Infant and toddler gastroesophageal reflux

　　1. Etiology

　　In the past, it was believed that the lower esophageal sphincter (cardiac sphincter) was the only anatomical structure to prevent the reflux of stomach contents. However, it is now considered that GER is not solely caused by the dysfunction of the lower esophageal sphincter, but is a result of the combined effects of many factors. Among them, the lower esophageal sphincter is the primary anti-reflux barrier. The normal peristalsis of the esophagus, the mucosal flap at the end of the esophagus, the crural esophageal ligament, the length of the abdominal esophagus, the clamping effect of the diaphragmatic crura, and the His angle also play a certain role in preventing reflux. If any of these anatomical structures are altered in terms of structure or function, stomach contents can reflux into the esophagus, leading to esophagitis.

　　1. The first anti-reflux barrier - lower esophageal sphincter. In the early 1980s, most scholars believed that the lower esophageal sphincter did not actually exist anatomically and was merely a functional term. In recent years, with the deepening of ultra-microscopic anatomical research, it has been suggested that such a muscle structure indeed exists. The maturation of fetal esophageal function occurs from the end of pregnancy to the first week after birth. The lower esophageal sphincter is located at the junction of the esophagus and stomach, and the corresponding esophageal mucosa has thickening changes, forming a 'Z' line, which also plays a certain role in anti-reflux. The lower esophageal sphincter pressure (LESP) can increase due to vagal nerve excitation. After a long-term study, it has been observed that certain hormones can affect the lower esophageal sphincter pressure.

　　The high-pressure zone formed by the lower esophageal sphincter is the most effective anti-reflux barrier. When the intragastric pressure increases, the lower esophageal sphincter responds with active contraction, which can exceed the increased intragastric pressure.

　　Children with reduced lower esophageal sphincter pressure are prone to gastroesophageal reflux through the low-tension lower esophageal sphincter. The current standard for gastroesophageal reflux is that the stomach contents reflux into the lower esophagus, with each cycle lasting more than 15 seconds, and the pH dropping below 4 (the normal pH of the lower esophagus is 5-7). However, some experiments have proven that some infants with normal lower esophageal sphincter pressure can also have gastroesophageal reflux, indicating that the measurement of lower esophageal sphincter pressure alone cannot fully reflect the clinical differences.

　　2. The second barrier - normal esophageal peristalsis Normal esophageal peristalsis plays an effective esophageal clearance role, that is, it produces primary peristalsis reflexively, transporting food into the stomach. Sometimes food may reflux from the stomach to the esophagus, and if the esophageal function is good, the upper part of the esophagus can produce secondary peristalsis, quickly sending the refluxed food back into the stomach. Normally, the esophagus effectively clears through peristalsis, but in some pathologic gastroesophageal reflux cases, it is often observed that the amplitude of esophageal peristalsis is low, and the acid resistance of the esophageal mucosa is weakened. If secondary peristalsis is weakened or disappears, the contents of the stomach can reflux upwards through the mouth. Esophagitis often affects the peristaltic ability of the esophagus, extending the time for clearing acidic contents.

　　3. The resistance of the esophageal mucosa After the contents of the stomach reflux into the esophagus, the mucosal epithelium of the esophagus does not necessarily come into contact with it immediately, because the pre-epithelial defense mechanism - the luminal mucus layer, hydrostatic layer, and mucosal surface HCO-3 can play a physical and chemical barrier role. The esophageal mucosa is susceptible to damage from acid, pepsin, or bile acids, and when in contact with these substances, the mucosal potential difference is easily altered, and the protective layer is destroyed. Animal experiments and clinical observations have proven that esophageal mucosal damage is most likely to occur during gastroesophageal reflux.

　　4. The length of the esophageal segment in the abdominal cavity and the His angle The esophageal segment in the abdominal cavity and the His angle are a soft digestive tract, and when the intraperitoneal pressure increases, the abdominal esophageal segment is clamped into an oblong shape. The ratio of the esophagus to the effective diameter of the stomach is 1:5. The abdominal esophageal segment only needs to exceed the intragastric pressure by 1/5 to close. The longer the esophageal segment in the abdominal cavity, the more perfect its function becomes. Infants younger than 3 months have a very short abdominal esophageal segment, so they are more prone to gastroesophageal reflux.

　　The gastroesophageal angle, also known as the His angle, is normally acute and acts as a barrier against reflux, forming after one month of birth. When esophageal hiatus hernia occurs, the angle in most cases becomes obtuse. This angle also depends on the length of the esophagus in the abdominal cavity.

　　5. It has been reported that a high proportion of infants with gastroesophageal reflux have delayed gastric emptying, which also explains why reflux occurs more often after eating. Changes in gastric emptying, expansion, and the volume of gastric contents can all affect gastroesophageal reflux. Studies have also confirmed that normal newborns do not develop normal gastric peristalsis until 12 weeks after birth, and maturation takes time, which affects gastric emptying and increases the risk of gastroesophageal reflux. The lower part of the stomach has peristaltic points, and when esophageal hiatus hernia occurs, the lower part of the stomach often enters the thoracic cavity, affecting the stomach's role in emptying liquids and causing reflux. In addition, a lack of coordination between peristaltic waves and pyloric opening can also affect gastric emptying. It is worth noting that the stomach, affected by invasive factors, often triggers or exacerbates gastroesophageal reflux. For example, recent reports indicate that children with Zollinger-Ellison syndrome have increased gastric acid secretion, which also significantly increases the incidence of gastroesophageal reflux. Reflux esophagitis, and pepsin in duodenal contents also have a damaging effect on the lower esophageal mucosa.

　　In addition, some recent concerns about anti-reflux mechanisms, such as the spring clip-like action of the diaphragm esophageal hiatus and the diaphragm esophageal membrane. Such mechanisms, as mentioned above, collectively form the normal anti-gastroesophageal reflux action.

　　Secondly, Pathogenesis

　　1. Factors affecting the degree of damage: The degree of mucosal damage in reflux esophagitis depends on three factors: ① The special action of the reflux material; ② The duration of contact with the reflux material; ③ The esophagus's ability to clear the reflux material.

　　2. Pathological morphology: Since esophagitis is at different stages of development, the degree of lesion is not the same as the corresponding pathological morphological characteristics. It can usually be divided into early stage (mild lesion phase), middle stage (progression of inflammation and formation of erosion), and late stage (chronic ulcer formation and inflammatory hyperplasia).

　　(1) Mild lesion phase: The main histological change is the hyperplasia of the basal cells in the epithelial layer, with an increase in thickness. The ratio of thickness between the superficial epithelium and the basal layer has changed; the papillae of the lamina propria extend upwards to the epithelial layer.

　　(2) Progression of inflammation and formation of erosion: Histological examination shows that the epidermal cells in the lesion area die and fall off, forming superficial epithelial defects. The defects are covered by an inflammatory fibrinous membrane, below which neutrophils and lymphocytes can be seen, with plasma cell infiltration. The inflammatory changes are mainly limited to the submucosal layer above the mucosal muscle layer. Superficial capillaries and fibroblast hyperplasia can also be seen, forming chronic inflammatory or healing granulation tissue.

　　3. Ulcer formation and inflammatory hyperplasia: Esophageal ulcers during the inflammatory hyperplasia phase appear as solitary or confluent, annular. The histological changes are that the ulcer extends from the mucosal layer to the submucosal layer, rarely involving the muscular layer. The lesion tissue at the ulcer site shows a stratified structure, with the surface being an exudative fibrinous material, below which is necrotic tissue. Below the necrotic tissue, there is granulation tissue composed of new capillaries, proliferating fibroblasts, chronic inflammatory cells, or a mixture of an unequal number of neutrophils. The bottom is scar tissue formed by granulation tissue.

　　1. Esophageal Stricture:Prolonged and repeated gastroesophageal reflux can cause esophagitis, which can be observed during esophagogastroduodenoscopy as hyperemia, edema, erosion, ulceration, and hyperplasia of fibrous tissue. This can lead to scar formation, resulting in esophageal stricture or even shortening. Reports indicate that 8% to 20% of reflux esophagitis may develop into esophageal stricture, with clinical manifestations such as difficulty in swallowing, changes in the texture of food, such as choking when eating solid food, preference for soft or liquid food, and in severe cases, vomiting can occur even with slightly faster eating speed.

　　2, Bleeding and perforation:Reflux esophagitis, due to mucosal congestion and erosion, can cause slight bleeding. In the long term, it can lead to varying degrees of iron deficiency anemia in children. In a few severe cases, due to esophageal ulcers, a larger amount of bleeding or even perforation can occur.

　　3, Barrett's esophagus:It is a severe complication of chronic gastroesophageal reflux. Normally, the squamous epithelium at the lower end of the esophagus intersects with the columnar mucosal columnar epithelium of the cardia, forming a dentate line (Z-line). As a consequence of chronic reflux esophagitis, the lower segment of the esophagus shows a columnar epithelial area, while the normal squamous epithelial area is destroyed and replaced by the adjacent area or gland duct columnar epithelium with stronger regeneration, forming Barrett's epithelium. The metaplastic epithelium has the epithelium of the stomach, small intestine, and colon, and is histologically similar to mucous cells, goblet cells, and villous structures. The clinical manifestation is typical reflux symptoms, and the incidence of esophageal adenocarcinoma in adults with Barrett's esophagus is 30 to 50 times higher than that in the general population.

　　The clinical manifestations of pediatric gastroesophageal reflux vary in severity and are mainly related to the intensity, duration, presence of complications, and age of the child. Gastroesophageal reflux in children usually presents with the following four manifestations.

　　1, Symptoms caused by reflux itself:The main manifestations are vomiting, with vomiting after feeding being a typical symptom. About 85% of children experience vomiting within the first week of life. 65% of children can spontaneously relieve symptoms within half a year to a year without clinical treatment, actually belonging to the category of physiological reflux. Clinical treatment is not required for this group, and only a few children present with recurrent vomiting that gradually worsens, which can lead to malnutrition and delayed growth and development. Older children may have symptoms such as acid regurgitation and hiccups.

　　2, Symptoms caused by the stimulation of refluxed material to the esophagus:Due to the presence of a large number of aggressive factors in the contents of the stomach or duodenum, damage to the esophageal mucosa can occur. Older children may present with symptoms such as heartburn, pain behind the sternum, and dysphagia. Severe esophageal lesions can manifest as reflux esophagitis, leading to hematemesis or vomiting coffee-like material. Such children often have anemia. The symptoms of reflux esophagitis that persist can further lead to complications such as esophageal stricture and Barrett's esophagus.

　　3, Symptoms other than esophageal stimulation:In recent years, the most attention has been paid to the causal relationship between gastroesophageal reflux and recurrent respiratory tract infections. About 1/3 of children experience recurrent coughing, asthma, bronchitis, and respiratory tract infections such as aspiration pneumonia due to aspiration of refluxed material. Asthma caused by reflux is not seasonal and often occurs at night. Recurrent aspiration pneumonia can lead to pulmonary interstitial fibrosis. In newborns, reflux can cause sudden asphyxiation or even death. In a few cases, it can manifest as Sandifer syndrome, characterized by a special 'rooster head' posture during an attack, accompanied by heartburn, clubbing, hypoproteinemia, anemia, and in some cases, even oral ulcers and dental diseases, leading to visits to the stomatological department while the reflux symptoms are not obvious or ignored. Esophagogastroduodenoscopy may lack the manifestation of esophagitis, and after anti-reflux treatment, oral ulcers can be alleviated or healed.

　　The manifestations of pediatric gastroesophageal reflux vary in severity, and a considerable number of gastroesophageal refluxes are physiological phenomena. The manifestations of gastroesophageal reflux in children of different ages are not the same, so it is very important to objectively and accurately determine the reflux and its nature.

　　1. Abstain from smoking and drinking:Smoking is the primary measure to prevent laryngeal cancer. Tobacco is the king of spicy and hot, and alcohol is the most damp and hot. Smoking and drinking are extremely harmful to the throat.

　　2. Light diet:All kinds of ginger, pepper, mustard, garlic, and other spicy and hot foods can harm the mucosa of the throat. These spicy and fried foods should be avoided, and more fruits and vegetables rich in vitamin C should be eaten.

　　3. Pay attention to oral hygiene:Pay attention to personal hygiene, wash hands frequently. In the morning and evening, you can gargle with weak saltwater, and it is not advisable to drink a glass of weak saltwater after gargling. This can clean and moisten the throat, improve the throat environment, and prevent bacterial infection.

　　One, Esophageal Barium Meal Contrast Imaging

　　The main X-ray manifestations of early and mild reflux esophagitis are functional changes of the esophagus and slight morphological changes of the mucosa. The esophageal spasm caused by inflammation can often be seen as a slight narrowing of a few centimeters at the lower end of the esophagus during barium meal examination, with a small amount of barium retention above it, which can still pass through. The narrow segment can expand to a normal degree, and the narrowing reappears after the barium passes through. During upright examination, although the barium can pass through the esophagus, the emptying time is delayed compared to normal. After lying down and taking a barium meal, the normal esophageal peristalsis stops at the level of the aortic arch, and although the barium can enter the lower esophagus, it is usually only in the second swallowing of barium that a small amount of barium enters the stomach.

　　The degree of gastroesophageal reflux seen on X-rays is not parallel to the severity of reflux esophagitis. In the early and mild stages of reflux esophagitis, the X-ray examination shows rough mucosal surfaces and lumen wall lines; the mucosal surface may appear as needle-tipped barium spots or granular small nodular shadows; sometimes erosive foci can be seen, presenting as small spot-like barium spots; or reticulated intersecting linear shadow can be observed, in addition, there may be wider transverse folds in the esophagus, which are often located near the narrowing or deformation of the esophagus.

　　When scar cicatricial stricture forms, its shape is often tubular or funnel-shaped, the narrow segment is usually regular, with smooth or rough edges, showing serrated shapes. The narrow segment is often stretched, straightened, losing its normal curvature, with reduced expansion. The esophageal lumen above the narrow segment is slightly expanded, and ulcers are often visible at the lower end of the esophagus, presenting as clear, roundish shadow of small foci with a clear boundary, generally shallow.

　　Esophageal imaging also has a certain diagnostic value for the degree of damage to esophagitis. McCauley has established a classification table for X-ray images of gastroesophageal reflux, which is helpful in distinguishing the degree of gastroesophageal reflux.

　　X-ray classification of gastroesophageal reflux: 0 level: no gastric contents reflux into the lower end of the esophagus; Level I: small amount of gastric contents reflux into the lower end of the esophagus; Level II: reflux mainly in the esophagus, equivalent to the level of the aortic arch; Level III: reflux mainly in the pharynx; Level IV: frequent reflux mainly in the pharynx, accompanied by esophageal motility disorders; Level V: reflux mainly in the pharynx, with barium aspiration.

　　The positive rate of X-ray diagnosis of gastroesophageal reflux is only 25% to 75%, and Meyers et al. reported a false-negative rate of 14% and a false-positive rate as high as 31%. This is related to the amount of barium swallow during the examination, especially in newborns.

　　During X-ray examination, attention should also be paid to whether there is a hiatus hernia, especially the sliding type. This type of hernia shows an enlarged esophageal gastroesophageal vestibule on X-ray, with part of the gastric mucosa located above the diaphragm and an ascending esophageal-gastric ring visible.

　　Two, esophageal dynamics examination

　　In 1957, Colley et al. in the United States first performed esophageal pressure measurement in the study of achalasia. In 1959, Chappell introduced this technique to Europe, studying the motility disorders of megaesophagus. In 1961, Euler used pressure measurement to study the function of the cardia. Subsequently, Bettex, Cargill, and others have successively reported on the pressure measurement of hiatus hernia, gastroesophageal reflux, and so on. Esophageal pressure measurement has now become a widely used technique for monitoring esophageal function, evaluating diagnosis and treatment.

　　In the diagnosis of gastroesophageal reflux, the main focus is on the esophageal motility and the function of the lower esophageal sphincter. The examination is safe, simple, and non-invasive. Newborns within 6 days of birth have significantly lower lower esophageal sphincter pressure, but this gradually approaches the values of older age groups as age increases.

　　In recent years, a large number of reports have shown that newborns or infants with gastroesophageal reflux have varying degrees of decreased lower esophageal sphincter pressure, with a shorter length of the lower esophageal sphincter pressure area than that of normal age-matched groups and poor lower esophageal sphincter compliance. However, a portion of newborns and infants with gastroesophageal reflux have normal lower esophageal sphincter pressure, while normal children without gastroesophageal reflux show a low lower esophageal sphincter pressure. The coincidence rate between the decrease in lower esophageal sphincter pressure and the occurrence of gastroesophageal reflux is about 87%.

　　Three, 24h esophageal pH monitoring

　　In 1969, Spencer first described it, and it was further developed by DeMeester and Johnson. The sensitivity of 24h esophageal pH monitoring in the diagnosis of gastroesophageal reflux is 88%, and the specificity is 95%. It is currently the preferred diagnostic method, which can objectively reflect the reflux situation, is safe, easy to operate, and can distinguish physiological from pathological reflux.

　　Under normal circumstances, there is no reflux during sleep, the total reflux time is less than 4% of the monitoring time, the average duration of reflux is less than 5 minutes, and the average clearance time is less than 15 minutes. Experience from Shanghai Xinhua Hospital with 102 children's 24-hour esophageal pH monitoring shows that this is a new technology with high accuracy, safety, and no injury.

　　Fourth, esophageal endoscopy

　　This is the most suitable method for determining esophagitis, combined with pathological examination, which can reflect the severity of esophagitis with a sensitivity of 95% and specificity of 41%. However, this method cannot reflect the severity of reflux, only the severity of esophagitis. It is difficult to judge mild (Grade I) esophagitis, so most scholars propose that mucosal biopsy is not necessary for esophagitis of Grades I or II, only Rubin tube aspiration biopsy is performed when the endoscopy is not clear or there are suspicious changes. In principle, no biopsy is performed in the neonatal period. Mucosal biopsy is also the main basis for diagnosing Barrett's esophagus. The classification of reflux esophagitis under endoscopy:

　　1, Savary-Miller classification (1978):I: Isolated erosion foci and erythema foci and/or exudation; II: Scattered erosions and ulcers, not involving the entire circumference of the esophagus; III: Erosions and ulcers involving the entire circumference of the esophagus but not forming stenosis; IV: Chronic lesions or ulcers, with fibrosis, stenosis, short esophagus, and/or columnar epithelial esophagus.

　　2, Jamieson classification:

　　0: Normal mucosa; I: Isolated erythema area; II: Ulcer formation; III: Formation of esophageal stenosis.

　　3, Classification of the 9th World Gastroenterology Conference:I: Sparse, vertical erosions or ulcers; II: Fused ulcers; III: Ulcers fused into a ring shape; IV: Scars, stenosis.

　　Fifth, nuclear scintigraphy recording of gastroesophageal reflux

　　Inject 99mTc labeled solution into the gastric tube, and then perform a scintigraphy scan in a quiet state to record. This examination can provide information on whether there is gastroesophageal reflux, and observe the function of the esophagus, and can take continuous films at the same time, understanding the function of gastric emptying, esophageal clearance, and so on. When labeled radionuclides appear in the lungs, it can be confirmed that respiratory symptoms are related to gastroesophageal reflux. Rudd suggests that this method has a sensitivity of 80% in diagnosing pediatric gastroesophageal reflux.

　　Sixth, acid reflux test (Tuttle test)

Insert a pH microelectrode probe about 3cm above the lower esophageal sphincter, and then inject 300ml of 0.1mol/L hydrochloric acid solution, calculated according to the body surface area per 1.73m2, through a nasogastric tube into the stomach. Monitor the esophageal pH, and when there is gastroesophageal reflux, the pH is less than 4. This test has a high sensitivity and does not cause too much stimulation to the child. Some people have found that apple juice can substitute for the hydrochloric acid solution with similar effects, and some authors believe that the false positive rate can reach 31%, which is not as good as the 24-hour pH monitoring, which is non-invasive and highly accurate.

　　All of the above methods have some shortcomings. In recent years, Arasu, Bettex, and others have successively proposed that the combined application of 2 measurement methods can better indicate the accuracy of diagnosis. Currently, the most commonly used methods are X-ray esophageal barium swallow, esophageal dynamical examination, and 24-hour esophageal pH monitoring.

　　1. Vitamin C supplementation:Vitamin C has a protective effect on the stomach, maintaining normal levels of vitamin C in the gastric juice can effectively exert the function of the stomach, protect the stomach, and enhance the stomach's resistance to diseases. Therefore, it is advisable to consume more vegetables and fruits rich in vitamin C.

　　2. Gastroesophageal reflux:The main reason is that the lower esophagus cannot function properly, causing gastric juice to reflux into the esophagus. Foods that these patients should not consume include chocolate, coffee, spicy foods, mint, citrus, tomatoes, whole milk, and onions, while foods that can be consumed include high-protein foods (poultry eggs), fibrous foods (vegetables, grains), and easily digestible rice congee.

　　3. Functional dyspepsia:In daily life, it is advisable to consume light foods and drinks such as fresh fruit juice, oatmeal, and millet congee in moderation.

　　4. Gastric or duodenal ulcer:For gastric diseases, it is advisable to consume easily digestible and nutritious foods such as grains, soy milk, tofu, eggs, fish, tender lean meat, animal liver, etc., to reduce the irritation of gastric acid on the gastrointestinal mucosa.

　　First, treatment

　　1. Surgical treatment

　　(1)Indications and contraindications: Only 5% to 10% of children with gastroesophageal reflux require surgical treatment, so the indications for surgery should be carefully selected. The following situations are indications for anti-reflux surgery: ①Failure of medical treatment or recurrence soon after stopping medication; ②Gastroesophageal reflux caused by congenital diaphragmatic hernia; ③Severe reflux complications, such as esophagitis with bleeding, ulcers, stricture, etc.; ④Recurrent respiratory infections and asphyxia caused by reflux; ⑤Objective evidence of pathological reflux (such as dynamic pH monitoring); ⑥Alkaline gastroesophageal reflux.

　　Cases requiring cautious consideration for anti-reflux surgery include: ①Insufficient medical treatment: including posture therapy, dietary adjustment, and taking acid-suppressing agents after meals and before bedtime. If after at least 6 weeks of treatment, the reflux symptoms still persist, consider performing a radioactive isotope examination of gastric emptying. If there is a gastric emptying disorder, additional gastric motility drugs can be used. If symptoms cannot be controlled even after this, further consideration should be given to surgical treatment. For effective treatment of gastroesophageal reflux and its complications, it is best for pediatric gastroenterologists and pediatric surgeons to collaborate in formulating a comprehensive treatment plan. ②Gastroesophageal reflux in the neonatal period and in small infants: The vast majority of gastroesophageal reflux occurring during this period is physiological and gradually resolves and heals with age. A small number of pathological gastroesophageal reflux can also be effectively treated with medical treatment, so surgery should be chosen with great caution. ③Lack of objective evidence of reflux disease: Such as recurrent upper respiratory tract infections, asphyxia, which cannot be definitely attributed to reflux, should not be treated surgically without hesitation. Otherwise, it may expand the surgical indications and lead to adverse treatment outcomes.

　　(2) Surgical principles: Anti-reflux surgery is achieved through the anatomical reconstruction of the fundus and cardia, restoring its normal closing ability to prevent reflux, which means it can be normally swallowed and also can vomit when necessary. The basic principles of anti-reflux surgery are: ① Increase the resting pressure of the lower esophageal sphincter: generally restore to twice the level of the resting pressure of the stomach to maintain a positive pressure barrier between the esophagus and stomach, usually achieved by wrapping the fundus around the distal esophagus. Relevant data indicates that the degree of fundoplication is proportional to the increase in sphincter pressure, with the Nissen 360° fundoplication showing the most significant pressure increase after surgery. ② Maintain a sufficient length of the abdominal segment of the esophagus: The abdominal segment of the esophagus is in an intraperitoneal positive pressure environment. During the operation, the abdominal segment of the esophagus should be freed up by 1.5 to 2.0 cm to maintain the closing state of the cardia. Clinically, whether it is Nissen, Belsey, or Hill surgery, the average length of the abdominal segment of the esophagus can be increased by about 1 cm. ③ The reconstructed cardia should be able to relax during swallowing: Under physiological conditions, swallowing is facilitated by the vagus nerve, causing the lower esophageal sphincter and the fundus to relax for about 10 seconds, and then quickly recover the tension before swallowing. Attention should be paid to protect the neural supply of the cardia during the operation, prevent injury to the vagus nerve, otherwise it may lead to relaxation of the cardia and loss of tension.

　　(3) Common surgical methods:

　　①Nissen surgery: Also known as 360° fundoplication, it is a commonly used anti-reflux surgery in clinical practice. The typical Nissen surgery involves an incision below the left rib, but the clinical practice often uses a median upper abdominal incision. After entering the abdomen, the left triangular ligament is cut, the left lobe of the liver is pulled to the right, and the abdominal segment of the esophagus is exposed. The retroperitoneum in front of it is incised, the phrenoesophageal membrane is incised, and a sufficient length of the abdominal segment of the esophagus is freed up, wrapped around with gauze. Then, the fundus of the stomach is freed up, the upper part of the gastrohepatic ligament is incised on the lesser curvature side, the splenic ligament is incised on the greater curvature side, and the short gastric vessels are transected. The free fundus should reach a state without tension after folding and suturing. Pay attention to protect the vagus nerve during the free process. The posterior wall of the freed fundus is pulled to the right behind the esophageal orifice, where it meets the anterior wall of the displaced stomach in front of the lower end of the esophagus, completing the circumferential wrapping of the fundus around the esophagogastric junction. Then, the fundus is folded and sutured; the folded fundus should not be sutured too tightly, and the suturing part should pass through the surgeon's index finger. The left and right crura of the diaphragm are sutured behind the esophagus to narrow the diaphragmatic hiatus. After suturing is complete, the esophagus beside it can accommodate the surgeon's index finger through the hiatus.

　　In fact, after the improvement of many authors, the Nissen fundoplication has included a variety of different surgical methods, and the trend is to strive for a shorter fundoplication suture. DeMeester advocates a single-stitch fundoplication to reduce swallowing difficulties and gas bloat syndrome (GBS). Other improved methods include partial fundoplication with reduced fundoplication degrees (less than 360°).

　　In addition, Nissen surgery can be combined with other surgeries to treat some complex gastroesophageal reflux patients. For example, Collis-Nissen surgery can be used for patients with short esophagus; Thal-Nissen for peptic esophageal stricture; for achalasia, perform esophageal muscular layer incision at the same time as total fundoplication, and there are still controversies about the postoperative results and method evaluation of these surgeries.

　　In summary, Nissen surgery can have the following aspects: A. Increase the pressure of the lower esophageal sphincter to form an effective esophageal-gastric anti-reflux positive pressure barrier. B. Increase the length of the abdominal esophagus, fully maintain the closure state of the esophageal orifice. C. The folded stomach acts as a valve, allowing the esophageal contents to pass in one direction; D. Constrict the esophageal hiatus.

　　According to a large number of literature reports, the cure rate of Nissen surgery can reach 88%, and 90% to 96% of patients have symptoms relief after surgery. The dynamic pH monitoring of 13 and 9 cases of gastroesophageal reflux surgery by DeMeester and Goodill showed that the acidic reflux index was restored to the normal range.

　　Nissen surgery is generally performed through the abdominal approach. The following situations should consider thoracic surgery: A. Repeat surgery for failed anti-reflux surgery; B. Accompanied by short esophagus; C. Lesions in the chest need to be treated, such as esophageal ulcer or diaphragmatic hernia, etc.

　　Belsey Mark IV surgery: a 240° partial anterior gastrectomy, the advantages of which are: A. Freely mobilize the lower esophagus to restore the lower esophageal sphincter to a longer high-pressure zone; B. Adequate exposure through the left thoracic approach; C. Particularly suitable for patients with severe esophagitis, esophageal motility disorders, and recurrent gastroesophageal reflux. Its disadvantages are that the muscle fibers of the esophageal wall are thin, and there is a possibility of cutting and tearing after suture. In addition, whether the partial fundoplication can effectively prevent reflux is still controversial.

　　③Hill surgery: Transabdominal posterior gastric fixation (transabdominal posterior gastropexy), commonly used for repairing hiatal hernia. The surgical principle is: A. Restore the length of the abdominal esophagus; B. Increase the angle between the stomach and esophagus (His angle); C. Tighten the esophageal lower sphincter sling fibers to strengthen the function of the lower esophageal sphincter; D. Narrow the diaphragmatic hiatus.

　　(4) Evaluation of surgical efficacy: The evaluation of the efficacy of anti-reflux surgery can be referred to the following indicators: ① Complete elimination of gastroesophageal reflux symptoms and complications; ② Ability to belch and expel excess gas in the stomach; ③ Nausea can occur when necessary; ④ Objective examination of gastroesophageal reflux, such as 24-hour dynamic pH monitoring, esophageal-gastric motility examination, etc., restored or close to normal range.

　　2. General treatment

　　In the treatment of gastroesophageal reflux in children, especially neonates and infants, posture and dietary feeding are very important.

　　(1) Prone position with the head tilted forward: The optimal position for the child is prone with the head tilted forward by 30° (including sleep time). Meyers and Herbst have successively confirmed that this position has the advantage that the esophagus-gastric junction is located at the top, reducing contact with acidic substances. It is more conducive to gastric emptying and reducing reflux than the right lateral sleeping position or the upper body elevated position. Orenstein et al. have confirmed through observation that the commonly used position therapy (conventional >45° or sitting up) actually promotes the exacerbation of gastroesophageal reflux, and the number of reflux episodes in the Jolly chair sitting position is 4 times that of the prone position with the head tilted forward by 30°.

　　(2) High-protein, low-fat diet: Physiological gastroesophageal reflux during sleep is very rare, most occurring within 2 hours after meals. Therefore, feeding can be done with thick, sticky paste-like foods, with small portions and frequent meals, mainly high-protein, low-fat meals to improve symptoms or reduce the frequency of vomiting. It is not advisable to drink beverages after dinner to avoid reflux, and it is best to avoid using spicy seasonings and foods or drugs that affect the lower esophageal sphincter tone.

　　3. Drug treatment

　　In the past 10 years, there has been rapid development, mainly involving two categories of drugs: prokinetics and acid inhibitors. Their combined use is more effective for reflux esophagitis. There is a wealth of experience in the treatment of gastroesophageal reflux in adults and older children, but at present, it is only in the observation and trial study stage in the neonatal period, so caution should be exercised when applying it to the latter.

　　(1) Prokinetic drugs:

　　①Bethanechol (Carbamylmethylcholine): A parasympathomimetic drug that increases the lower esophageal sphincter tone, reduces gastroesophageal reflux, and also enhances the amplitude of esophageal contraction, with the effect of clearing acidic substances and promoting gastric emptying. The pediatric dose is 8.7mg/m2 of body surface area. The main side effects are abdominal cramps, diarrhea, frequent urination, and blurred vision, but the side effects are mild and transient. Asthma is a relative contraindication to the drug.

　　②Metoclopramide: A peripheral and central nervous system dopamine receptor antagonist that can promote the release of acetylcholine from postganglionic nerve endings, increase the amplitude of esophageal contraction and the tension of the lower esophageal sphincter, promote gastric emptying, and has no effect on gastric acid secretion. The pediatric dose is 0.1mg/kg per dose, 3-4 times a day. However, long-term use can cause serious side effects, with about 1/3 of children developing neurological and mental symptoms such as anxiety, restlessness, insomnia, and acute extrapyramidal symptoms, which often force discontinuation of the drug. Long-term use of the drug is not ideal in clinical practice.

　　③Domperidone (Domperidone, Metoclopramide): Its antiemetic and gastrointestinal motility effects are based on its antagonism of dopamine receptors, affecting gastrointestinal motility. Due to poor penetration of the blood-brain barrier, it has almost no inhibitory effect on dopamine receptors in the brain, so it can exclude mental and neurological side effects. This drug can restore the peristalsis and tension of the upper gastrointestinal tract, promote gastric emptying, increase the motility of the antrum and duodenum, coordinate the contraction of the pylorus, and can also enhance the peristalsis and tension of the lower esophageal sphincter. The pediatric dose is 0.3mg/kg per dose, 3-4 times a day. Side effects are rare, and only occasional mild transient abdominal cramps and observable increase in serum prolactin levels can be observed, which can return to normal after discontinuation of the drug. When taking this drug, attention should also be paid to the fact that the use of anticholinergic drugs may weaken the drug effect. In addition, due to the incomplete development of metabolism and blood-brain barrier function in children under 1 year of age, great care should be taken when administering drugs to infants.

　　④Cisapride: A new and effective esophageal and gastrointestinal motility drug. It can increase gastric emptying and lower esophageal sphincter pressure, part of whose action is similar to cholinergic mechanisms, including the release of acetylcholine from the interstitial ganglion, which has no effect on gastric acid secretion and does not increase esophageal peristalsis. Its action range is wide, and it can improve the motor function of the entire digestive tract. The pediatric dose is 0.3mg/kg, three times a day. For infants from 5 days to 11 months old, the dose can be 0.15-0.2mg/kg, three times a day. It is reported that after taking the drug for 3-7 days, the reflux can be significantly improved. If combined with bronchopulmonary lesions, after taking the drug, not only the reflux can disappear, but also the symptoms of the lungs can be improved or disappear within a few weeks. The drug has few side effects, and only a few children may experience transient abdominal rumbling and loose stools, which are due to increased gastrointestinal motility.

　　(2) Antacid drugs:

　　①Cimetidine (Cimetidine, Nizatidine): An H2 histamine receptor antagonist, this drug is effective in reducing gastric acid secretion. In recent years, Cucchiara reported that the use of this drug in combination with antacid therapy for gastroesophageal reflux disease is relatively effective. The pediatric dose is 20-40mg/kg per day. The side effects are few. Generally, serious adverse reactions have not been found. There may be mild elevation of blood creatinine or serum transaminase, which can return to normal after discontinuation of the drug. A few patients who have taken the drug for a long time may develop breast development in males, and sometimes headaches, constipation, and diarrhea, which generally do not affect treatment. Occasionally, drug fever and rash may occur, and patients with reduced gastric function should reduce the dose accordingly.

　　② Ranitidine: It acts quickly and is an effective histamine H2 receptor antagonist. Its action is stronger than that of cimetidine, and it can inhibit the induced gastric acid secretion, that is, reduce its secretion volume and also reduce the acidity and pepsin content. Although it has no effect on increasing the lower esophageal sphincter tension, it is effective in treating gastroesophageal reflux disease. The pediatric dose is 5-10mg/kg. Adverse reactions are rare, and there have been no serious adverse reaction reports in foreign applications for many years. A few children (7% to 8%) may experience fatigue, headache, dizziness, and rash. Children with renal insufficiency should reduce the dosage accordingly.

　　③ Omeprazole: It is a new type of gastric acid secretion inhibitor that replaces benzimidazole. Its characteristic is that it can inhibit H/K-ATPase and block the final common pathway of H secretion in gastric parietal cells. In vivo, the anti-secretory effect of omeprazole and cimetidine on histamine-induced gastric acid secretion was measured, and the former was 10 times stronger than the latter.

　　④ Famotidine: According to literature reports, famotidine is effective in treating stage I and II gastroesophageal reflux disease. Sekigochi reported that 82% of patients healed within 12 weeks of adult medication. Its application in pediatric cases is still under observation and is not yet widely used.

　　(3) Mucosal Coating Drugs: When there is ulceration or mucosal erosion in gastroesophageal reflux disease, this drug can cover the surface of the lesion to form a protective film, alleviate symptoms, and promote healing. Such drugs include sucralfate, alginate antacid Gaviscon, potassium bismuth citrate (colloidal bismuth subcitrate, CBS), and recently, in the Chinese market, double octahedral montmorillonite (Smecta) is also used to treat esophagitis, with very satisfactory efficacy. Double octahedral montmorillonite has strong covering ability for the mucosa of the digestive tract and repairs and improves the defensive function of the mucosal barrier against attacking factors through interaction with mucus glycoproteins.

　　II. Prognosis

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