Zollinger-Ellison syndrome

　　It is a comprehensive disease mainly manifested by gastrointestinal ulcers. It ranks second in incidence among pancreatic endocrine tumors, following insulinoma. 60% to 70% are malignant and often accompanied by lymph node or liver metastasis. 25% to 30% of patients have other endocrine tumors at the same time [multiple endocrine neoplasia type I (MEN-I)]. Some tumors are located outside the pancreas, with the duodenum as the most common site. The cause is gastrinoma of the gastric G cells. Due to the tumor's ability to secrete large amounts of gastrin, it stimulates the extreme increase in gastric acid secretion, leading to refractory atypical ulcers that are prone to bleeding and perforation. It is often accompanied by parathyroid or pituitary adenomas and their corresponding symptoms.

　　1. Massive hemorrhage

　　This is the most common complication of the disease, with an incidence rate of about 20% to 25% of patients with the disease, and it is also the most common cause of upper gastrointestinal bleeding. It is more common in gastric ulcers than in duodenal ulcers, and even more common in retrograde ulcers. For those with bleeding, the history of Zollinger-Ellison syndrome is usually within one year, but after one bleeding episode, it is easy to have a second or more bleeding episodes. There are also 10% to 15% of patients whose first symptom of Zollinger-Ellison syndrome is massive bleeding.

　　The clinical manifestations of Zollinger-Ellison syndrome bleeding depend on the location, speed, and amount of bleeding. For example, in the posterior wall of the duodenal ulcer, it often perforates the adjacent pancreaticoduodenal artery, resulting in massive and rapid bleeding; while the anterior wall, as there is no large artery adjacent to it, is less likely to cause massive bleeding. Bleeding from the granulation tissue at the base of the ulcer or hemorrhagic erosion around the ulcer usually only causes small and temporary bleeding. For those with rapid and massive bleeding in Zollinger-Ellison syndrome, the manifestations are hematemesis and melena; if the bleeding is less and slow and persistent, it can manifest as gradually appearing hypochromic microcytic anemia and positive fecal occult blood. Hemorrhage from duodenal ulcers is more common than hematemesis, while for gastric ulcer hemorrhage, both occur with similar frequency. Massive bleeding in a short period of time can cause dizziness, blurred vision, weakness, thirst, palpitations, tachycardia, blood pressure drop, fainting, and even shock due to a sharp decrease in blood volume. Before the occurrence of bleeding in Zollinger-Ellison syndrome, the pain in the upper abdomen often worsens due to the sudden increase in congestion locally. After bleeding, abdominal pain can be relieved due to reduced congestion and the neutralizing and diluting effects of alkaline blood on gastric acid.

　　Diagnosis is generally not difficult to establish based on the history of Zollinger-Ellison syndrome and clinical manifestations of bleeding. For those with atypical clinical manifestations and difficult diagnosis, it is advisable to undergo emergency endoscopic examination within 24 to 48 hours after bleeding, with a diagnostic rate of over 90%, thereby enabling timely diagnosis and treatment for the patient.

　　2. Perforation

　　Perforation through the serosal layer of the ulcer into the free peritoneal cavity can lead to acute perforation; if the ulcer perforates and adheres to adjacent organs or tissues, it is called a penetrating ulcer or chronic perforation of the ulcer. When the posterior wall perforates or the perforation is small and only causes localized peritonitis, it is called subacute perforation.

　　During acute perforation, due to the entry of duodenal or gastric contents into the abdominal cavity, it leads to acute diffuse peritonitis, and sudden onset of severe abdominal pain in clinical practice. The pain usually starts in the upper right or midupper abdomen and quickly spreads to the umbilical area, and even the whole abdomen. Since the leaked contents of the gastrointestinal tract stimulate the diaphragm, the pain can radiate to one side of the shoulder (usually the right side). If the leaked contents flow along the root of the mesentery into the right lower pelvic cavity, it can cause pain in the right lower abdomen, resembling an acute appendicitis perforation. Abdominal pain can be exacerbated by actions such as turning over or coughing, so patients often prefer to lie in bed with their legs curled up and do not want to move. Abdominal pain is often accompanied by nausea and vomiting. Patients are usually restless, pale, with cold limbs, and tachycardia. If perforation occurs after a heavy meal, a large amount of gastric contents may leak out, leading to marked rigidity of the abdominal muscles, as well as tenderness and rebound pain all over the abdomen; if the amount of leakage is less, rigidity, tenderness, and rebound pain can be localized to the midupper abdomen. The sound of bowel sounds is reduced or absent. The liver dullness border is reduced or disappears, indicating the presence of pneumoperitoneum. If gastrointestinal contents reach the pelvic cavity, rectal examination can detect tenderness in the right rectal凹陷. The total white blood cell count and neutrophils in peripheral blood increase. Abdominal X-ray examination often shows free gas under the diaphragm, thereby confirming the presence of gastrointestinal perforation; however, the absence of free gas under the diaphragm does not rule out the presence of a perforation. In severe cases of perforation or when the ulcer penetrates and involves the pancreas, serum amylase levels may also increase, but usually not more than 5 times the normal value.

　　The symptoms of subacute or chronic perforation are not as severe as those of acute perforation. They can only cause localized peritonitis, intestinal adhesion, or signs of intestinal obstruction, and can improve within a short period of time.

　　3. Pyloric Obstruction

　　Mostly caused by duodenal ulcers, but can also occur in prepyloric and pyloric canal ulcers. The cause is usually due to the activity period of the ulcer, inflammatory congestion, edema, or reflex pyloric spasm around the ulcer. This type of pyloric obstruction is temporary and can disappear with the improvement of the ulcer; therefore, it is called functional or medical pyloric obstruction as it is effective with medical treatment. Conversely, the ones caused by the healing of the ulcer, the formation of scars, the contraction of scar tissue, or adhesion with surrounding tissues to block the pyloric channel are persistent and cannot be automatically relieved without surgical intervention, and are called organic and surgical pyloric obstruction. Due to gastric retention, patients may feel discomfort and fullness in the upper abdomen, and often accompanied by symptoms such as decreased appetite, belching, acid regurgitation, and other gastrointestinal symptoms, especially after meals. Vomiting is the main symptom of pyloric obstruction, usually occurring 30 to 60 minutes after meals. The frequency of vomiting is not high, about once every 1 to 2 days. The amount of vomiting in one episode can exceed 1L, containing fermented retained food. Patients may experience significant weight loss due to long-term, frequent vomiting and decreased intake of food. However, not all patients have abdominal pain, and if they do, it often occurs in the morning and is not rhythmic. Due to repeated and large-scale vomiting, there may be a significant loss of H+ and K+, leading to metabolic alkalosis, and symptoms such as shortness of breath, weakness of the limbs, restlessness, and even tetany. The characteristic signs of pyloric obstruction include abdominal fullness and retrograde peristalsis in the upper abdomen when fasting, as well as tympany in the upper abdomen.

　　Symptoms of peptic ulcers are the most common, with poor response to ulcer treatment drugs. After subtotal gastrectomy for ulcers, anastomotic ulcers, bleeding, and perforation quickly appear, followed by diarrhea, watery stools, or fatty diarrhea, often accompanied by abdominal pain. It is often associated with multiple endocrine neoplasia syndrome, such as hyperparathyroidism, diabetes, etc.

　　Physical examination revealed:Abdominal tenderness, fatigue, signs of endocrine tumors.

　　1. Abstain from long-term mental stress

　　Long-term mental stress can affect the autonomic nervous system through the cerebral cortex, causing vasoconstriction of the gastric mucosal blood vessels, disordered gastric function, excessive secretion of gastric acid and pepsin, leading to gastritis and ulcers. Clinically, those with long-term stress and anxiety, as well as depression, have a significantly higher incidence of gastric and duodenal ulcers.

　　2. Abstain from overexertion

　　Whether engaged in physical labor or intellectual labor, one cannot overwork, otherwise it will cause insufficient blood supply to the digestive organs, secretion disorder of the gastric mucosa, and lead to various stomach diseases.

　　3. Abstain from unbalanced diet

　　Unbalanced diet can cause great harm to the stomach. When hungry, the stomach is empty, and the gastric acid and pepsin secreted by the gastric mucosa are easy to harm the gastric wall, leading to acute or chronic gastritis or ulcers. Overeating can cause the gastric wall to overstretch, and food to stay in the stomach for too long, which is also easy to cause acute or chronic gastritis or ulcers, or even acute gastric dilatation and gastric perforation.

　　4. Abstain from excessive drinking

　　Alcohol can cause congestion, edema, and even erosion and bleeding of the gastric mucosa, forming ulcers. Long-term alcohol consumption also damages the liver, causing alcoholic cirrhosis, and the occurrence of pancreatitis is also related to excessive drinking. These damages can further worsen the injury to the stomach.

　　5. Abstain from the habit of smoking

　　Smoking can cause vasoconstriction of the gastric mucosal blood vessels, leading to a decrease in prostaglandin synthesis in the gastric mucosa. Prostaglandins are a protective factor for the gastric mucosa, and their reduction can cause damage to the gastric mucosa. Smoking also stimulates the secretion of gastric acid and pepsin, so being addicted to smoking is an important cause of various stomach diseases.

　　6, Six taboos of strong tea and coffee

　　Both strong tea and coffee are central stimulants that can cause the gastric mucosa to become congested, disrupt secretion function, and destroy the mucosal barrier through neural reflexes and direct effects, leading to the occurrence of ulcer disease. In addition, attention should be paid to the moderate consumption of foods that are strong in stimulating the stomach.

　　7, Seven taboos of eating in a hurry

　　Chewing slowly and thoroughly is conducive to the digestion of food. Eating in a hurry without sufficient chewing will inevitably increase the burden on the stomach. Studies have also found that when chewing slowly, the secretion of saliva increases, which plays a role in protecting the gastric mucosa and can avoid damage to the gastric mucosa from harmful substances.

　　8, Eight taboos of eating before going to bed

　　Eating before going to bed not only affects sleep but also stimulates the secretion of gastric acid, which is easy to induce ulcers.

　　9, Nine taboos of not maintaining hygiene

　　It has now been found that Helicobacter pylori infection is the culprit causing gastritis, ulcers, and gastric cancer. It can be transmitted through tableware, toothbrushes, kissing, and other means. Therefore, paying attention to hygiene, not using others' tableware and toothbrushes, can prevent Helicobacter pylori infection and thus prevent various stomach diseases.

　　10, Ten taboos of drug use

　　Many drugs can damage the gastric mucosa after long-term use, leading to erosive gastritis, hemorrhagic gastritis, and gastric ulcer. Among them, the commonly used drugs that can damage the gastric mucosa are divided into three categories: one is antipyretic and analgesic drugs such as aspirin, phenylbutazone, indomethacin, etc.; one is hormone drugs such as prednisone, dexamethasone; and the other is antibacterial drugs such as erythromycin, etc. Pay attention to strictly follow the doctor's advice and use these drugs cautiously to avoid causing damage to the stomach.

　　1, Gastric juice and gastric acid measurement:The total amount of gastric juice in 12 hours at night is more than 1000ml, about 66-90% of the patients have a basic acid output greater than 15mmol/h per hour, and about 50-67% of the patients have BAO/MAO greater than 60%.

　　2, Serum gastrin measurement:One-third of the patients often reach more than 1000pg/ml, about two-thirds of the patients are between 100-1000pg/L.

　　3, Secretin or calcium stimulation test:If it is 1-2 times or more than 500pg/ml before the experiment, it indicates gastrinoma.

　　4, Gastroscopy, X-ray barium meal examination:It can be found that there are ulcers, hypertrophy of mucosal folds, and much gastric juice, etc.

　　5, Tumor localization:It can be adopted by B-ultrasound, CT, MRI, angiography, and other methods.

　　In terms of diet, pay attention to eating more foods rich in protein and vitamins, and more fresh vegetables and fruits. Avoid overeating and irregular eating habits. Avoid eating cold, spicy, and刺激性 foods. Abstain from smoking and drinking alcohol, avoid drinking strong tea and coffee, and avoid lying down within half an hour after eating.

　　Pay attention to avoiding staying up late, avoiding fatigue, and avoiding too much emotional fluctuation.

　　The fundamental treatment for this disease is the resection of the tumor that produces gastrin. For those who cannot find the tumor or the tumor cannot be completely resected, drug treatment can be used.

　　Firstly, surgical treatment

　　1. Tumor resection:For gastrinomas that are solitary and without metastasis, it is generally recommended to perform surgical resection. However, tumors located within the pancreas can be completely resected and cured.

　　2. Total gastrectomy:In the past, it was believed that for patients with inoperable tumors or those with postoperative tumors, whose levels of gastric acid and serum gastrin could not decrease, a total gastrectomy could be performed to effectively cure peptic ulcers and there were also reports of regression of primary and metastatic tumors in a few patients. Considering that the mortality rate of total gastrectomy is as high as 5% to 27%, and there are many postoperative complications, it is gradually less used at present.

　　3. High-selective vagotomy of the gastric preganglionic nerve:It can significantly reduce the secretion of gastric acid, enhance the acid-suppressing effect of H2 receptor blockers, and reduce their drug dosage.

　　4. Removal of other endocrine tumors:For patients with parathyroid tumors, it is generally recommended to perform parathyroid tumor resection before abdominal surgery. After surgery, symptoms such as diarrhea and peptic ulcer can be alleviated, and the levels of gastric acid and serum gastrin decrease.

　　Secondly, drug treatment

　　1. Acid-suppressing drugs:After the introduction of H2 receptor blockers, the internal treatment of the disease has become possible. The dosage of H2 receptor blockers used by patients is larger than that of common peptic ulcer patients. Cimetidine 0.6g, Q4h. (Some patients may reach 5-10g/d); ranitidine 0.3g, Q8h. Famotidine 20mg, Q4h. To reduce the dosage of H2 receptor blockers, anticholinergic drugs can be used in synergy. Omeprazole and lansoprazole are proton pump inhibitors of parietal cells, which can strongly inhibit the secretion of gastric acid caused by various stimuli and are the most effective drugs for the treatment of the disease, with the former dose of 60mg, B.i.d.; and the latter of 60mg, Qid. Long-term treatment can be well tolerated. The dosage of acid-suppressing drugs should be individualized, and it is generally advocated to use BAO

　　2. Chemotherapy drugs:Applicable to patients with inoperable tumors and those with metastasis. Streptomycin has a therapeutic effect on tumors. Combination with 5-fluorouracil (5-Fu) is more effective when necessary. Currently, it is widely advocated to perform interventional treatment with streptomycin via catheterization of the celiac artery, which can reduce adverse reactions and increase efficacy.