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Peptic ulcers and stomach cancer: Clinical practice

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Peptic ulcers and stomach cancer: Clinical practice

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A 52-year-old man comes to the emergency department because of severe abdominal pain.  He has felt this pain for months, but it has become intolerable over the last 7 hours. He has a history of gastroesophageal reflux disease (GERD), hypertension, and diabetes. He says that eating exacerbates the pain. He thought he was just having some indigestion and would take some antacids for relief. However, since the pain worsened, he is now having trouble moving. His temperature is 39.1°C (102.5°F), pulse is 115/min, and blood pressure is 135/75 mm Hg. He appears to be in severe distress, secondary to pain, and refuses to straighten his legs because it hurts too much. He has diffuse guarding and rebound tenderness. An upright chest radiograph shows free air under the right diaphragm. Which of the following is the most likely cause of the patient’s symptoms?

Transcript

Content Reviewers:

Rishi Desai, MD, MPH

Peptic ulcers are deep erosions in the lining of the stomach or duodenum that lead to inflammation in the gastric or duodenal wall.

Sometimes, peptic ulcers develop acutely like after a toxic ingestion or ischemia, but more often the erosions are chronic, developing slowly over time.

Chronic ulcers are mostly benign, but they can sometimes develop into a malignant ulcer, termed stomach cancer, which is why an upper endoscopy with biopsy is essential to the diagnosis.

Chronic ulcers sometimes don’t cause any symptoms. When they do, the most common symptom is dyspepsia.

Dyspepsia includes epigastric pain related to eating food, early satiety, postprandial belching, and nausea.

With gastric ulcers, epigastric pain worsens when eating a meal because of the hydrochloric acid that’s produced in response to food.

With duodenal ulcers, epigastric pain is relieved while eating a meal, but it typically recurs 2 to 5 hours later or it can appear at night. That’s because with duodenal ulcers, Helicobacter pylori is involved in most cases and it increases the hydrochloric acid production by indirectly increasing gastrin production and when there’s no food to act as a buffer, the pain worsens.

Sometimes peptic ulcers can erode deep into the gastric and duodenal wall resulting in complications.

If an ulcer erodes into a blood vessel, then it can cause hematemesis or melena.

If there’s an ulcer in the pyloric antrum or in the duodenum, then it can cause gastric outlet obstruction. That can worsen the symptoms and even cause the individual to lose weight.

Peptic ulcers can also perforate into the peritoneal cavity causing peritonitis, and that causes severe abdominal pain and fevers.

With stomach cancer, things get a little more complicated. Risk factors include chronic mucosal inflammation, like in Helicobacter pylori infection, atrophic gastritis, and surgery on the stomach; as well as environmental triggers like tobacco, and occupational exposures to coal, steel, or iron.

There are many types of stomach cancer, but the most frequent one is adenocarcinoma and this is found in 90% of the cases.

However, a MALT lymphoma which stands for mucosal-associated lymphoid tissue lymphoma can develop when there’s persistent antigenic stimulation of the gastric mucosa like in a Helicobacter pylori infection.

Symptoms of stomach cancer usually appear in advanced stages and includes unintended weight loss, diffuse abdominal pain, hematemesis or melena and a sense of fullness in the upper abdomen after eating a small meal.

When a peptic ulcer is suspected, barium radiography, which uses barium as contrast, can sometimes be done.

On barium radiography, a peptic ulcer looks round or oval, and it’s surrounded by edematous mucosal folds which radiate towards the ulcer.

In contrast, a malignant ulcer is more irregular and the mucosal folds don’t usually reach the margin of the ulcer.

Nowadays, barium radiography is not commonly done, because an upper endoscopy is better for diagnosing a peptic ulcer and distinguishing it from stomach cancer. However, if the Barium radiography is done and shows a peptic ulcer, then an upper endoscopy isn’t usually needed.

On the other hand, if the barium radiography is inconclusive or if it simply isn’t done at all, then an upper endoscopy is done.

Normally, a peptic ulcer looks like a crater that has smooth margins and a flat base that may contain exudate.

In contrast a malignant ulcer looks like a crater that has thick and irregular margins with a mass resting within the base.

In addition, the mucosa surrounding the malignant ulcer is often nodular and necrotic.

A biopsy of the erosion must be obtained to confirm whether it’s a peptic ulcer or a malignant ulcer.

Usually, duodenal ulcers rarely cause cancer and are biopsied only when the appearance suggests malignancy, but gastric ulcers develop into stomach cancers more frequently, so they should always be biopsied.

Along with the biopsy, Helicobacter pylori testing should be done, because it’s a risk factor for peptic ulcers, stomach cancer, and MALT lymphoma.

On biopsy, a newly formed acute peptic ulcer has regular margins and has inflammatory exudate with neutrophils, and it’s considered active if it’s bleeding.

If it’s a chronic peptic ulcer then it typically has lymphocytes, and some signs of fibrinoid necrosis and new granulation tissue at the base and margins.

In contrast, a malignant ulcer looks different depending on the type of cancer.

Gastric adenocarcinoma is split up into the intestinal subtype which has cells that look like intestinal cells or the diffuse subtype which has cells that secrete mucus.

With MALT lymphoma, there are an abundance of B-cells which can be identified by cell surface markers, like CD20.

If a gastric adenocarcinoma has been confirmed on the biopsy, then a CT scan of the thorax, abdomen, and pelvis is done to stage the stomach cancer. The findings are then classified in the Tumor-Nodes-Metastasis or TNM system.

Gastric adenocarcinoma has 5 stages, from 0 to 4, 0 meaning only the gastric mucosa is infiltrated and 4 meaning there are distant metastasis.

In the first two stages of cancer- 0 and 1, an endoscopic resection of the cancer can be done or else a subtotal or total gastrectomy is indicated, meaning that a part of the stomach or the entire stomach is surgically removed.

In stage 2 and 3, chemotherapy is used before or after the surgery to shrink the tumor and lower the chances of the cancer coming back and then a total gastrectomy is done. In this situation, the omentum and the nearby lymph nodes are also removed. If the individual cannot undergo surgery, then chemoradiation may be used.

In stage 4 disease, palliative surgery like a gastric bypass or a subtotal gastrectomy, along with chemoradiation, is used to relieve symptoms.

If the biopsy and immunohistochemistry showed a MALT lymphoma, a CT scan of the neck, thorax, abdomen and pelvis is done to stage the cancer, and H.pylori serology is done if it wasn’t already detected on the biopsy. Then the MALT lymphoma is staged using the Lugano classification into 4 stages, where stage 1 means that the cancer is confined in the gastrointestinal tract and stage 4 means that the cancer spread to distant organs or in the lymph nodes of both sides of the diaphragm.

Treatment depends on whether H. pylori is present or not.

With stage 1 and 2 MALT lymphomas that are H.pylori positive, treatment is eradication of the H.pylori infection, and this alone can induce regression of the cancer.

If H.pylori is not present or if the eradication of H.pylori with different treatment regimens repeatedly fails over the course of a year, then radiation therapy, chemotherapy or immunotherapy can be tried.

With stage 3 and 4 MALT lymphomas, that are either H.pylori positive or H.pylori negative, the treatment consists of chemotherapy or immunotherapy.

Now, let’s say that instead of stomach cancer, we’re dealing with peptic ulcers. The most common cause of peptic ulcers is colonization with Helicobacter pylori. This is a gram negative bacteria that makes a home for itself in the stomach by releasing proteases that injure the surrounding mucosa.