Gastric fundus varices

　　The most common cause of esophageal-gastric varices is portal hypertension caused by liver cirrhosis. In addition, idiopathic portal hypertension, non-cirrhotic portal vein thrombosis, and Budd-Chiari syndrome are also common causes of portal hypertension-related esophageal-gastric varices. Studies have shown that nearly 50% of patients with liver cirrhosis will have esophageal-gastric varices, and their occurrence is related to the severity of liver disease. Only 40% of Child A patients have varices, while 85% of Child C patients do. Patients with primary biliary cirrhosis can develop varices and variceal bleeding in the early stages of the disease, even before cirrhosis has formed. 16% of patients with chronic hepatitis C and bridging fibrosis have esophageal varices.

　　Gastrointestinal bleeding, such as hematemesis and melena, is a common symptom in patients with liver cirrhosis. If there is significant gastrointestinal bleeding, the main source of bleeding is the rupture of varices and portal hypertension-related gastric disease. Varices are mainly esophageal-gastric varices, but they can also occur in other parts of the stomach or in any part of the intestines. Large and rapid blood loss can cause immediate hemodynamic changes, rapid decrease in blood volume, reduced return blood volume, decreased cardiac output, decreased blood pressure, decreased pulse pressure, increased heart rate, insufficient perfusion of organs and tissues throughout the body, oxygen deficiency, leading to functional and morphological damage, and more complex conditions. Large blood loss can reduce cerebral blood flow, causing the patient to become restless, indifferent, or unconscious. When cerebral blood flow decreases to 50%, these symptoms become very obvious, and hepatic encephalopathy may also occur.

　　Patients with portal hypertension often have three aspects of clinical manifestations:

　　1. Manifestations of the primary disease Portal hypertension is 90% caused by liver cirrhosis, and patients with liver cirrhosis often have fatigue, weakness, decreased appetite, weight loss, and 10% to 20% of patients have diarrhea. It can be seen that the skin is darkened to even black or mild jaundice, subcutaneous or mucosal hemorrhagic spots, spider veins, palm of the hand, splenomegaly, and manifestations of endocrine disorders, such as low libido, irregular menstruation (amenorrhea or excessive menstruation), and gynecomastia in men.

　　2. Manifestations of portal hypertension include ascites and edema, varicose veins in the abdominal wall and hemorrhoids, and splenomegaly.

　　3. Bleeding and its secondary effects Hemorrhage in patients with liver cirrhosis, such as gingival, subcutaneous, and mucosal bleeding, is a common symptom.

　　If there is significant gastrointestinal bleeding (vomiting blood and black stools), the main source of bleeding is the rupture of varicose veins and portal hypertension-related gastric disease. The varicose veins are mainly esophageal-gastric varices, but can also be found in other parts of the stomach or any part of the intestines. Rapid and massive blood loss can cause immediate hemodynamic changes, leading to a rapid decrease in blood volume, a decrease in return blood volume, a decrease in cardiac output, a decrease in blood pressure, a decrease in pulse compression, an increase in heart rate, insufficient perfusion of organs and tissues in the body, hypoxia, leading to functional and morphological damage, and the condition becomes more complex. After bleeding, through its own regulatory mechanism, sympathetic nerve excitation occurs first, causing vasoconstriction of the capacitance vessels and not causing obvious hemodynamic changes in blood circulation immediately; if bleeding continues, vasoconstriction of resistance vessels occurs, resulting in a decrease in peripheral skin temperature. However, the excitation of sympathetic nerves has no significant vasoconstrictive effect on the vessels of the viscera (heart, brain, etc.), which allows a larger amount of blood to be supplied to vital organs. When this compensatory mechanism cannot make the vascular bed adapt to the decrease in blood volume, the ventricular filling pressure decreases, the cardiac output decreases, the central venous pressure decreases, the heart rate accelerates, blood perfusion of organs and tissues is insufficient, and metabolic disorders occur accordingly, leading to the accumulation of acidic metabolic products. Resistance vessels cannot maintain their high tension, and they no longer respond to adrenergic stimulation, causing an increase in capillary permeability, fluid leakage, and further hemodynamic changes, leading to severe tissue damage. Therefore, arrhythmias, heart failure, and further deterioration of liver function may occur, and even jaundice, increased edema and ascites, and liver-kidney syndrome may occur. Patients may be restless, apathetic, or unconscious, which may be caused by a decrease in cerebral blood flow due to massive blood loss. When cerebral blood flow decreases to 50%, these phenomena become very obvious, and hepatic encephalopathy may also occur later.

　　Patients with blood loss, when they clench their fists and extend their palms, the wrinkles on the palm become pale, indicating a blood volume loss of 50%. If the patient shows shock while lying flat, the blood volume loss is about 50%; if shock occurs only when standing, the blood loss is about 20% to 30%. If the patient's head is elevated 75°, the blood pressure drops by 20 to 30 mmHg after 3 minutes, or if the blood pressure and heart rate of the patient when lying flat are compared with the results when standing, the blood pressure in the standing position decreases by 10 mmHg, and the heart rate increases by 20 beats/min, then the blood loss exceeds 1000ml. Therefore, the approximate amount of blood loss can be estimated based on clinical symptoms.

　　After massive hemorrhage, the spider angioma and palmar erythema may temporarily disappear, and the spleen may also shrink. After the circulatory function is restored after blood volume supplementation, they can recover.

　　Promptly collecting detailed medical history is very important for the diagnosis of hematemesis and melena. However, patients with acute massive hemorrhage often quickly enter a shock state and are unable to describe their medical history in detail. The medical history information provided by the caregivers may be incomplete and not necessarily reliable, so emergency treatment should be performed first, closely observed, and necessary examinations should be carried out at the right time. When the condition is relatively stable, the medical history should be inquired in detail and further examinations should be arranged.

　　Patients who have had hepatitis, especially those with recurrent abnormal liver function or transaminases; those who have been long-term carriers of hepatitis viruses, especially hepatitis B and C viruses; those who have received blood transfusions or blood products; those with a history of gallstones or chronic biliary tract infection; those with a history of schistosomiasis or contact with schistosome-infested water; those with long-term alcoholism; those with long-term medication or exposure to toxins; those with a history of abdominal trauma or surgery, should first consider the possibility of esophageal and gastric varices rupture bleeding.

　　Patients with liver cirrhosis without varices appear varices at a rate of 8% per year. The strongest predictor of varices in patients with liver cirrhosis who do not have varices at the time of endoscopic screening is HVPG > 10 mmHg. Patients with small varices develop into large varices at a rate of 8% per year. The annual incidence of variceal bleeding is 5%-15%, and the size of varices is the most important predictor of bleeding. The risk of the first bleeding for patients with large varices is the highest (15% per year). Other predictors of bleeding are decompensated liver cirrhosis (Child B/C) and red stripe sign under endoscopy. Patients with HVPG > 20 mmHg (measured within 24 hours of variceal bleeding) are considered to be at the highest risk of early recurrence (recurrence of bleeding within the first week of admission) or uncontrollable bleeding (83% vs. 29%) and have a higher one-year mortality rate (64% vs. 20%). Approximately 60% of untreated patients will have delayed recurrence, most of which occur within 1-2 years after the current bleeding.

　　1. The hepatic venous pressure gradient (HVPG) has predictive value for the development of esophageal and gastric varices, the risk of bleeding from varices, the occurrence of non-variceal complications of portal hypertension, and mortality. However, due to the invasive nature of HVPG measurement and the limitations of technology and equipment, it has not been widely implemented in China and is also difficult to popularize. But we suggest that HVPG detection should be performed for high-risk patients (patients with moderate to severe gastroesophageal varices, patients with a history of bleeding) as it is beneficial for the treatment and prognosis judgment of the patients. The HVPG of patients with liver cirrhosis and gastroesophageal varices should be at least 10-12 mmHg.

　　2. The golden standard for the diagnosis of varicose veins is esophageal-gastric duodenal endoscopy (EGD). There are two types of classification: one is based on the quantitative size of the truncation diameter: small varicose veins refer to those not exceeding 5mm, and large varicose veins refer to those exceeding 5mm. The second classification is divided into three types: small, medium, or large. It is mainly determined by semi-quantitative morphological assessment (small varicose veins are generally defined as veins with a lower degree of prominence on the esophageal mucosal surface, moderate varicose veins are defined as twisted veins occupying not more than 1/3 of the esophageal lumen, and large varicose veins are defined as twisted veins occupying more than 1/3 of the esophageal lumen).

      In addition to conventional treatment, attention should also be paid to diet in the treatment of gastric varices. Patients with this disease should pay attention to light diet, avoid the intake of spicy and刺激性 food, and at the same time, pay attention to staying away from greasy food.

　　The main treatment for esophageal-gastric varices is to prevent bleeding. Non-selective beta-blockers can prevent bleeding in more than half of patients with moderate or large varicose veins. Therefore, it is recommended that patients with liver cirrhosis undergo endoscopic screening for varices after diagnosis. For patients with compensatory liver cirrhosis without varices during screening endoscopy, EGD should be reviewed every 2-3 years, and for patients with small varicose veins, EGD should be reviewed every 1-2 years. For liver cirrhosis with decompensation, EGD should be reviewed annually.

　　EGD is expensive and often requires sedation. It can be avoided in patients with liver cirrhosis who are already taking non-selective beta receptor blockers for other reasons (such as hypertension). For patients who are already taking selective beta receptor blockers (such as metoprolol, atenolol) for other reasons, they need to be switched to non-selective beta receptor blockers (propranolol, nadolol). One method to replace EGD is esophageal capsule endoscopy. Recent two preliminary studies (pilot study) show that capsule endoscopy is a safe and well-tolerated method for diagnosing esophageal varices, although its sensitivity is yet to be determined. Therefore, if larger-scale studies support its use, capsule endoscopy may play an important role in the future screening of esophageal varices.

　　Beta-blockers for prevention should be used in patients with high bleeding risk and small varicose veins, that is, patients with advanced (progressive) liver disease and patients with red signs on varicose veins. Other patients with small varicose veins can receive beta-blockers to prevent the growth of varicose veins, although the long-term benefits are not yet fully determined. For those who choose not to use beta-blockers, experts recommend that endoscopy should be reviewed every 2 years, and if there is decompensation, it should be reviewed annually. The cost-effectiveness study of non-selective beta-blockers, sclerotherapy, and shunt surgery shows that beta-blockers are the only preventive treatment that meets the cost-effectiveness form.

　　Non-selective β-blockers (propranolol, nadolol) reduce portal pressure by reducing cardiac output (β1 effect), and more importantly, by producing visceral vasoconstriction (β2 effect) to reduce portal blood flow. Selective β-blockers (atenolol, metoprolol) are less effective and are not the best choice for primary prevention of variceal bleeding. In most of the published studies, the dose of β-blockers is gradually increased to reduce heart rate by 25% from baseline. However, because the measurement of HVPG is not always possible, and the reduction in heart rate is not associated with the reduction in HVPG, the dose of non-selective β-blockers (propranolol, nadolol) should be adjusted to the maximum tolerated dose. The usual starting dose of propranolol is 20mg, twice a day. Nadolol is usually 40mg, once a day. Because a randomized trial showed that the risk of bleeding recurrence will recur when β-blocker treatment is stopped, preventive treatment should be continued indefinitely. β-blockers are not suitable for patients with asthma, insulin-dependent diabetes (with hypoglycemic episodes) and peripheral vascular disease. The most common side effects of β-blockers are dizziness, fatigue, and shortness of breath.

　　The comparative study results on the endoscopic variceal ligation (ELV) and β-blockers in patients with high-risk varices (large varices with or without red spot) found that the incidence of the first variceal bleeding was low in the EVL group, and there was no difference in mortality. However, the adverse events in the EVL group were more serious, including esophageal ulcer bleeding caused by ligation and esophageal perforation caused by the sheath. Non-selective β-blockers combined with isosorbide mononitrate (ISMN) have a synergistic effect in reducing portal pressure. However, the recent two large-scale double-blind, placebo-controlled trials failed to confirm these beneficial results, and more side effects were observed in the combined treatment group. Therefore, it is not recommended to use β-blockers combined with ISMN for prophylactic treatment without more evidence of effectiveness.

　　The study on the prevention of the first variceal bleeding with the combination of non-selective β-blockers and EVL found that there was no difference between the two groups in terms of bleeding or mortality, although variceal recurrence was more common in the EVL group alone, but more side effects were observed in the EVL+propranolol group. Therefore, it is not recommended to use the combination at present.