proton pump inhibitors (PPIs) help reduce acid. They do this by blocking the action of the parts of cells that produce acid. You may get a prescription for proton pump inhibitors (PPIs) or you can buy them without a prescription. Long-term use of proton pump inhibitors (PPIs), particularly at high doses, may increase your risk of hip, wrist and spine fractures. Ask your doctor whether a calcium supplement may reduce this risk.
• Medicines to reduce acid production. Acid blockers, also called histamine blockers or H2 blockers, reduce the amount of acid released into your digestive tract. Reducing acid relieves duodenitis pain and encourages healing. You may get a prescription for an acid blocker, or you can buy one without a prescription.
• Medicines that neutralize stomach acid. Your doctor may include an antacid in your treatment. Antacids neutralize existing stomach acid and can provide rapid pain relief. These help with immediate symptom relief but are generally not used as a primary treatment. Side effects of antacids can include constipation or diarrhea, depending on the main ingredients. Proton pump inhibitors and acid blockers are more effective and have fewer side effects.

How can I lower my risk of duodenal ulcer?

You can follow good hygiene practices to reduce your risk of H.pylori infection. Make sure you live a healthy lifestyle.

• Wash your hands. Proper handwashing techniques done at the right times can keep you from getting sick. Wash your hands when you’re preparing food and before eating. Wash your hands each time you finish using the toilet.
• Don’t smoke. If you do smoke, work with your healthcare provider on a plan to quit.
• Don’t drink alcohol. Alcohol can irritate the mucous lining of your stomach and duodenum.
• Don’t overuse nonsteroidal anti-inflammatory drugs (NSAIDs). Don’t take an NSAID for more than three days for fever or more than 10 days for pain unless your doctor says it’s OK.
• Consider switching pain relievers. If you use pain relievers that increase your risk of gastritis, ask your doctor whether acetaminophen (paracetamol) may be an option for you. This medicine is less likely to stir up your stomach and duodenum problem.
• Don’t consume food or drinks that irritate your gut. This includes gluten if you have celiac disease and foods you’re allergic to.

What foods should I eat or avoid with duodenal ulcer?

You can:

• Steer clear of foods that can irritate your gut, including spicy foods and highly acidic foods like citrus or tomato-based foods.
• Avoid drinks that can irritate your gut, including caffeinated drinks like coffee, tea or soda.
• Stop drinking alcohol or reduce your intake.

Try switching to bland foods until your symptoms improve. It’s a good idea to try the BRAT diet, which stands for bananas, rice, applesauce and toast. Gradually, you can include foods with a bit more nutritional value, like chicken soup and broth. Instead of eating big meals, aim for a few smaller meals spread out throughout the day so you’re not stressing your digestive system.

Regardless of what you eat, try not to eat anything three hours before bedtime. Allow your digestive system plenty of time to wind down so you can sleep easily.

What is duodenum

The duodenum is the first portion of the small intestine. The duodenum is the initial C-shaped segment of the small intestine and is a continuation of the pylorus (part of stomach) ⁷. Distally, duodenum is in continuation with the jejunum and ileum, with the proximal segment being the shortest and widest. Positioned inferiorly to the stomach, the duodenum is approximately 25 to 30 cm long. Interestingly enough, this portion of the small intestine got its name due to its length. In Latin, the term “duodenum” means 12 fingers, which is roughly the length of the duodenum. The 4 segments of the duodenum include the following:

1. The duodenal bulb, which connects to the undersurface of the liver via the hepatoduodenal ligament, which contains the portal vein, the hepatic artery, and common bile duct.
2. The second or descending segment is just above the inferior vena cava and right kidney, with the head of the pancreas lying in a C-shaped concavity.
3. The third segment runs from right to left in front of the aorta and inferior vena cava, with the superior mesenteric vessels in front of it.
4. The fourth segment continues as the jejunum.

The walls of the duodenum are made up of 4 layers of tissue that are identical to the other layers of the gastrointestinal (GI) tract. From innermost to the outermost layer, these are the mucosa, submucosa, muscularis, and serosa layers. The mucosal layer lines the inner surface of the duodenum and is made of simple columnar cells with microvilli and numerous mucous glands. The submucosal layer is mostly a layer of connective tissue where blood vessels and nerves travel through. The muscularis layer contains the smooth muscle of the duodenum and allow mixing and forward peristaltic movement of chyme. The serosal layer is characterized by squamous epithelium that acts as a barrier for the duodenum from other organs within the human body.

The duodenojejunal flexure is the sudden turn which is usually identified during surgery by the location of the inferior mesenteric vein, which is located to the immediate left. The duodenojejunal flexure is attached to the posterior abdominal wall by the ligament of Treitz. Except for the first segment, the rest of the duodenum is retroperitoneal and has no mesentery and is fixed to the posterior abdominal cavity.

The distal end of the common bile duct joins with the pancreatic duct to form the biliopancreatic ampulla which opens on the dome of the major duodenal papilla, located on the second segment of the C-shaped duodenum. This anatomical landmark is important for gastroenterologists as they do endoscopic retrograde cholangiopancreatography (ERCP) procedures to cannulate the major papilla of the duodenum.

Figure 1. Small intestine

Figure 2. Duodenum location

Figure 3. Relationship of the duodenum to the pancreas, liver and gallbladder

Figure 4. Duodenum anatomy

Figure 5. Duodenum anatomy (anatomical layers)

Figure 6. Duodenum blood supply

What does the duodenum do?

The duodenum is the mixing pot of the small intestine. Duodenum receives chyme from the stomach, which is a mixture of food products and acid, through a controlled valve between the stomach and the duodenum called the pylorus. Pancreatic enzymes enter the duodenum as well, releasing enzymes to break down the products from the stomach, and bicarbonate to neutralize the acid from the stomach before reaching the jejunum. Here the liver introduces bile which allows for the breakdown and absorption of fat from food products. The digestion inside of the duodenum is facilitated by the digestive enzymes and intestinal juices secreted by the intestinal wall as well as fluids received from the gallbladder, liver, and pancreas. This is received into the duodenum by the major and minor papilla in the second part of the duodenum. The duodenal papilla is surrounded by a semicircular fold superiorly and the sphincter of Oddi which is the muscle that prevents reflux of duodenal secretions into the bile and pancreatic ducts.

The duodenum also has the unique ability to regulate its environment with hormones that are released from the duodenal epithelium. One of those hormones is secretin, which is released when the pH of the duodenum decreases to a less than desirable level ⁷. The secretin hormone acts to neutralize the pH of the duodenum by stimulating water and bicarbonate secretion into the duodenum. In the duodenum there are tubular duodenal glands, whose ducts open into the intestinal crypts. These glands secrete an alkaline,
bicarbonate-rich mucus that helps neutralize the acidity of the chyme from the stomach and contributes to the protective layer of mucus on the inner surface of the small intestine. This also aids in the digestion process as pancreatic amylase and lipase require a certain pH to function optimally. Another hormone that is released by the duodenal epithelium is cholecystokinin (CCK). Cholecystokinin is released in the presence of fatty acids and amino acids inside of the duodenum and acts to inhibit gastric emptying and also to stimulate contraction of the gallbladder while simultaneously causing relaxation of the sphincter of Oddi to allow delivery of bile into the duodenum to aid in digestion and absorption of nutrients.

Duodenal ulcer causes

Duodenal ulcer is usually caused by a bacteria called Helicobacter pylori (H. pylori) ⁴, ⁸, ⁹, ¹⁰, ⁶, ⁵. Helicobacter pylori bacteria live in the mucous layer that covers and protects tissues that line your stomach and small intestine. The Helicobacter pylori (H. pylori) bacteria can inflame the protective lining of your duodenum, causing more stomach acid to be produced. If the protective lining of your duodenum is damaged, an duodenal ulcer can form.

It’s not clear how H. pylori infection spreads. It may go from person to person by close contact, such as kissing. People also can contract H. pylori through food and water.

Some medicines can also cause duodenal ulcers, particularly nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen and aspirin ⁵. They can sometimes harm the protective lining of your duodenum, allowing acid from your stomach to create an ulcer.

Other causes of duodenal ulcers include other medical conditions that disrupt the lining of your duodenum, such as Zollinger-Ellison syndrome (a rare condition in which one or more gastrin-secreting tumors called gastrinomas grow in the pancreas or small intestine produce large amounts of the hormone gastrin which causes the stomach to produce too much acid, leading to peptic ulcers), cancer, vascular insufficiency (a condition where blood vessels are unable to provide enough blood flow to the body’s tissues and organs), Crohn’s disease (a chronic inflammatory bowel disease that causes inflammation of the digestive tract) and history of chemotherapy ¹¹, ¹², ¹³.

There are some lifestyle factors that may make you more likely to get a duodenal ulcer, such as:

• Smoking. The chemicals from smoking tobacco can irritate your gut.
• Drinking a lot of alcohol. Too much alcohol can irritate and eat away the mucous lining in your stomach and intestines. And it increases stomach acid. This can cause the lining to inflame and bleed.
• Stress. Stress may make the symptoms of a peptic ulcer worse. Think about what causes your stress and what you can do to ease it. There are many ways to cope with stress. These include exercise, spending time with friends, deep breathing, writing in a journal or meditating.

However, these factors are usually not the main cause of duodenal ulcers. Stress and spicy foods do not cause peptic ulcers, but they can make your symptoms worse.

Duodenal ulcer pathophysiology

The mechanism by which Helicobacter pylori (H. pylori) bacteria predisposes individuals to developing duodenal ulcer is unclear ¹. However, the thinking is that H. pylori colonization and persistent inflammation lead to the weakening of the mucosal surface layer causing it to be vulnerable to exposure to gastric acid ¹. A secondary running theory considers the possibility that H. pylori also can increase acid production via inflammatory mechanisms, further exacerbating the initial injury caused by the infection and initial acid-driven injury ¹⁴.

Prostaglandins play a crucial role in developing the protective mucosa in the gastrointestinal tract, including gastric and small intestine mucosa. Prostaglandins biosynthesis is catalyzed by the enzyme cyclooxygenase (COX), which exists in two isoforms, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit their therapeutic effect by inhibiting the COX-1 and COX-2 pathways. Recurrent use of NSAIDs causes a significant and persistent decrease in prostaglandins leading to susceptibility to mucosal injury. It is thought to be one of the primary predisposing pathophysiologic factors for the development of duodenal ulcers ¹⁵.

Other secondary causes for duodenal ulcers may work through different underlying mechanisms. However, the ultimate result is generally recurrent mucosal injury that predisposes the tissue to ulceration or an elevation in the amount of acid the mucosa is exposed to, which in turn causes tissue damage.

Duodenal ulcer signs and symptoms

Duodenal ulcer doesn’t always cause symptoms, up to 70%, are asymptomatic ¹⁶, ¹. When it does, people experience duodenal ulcer differently. People with duodenal ulcers usually complain of abdominal pain 2 to 3 hours after eating a meal on an empty stomach or abdominal pain that improved after eating, whereas people with stomach ulcers complain of nausea, vomiting, weight loss, and abdominal pain after eating.

Duodenal ulcer symptoms may include:

• Upper abdominal pain (abdominal pain 2 to 3 hours after eating a meal on an empty stomach or epigastric abdominal pain that improved after eating).
• Bloating (tight, full or painful feeling in your upper abdomen after eating).
• Nausea and vomiting.
• Diarrhea.
• Fatigue.
• Gas.
• Loss of appetite.
• Weight loss.

Bleeding in your digestive tract is sometimes a sign of severe duodenal ulcer. Signs include:

• Blood in your vomit (may look like coffee grounds).
• Blood in your poop (may look dark-colored or tarry).
• You have a sharp pain in your stomach that doesn’t go away.
• Feeling dizzy or fainting.

You should see a doctor if you notice these signs, which may mean you have duodenal ulcer or another digestive system condition that needs treatment.

Duodenal ulcer complications

If left untreated, your duodenal ulcer may get worse. This can cause other complications, such as:

• Bleeding ulcer — this can vary from a small trickle to a serious, life-threatening bleed
• Perforated duodenum — this is when the ulcer goes through the wall of your duodenum, causing food and acid to leak into your belly ¹⁷. The mortality rate from duodenal perforation ranges from 8% to 25% in the literature ¹⁸, ¹⁹, ²⁰
• Gastric outlet obstruction also known as an intestinal obstruction that occurs when scar tissues in your duodenum block the passage of food or liquid through the small intestine.
• Stomach cancer. Studies have shown that people infected with H. pylori have an increased risk of stomach cancer ²¹, ²², ²³, ²⁴.

These complications require emergency treatment and can cause sharp pain, bloody vomit or bloody stools (poop).

For patients who present with bleeding, the majority are manageable via endoscopic intervention. However, a minority of patients will require surgical intervention. Patients who require surgical intervention fail endoscopic intervention, ones with large ulcers or hemodynamically unstable patients despite adequate resuscitation ²⁵. A small percentage of patients, 2% to 10% of them with peptic ulcer disease, will present with perforation. These patients generally present with very severe diffuse abdominal pain that may start as epigastric pain and become generalized ²⁶. Surgical intervention merits consideration in patients with perforated ulcers. However, a small percentage of those affected may experience spontaneous sealing of the perforation. Gastric outlet obstruction is the least common complication associated with duodenal ulcers, and studies regarding management and diagnosis are limited.

Duodenal ulcer diagnosis

Your doctor is likely to suspect duodenal ulcer after talking to you about your medical history and performing an exam. If your doctor suspects duodenal ulcer, he/she will perform tests to figure out what’s causing the duodenal ulcer. Tests may include:

• Tests for H. pylori. Your doctor may recommend tests such as a stool test or breath test to determine whether you have H. pylori infection. Which type of test you have depends on your situation. For the breath test, you drink a small glass of clear, tasteless liquid that contains radioactive carbon. H. pylori germs break down the test liquid in your stomach. Later, you blow into a bag, which is then sealed. If you’re infected with H. pylori, your breath sample will contain the radioactive carbon.
• Blood tests: A blood sample can show if you have a germ, like H. pylori, that’s causing an infection. A blood test can also show if you have antibodies for gluten as in celiac disease. Antibodies are proteins your immune system makes to fight germs. Antibody blood tests are usually the first tests that are ordered to diagnose celiac disease. These tests look for proteins created during the body’s immune response, known as antibodies, that are present in most people with celiac disease.
• Stool test: Your poop can show if you have an H. pylori infection.
• Passing a thin, flexible scope down the throat, called an upper endoscopy. Endoscopy is a procedure to examine the digestive system with a long, thin tube with a tiny camera, called an endoscope. The endoscope passes down the throat, into the esophagus, stomach and small intestine. Using the endoscope, your doctor looks for signs of inflammation. The scope contains instruments that can take tissue samples for lab testing. Depending on your age and medical history, your doctor may recommend this as a first test instead of testing for H. pylori.
• Upper GI series: This series of X-rays takes images of your upper digestive system. You may have to swallow a white, metallic liquid that contains barium. The liquid coats your digestive tract and makes an ulcer more visible. This procedure is called a barium swallow. It can show how these organs work together so your doctor can better understand what’s causing inflammation in your duodenum.

If a suspicious area is found, your doctor may remove small tissue samples, called a biopsy, to test in a lab. A biopsy also can identify the presence of H. pylori in your duodenum lining.

Duodenal ulcer treatment

Treatment for duodenal ulcers involves killing the H. pylori germ, if needed. If your duodenal ulcer is caused by H. pylori infection, the usual treatment is ‘triple therapy’. This means taking 2 antibiotics and a proton pump inhibitor (PPI) medicine. The antibiotics kill the bacteria, while the proton pump inhibitor (PPI) medicine reduces the acid made by your stomach.

If you don’t have an H. pylori infection and you have been using anti-inflammatory medicines (NSAIDs), you might be advised to stop taking them if possible. You will also need to start taking a proton pump inhibitor (PPI) medicine to reduce the acid production in your stomach to help the ulcer heal.

Duodenal ulcer treatment can include:

• Antibiotics to kill H. pylori. If you have H. pylori in your digestive tract, your healthcare professional may suggest a mix of antibiotics. These may include amoxicillin (Amoxil, Larotid), clarithromycin (Biaxin XL), metronidazole (Flagyl, Likmez), tinidazole (Tindamax), tetracycline and levofloxacin.
• Medicines that block acid. Proton pump inhibitors (PPIs) reduce stomach acid. Proton pump inhibitors (PPIs) include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), esomeprazole (Nexium) and pantoprazole (Protonix). Most people take proton pump inhibitors (PPIs) in pill form. In the hospital, treatment for a bleeding ulcer may involve a PPI given through a vein in the arm. This is known as intravenous delivery. Note that long-term or high-dose use of proton pump inhibitors (PPIs) may increase your risk of hip, wrist and spine fracture. Ask your doctor whether a calcium supplement may reduce this risk.
• Medicines to reduce stomach acid. Acid blockers, also called histamine (H-2) blockers, help relieve ulcer pain and help with healing. Acid blockers include famotidine (Pepcid AC), cimetidine (Tagamet HB) and nizatidine (Axid AR).
• Antacids that counter the effects of stomach acid. These can relieve pain quickly. But they aren’t used to heal ulcers. Side effects can include constipation or diarrhea, depending on the main ingredients in the antacids.
• Medicines that protect the lining of the stomach and small intestine. These are called cytoprotective agents. They include the prescription medicines sucralfate (Carafate) and misoprostol (Cytotec).

You can make some other lifestyle changes to improve your symptoms, such as:

• Not drinking alcohol
• Losing weight if you are living with obesity
• Quit smoking if you smoke
• Having your evening meals a few hours before bedtime
• Avoiding triggering foods such as coffee, fatty foods, spicy foods and acidic foods such as tomato.

Helicobacter pylori Infection Treatment

Regimens for eradication of Helicobacter pylori infection are typically chosen empirically, on the basis of regional bacterial resistance patterns, local recommendations, and drug availability ²⁷. Therapy for Helicobacter pylori infection has undergone major changes, based on application of the principles of antimicrobial stewardship and increased availability of susceptibility testing. Common initial choices for empiric treatment include a 14-day bismuth-based quadruple therapy or rifabutin-based triple therapy. However, clinicians should use regimens shown to be highly effective locally ²⁷. In addition, doctors should ask their patients about any prior antibiotic use or exposure, and take that information into consideration in the choice of a treatment regimen ²⁸.

The following regimens are described below ²⁹:

• Triple therapy
  • Proton pump inhibitor (PPI) based triple therapy for H. pylori infection remains an option for first-line therapy in areas of low (< 15%) clarithromycin resistance and consists of the following ³⁰, ³¹, ²⁸, ³², ³³, ³⁴, ³⁵:
    • Proton pump inhibitor (PPI) (e.g., omeprazole 20 mg BID, lansoprazole 30 mg BID, esomeprazole 40 mg QD, pantoprazole 40 mg QD, rabeprazole 20 mg BID) PLUS
    • Clarithromycin 500 mg BID (first-line and continues to be recommended in areas where H. pylori clarithromycin resistance is less than 15% and in patients without previous macrolide exposure​) or metronidazole 500 mg BID (when clarithromycin resistance is increasing) PLUS
    • Amoxicillin 1000 mg BID or metronidazole 500 mg BID (if not already selected)
    • Duration: A Cochrane meta-analysis of 55 studies concluded that 14 days is the optimal duration of triple therapy, achieving an H. pylori eradication rate of 81.9%, whereas 7 days attains an eradication rate of only 72.9% ³⁶. In more recent studies, the H. pylori eradication rate with 14-day triple therapy is not significantly different from that with 10-day sequential therapy (amoxicillin and a PPI for 5 days followed by a PPI, clarithromycin and metronidazole for another 5 days) or 10-day concomitant non-bismuth quadruple therapy ³⁷, ³⁸.
• Non-bismuth quadruple therapy
  • Non-bismuth quadruple therapy may be given sequentially or concomitantly ²⁹, ²⁸:
    • Sequential therapy
      • Sequential therapy (a suggested first-line option) is superior to standard triple therapy, according to two systematic reviews and consists of the following ³⁹, ⁴⁰:
        • Proton pump inhibitor (PPI) plus amoxicillin for 5-7 days (eg, pantoprazole 40 mg BID and amoxicillin 1 g BID for 7 days), then PPI plus 2 other antibiotics for the next 5-7 days; clarithromycin and metronidazole are the antibiotics usually chosen, but levofloxacin-based regimens (see below) and tetracycline-based regimens (eg, pantoprazole 40 mg BID, tetracycline 500 mg QID, and metronidazole 500 mg BID) [22] are superior to 14-day triple therapy, based on a meta-analysis of 21 trials ³⁹, ⁴¹, ⁴², ⁴³. Eradication rates with different durations of sequential therapy are as follows:
          • 14 days: 90.7-92.5% H. pylori eradication rates ⁴⁴, ⁴⁵
          • 10 days: 87% H. pylori eradication rate ⁴⁴, ²⁸, ³²
    • Concomitant therapy
      • Concomitant therapy is better for clarithromycin-resistant H. pylori strains and 14 days of concomitant therapy is superior to 14-day triple therapy, with cure rates of ≥90% ⁴⁶, ⁴⁷, ⁴⁸, ⁴⁹, ⁵⁰, ⁵¹.
      • Concomitant therapy (an alternative first-line option) consists of the following (using dosages similar to those in triple therapy; or all drugs BID in one study):
        • Proton pump inhibitor (PPI) plus
        • Amoxicillin plus
        • Clarithromycin (1 g modified-release tablet QD in one study) plus
        • Metronidazole (500 mg TID in one study)
        • Duration of concomitant therapy is 10-14 days ⁴⁷, ⁵², ²⁸
      • Novel concomitant therapy consists of the following agents, which are given for 10 days ⁵³:
        • PPI (eg, rabeprazole 20 mg TID) plus
        • Amoxicillin 1 g TID for 10 days (or, if penicillin allergic, bismuth subcitrate 240 mg QID plus
        • Rifabutin 150 mg BID plus
        • Ciprofloxacin 500 mg BID
        • A small randomized trial in Taiwan reported that 14-day high-dose dual therapy with esomeprazole (40 mg TID) and amoxicillin (750 mg QID) as first-line treatment yielded an eradication rate similar to that of a 7-day non-bismuth quadruple therapy ⁵⁴.
    • Hybrid therapy
      • Hybrid therapy is a combination of sequential and concomitant therapy as follows ²⁹, ⁵⁵, ⁵⁶:
        • Proton pump inhibitor (PPI) plus amoxicillin for 3-7 days (the latter recommended as another suggested first-line option in the 2017 American College of Gastroenterology guideline), then proton pump inhibitor (PPI) plus amoxicillin plus 2 other antibiotics (usually, clarithromycin and metronidazole) for 7 days
        • There is evidence that H. pylori eradication rates with 10-day, 12-day, and 14-day regimens are comparable, at 95.0%, 95.1%, and 93.4%, respectively. This suggests that the optimal duration of hybrid therapy is 12 days, since high rates of eradication are still achieved.
        • When compared with 14 days of bismuth-containing quadruple therapy, a 14-day hybrid therapy regimen (7 days of dual therapy with pantoprazole plus amoxicillin, followed by 7 days of quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole) showed comparable drug adherence and eradication rates, but with a significantly lower rate of adverse effects (15.7%, versus 55.5% with bismuth-containing quadruple therapy) ⁵⁷.
    • Reverse hybrid therapy
      • Reverse hybrid therapy is a combination of sequential and concomitant therapy, using the same drugs as hybrid therapy but in reverse sequence, as follows ⁵⁶:
        • Proton pump inhibitor (PPI) plus amoxicillin plus 2 other antibiotics (usually, clarithromycin and metronidazole) for 7 days then
        • Proton pump inhibitor (PPI) plus amoxicillin for 3–7 days
        • Helicobacter pylori eradication rate achieved with 12 days of reverse hybrid therapy is similar to that with 12 days of hybrid therapy (95.7% vs. 95.1%, respectively). Fourteen-day reverse hybrid therapy as first-line treatment has equivalent efficacy but less adverse effects than 14-day concomitant therapy, according to a randomized, controlled trial from Taiwan ⁵⁸.
• Bismuth-based therapy
  • Bismuth-based therapy is an alternative first-line therapy (in areas with high clarithromycin and metronidazole resistance, and in patients with prior macrolide exposure or penicillin-allergic) or second-line therapy (see below). Bismuth-based therapy consists of the following ⁵⁹, ⁶⁰, ³⁸, ³²:
    • Proton pump inhibitor (PPI) or H2 receptor antagonist (eg, lansoprazole 30 mg BID or famotidine20 mg BID) plus
    • Bismuth subsalicylate 525 mg QID (or bismuth tripotassium dicitrate 300 mg QID) plus
    • Metronidazole 250 mg QID or 500 mg TID (or levofloxacin 500 mg QD) plus
    • Tetracycline 500 mg QID
    • Duration is 10-14 days. The Helicobacter pylori eradication rate was 90.4% for 10 days of bismuth quadruple therapy, while extending therapy to 14 days achieved an eradication rate of 97.1% ⁶¹.
    • Chinese researchers reported that the following regimen provides effective first-line treatment in a population with high antibiotic resistance ⁶²:
      • Rabeprazole 10 mg BID plus
      • Bismuth potassium citrate 220 mg BID plus
      • Amoxicillin 1000 mg BID plus
      • Clarithromycin 500 mg BID
      • Duration is 10 days. Rabeprazole and bismuth were given 30 min before the morning and evening meals. Antibiotics were given 30 min after the morning and evening meals ⁶².
    • Researchers in Turkey, however, reported that a 14-day regimen of lansoprazole 30 mg BID, amoxicillin 1000 mg BID, clarithromycin 500 mg BID, bismuth subsalicylate 600 mg BID was not significantly superior to a 7-day regimen (81.4% vs. 80%) ⁶³.
• Levofloxacin-containing therapy
  • Levofloxacin-containing therapy is an alternative first-line regimen and consists of a proton pump inhibitor (PPI) plus amoxicillin 1 g BID plus levofloxacin 500 mg QD ⁶⁴, ³², ⁴².
  • Duration options are as follows:
    • 7 days (eradication rates of up to 80.9%) ⁴², ⁶⁴, ⁶⁵
    • 10 days (eradication rates of up to 83.1%) ⁶⁶
    • 10-14 days is recommended by the 2017 American College of Gastroenterology guidelines ²⁸
  • Sequential therapy, an alternative first-line regimen, is as follows (eradication rates of up to 86.5%):
    • Proton pump inhibitor (PPI) (esomeprazole 20 mg or 40 mg BID) plus amoxicillin (1 g BID) for 5-7 days, then
    • Proton pump inhibitor (PPI) (esomeprazole 20 mg or 40 mg BID) plus levofloxacin (250 mg or 500 mg BID) plus a nitroimidazole antibiotic (eg, tinidazole 500 mg BID) for 5-7 days
    • A randomized trial investigated the role of bismuth in levofloxacin-containing 14-day sequential therapy, and concluded that adding bismuth did not significantly improve eradication rates (85.2% vs. 82.6%).
  • Concomitant therapy, another alternative first-line regimen, is as follows (eradication rates of up to 96.5%) ⁶⁷: proton pump inhibitor (PPI) (esomeprazole 40 mg BID) plus amoxicillin (1 g BID) plus levofloxacin (500 mg QD) plus another antibiotic (eg, tinidazole 500 mg BID) for 5 days.
• Concomitant bismuth- and levofloxacin-containing therapy
  • A group of Chinese researchers reported that the following concomitant bismuth- and levofloxacin-containing therapy regimen also provided satisfactory eradication rates in a population with high antibiotic resistance ⁶⁸:
    • Esomeprazole 20 mg BID plus
    • Levofloxacin 500 mg BID plus
    • Bismuth 220 mg BID plus
    • Amoxicillin 1000 mg BID or cefuroxime 500 mg BID
    • Duration: 14 days. Eradication rates were not significantly different between the amoxicillin and cefuroxime groups (83.5% vs 81%) ⁶⁸.
  • An open-label, randomized trial conducted in China reported acceptable eradication rates even for the following 1-week bismuth-containing regimen ⁶⁹:
    • Esomeprazole 20 mg BID plus
    • Colloidal bismuth pectin 200 mg BID plus
    • Amoxicillin 1000 mg BID plus
    • Levofloxacin 500 mg OD or clarithromycin 500 mg BID
    • The above levofloxacin-based concomitant quadruple regimen demonstrated a higher eradication rate (86.66% vs 76.22%) ⁶⁹.
• Second-line therapy
  • Second-line therapy should avoid repeating first-line regimens that were already used, and should incorporate at least one different antibiotic ⁷⁰, ²⁹. Bismuth-based therapy or levofloxacin-containing triple therapy can be used (same regimens as above, if not used previously) ⁷⁰.
  • In a meta-analysis of 115 heterogeneous studies, per protocol analysis showed that quadruple therapies have better cure rate than triple (83% vs 76%) and 14-day quadruple treatment than 7-day regimens (91% vs 81%) ⁷¹.
• Rescue or third-line therapy
  • Rifabutin-based therapy is recommended as rescue or salvage therapies when first-line agents fail ³¹, ²⁸. A rifabutin-based triple-therapy regimen consists of the following three agents given together every 8 hours for 14 days ⁷²:
    • Amoxicillin 1 g plus
    • Omeprazole 40 mg plus
    • Rifabutin 50 mg
    • Rifabutin-based therapy regimen is available prepackaged as Talicia. The US Food and Drug Administration (FDA) approved Talicia for treatment of H. pylori infection in 2019, based in part on results of two phase 3 studies that showed eradication rates of 84.1% and 90.3% ⁷², ⁷³.
  • Vonoprazan-based therapy is yet to be included in the H. pylori treatment guidelines. Vonoprazan triple therapy has been proposed as an alternative first-line regimen for clarithromycin-sensitive strains, given its similar or greater effectiveness as proton pump inhibitors (PPIs) ⁷⁴, ⁷⁵. The first potassium-competitive acid blocker (PCAB)–based therapy was approved by the FDA in May 2022 and consists of triple therapy for 14 days with the following ⁷⁶:
    • Vonoprazan (PCAB) 20 mg BID plus
    • Amoxicillin 1000 mg BID plus
    • Clarithromycin 500 mg BID
    • Vonoprazan-based therapy regimen has been packaged in the Voquezna Triple Pak. Vonaoprazan plus amoxicillin was also approved by the FDA and has been packaged in the Voquezna Dual Pak. However, neither product has been released on the market, due to the detection of trace levels of a nitrosamine impurity ⁷⁷.

Duodenal ulcers that don’t heal

Duodenal ulcers that don’t heal with treatment are called refractory ulcers. Reasons for an ulcer not healing include:

• Not taking medicines as prescribed.
• Having a type of H. pylori that resists antibiotics.
• Often using pain relievers, such as nonsteroidal anti-inflammatory drugs (NSAIDs), that increase the risk of ulcers.

Less often, refractory ulcers may be a result of:

• A lot of stomach acid, such as happens in Zollinger-Ellison syndrome.
• An infection other than H. pylori bacteria.
• Stomach cancer.
• Other conditions that may cause ulcerlike sores in the stomach and small intestine, such as Crohn’s disease a type of inflammatory bowel disease (IBD) that causes chronic inflammation in the digestive tract ⁷⁸, ⁷⁹. Crohn’s disease can affect any part of your digestive system, but often affects the last part of the small intestine (ileum) and the colon (large intestine). Symptoms include diarrhea, abdominal pain, fatigue, and weight loss.

Treatment for refractory ulcers most often involves getting rid of factors that keep the ulcer from healing and trying other antibiotics. If you smoke, your doctor may suggest you quit. Smoking can slow ulcer healing.

A serious complication from an ulcer, such as bleeding or a hole in your duodenum, may need treatment with endoscopy or surgery. But because there are many medicines that work well, people with duodenal ulcers need surgery far less often than in the past.

Duodenal ulcer prognosis

Duodenal ulcer prognosis (outlook) is variable depending on the severity of the initial presentation. Duodenal ulcers primarily caused by nonsteroidal anti-inflammatory drug (NSAID) use are addressable through discontinuation of the drug and therapy for symptoms with high rates of resolution. Individuals who have developed ulcers due to H. pylori infection will require treatment of the infection, and rates of resolution will vary based on the eradication of infection. Patients who present with severe ulceration or perforation will have higher mortality rates and will be at risk for complications associated with surgical intervention.

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