Gastroesophageal reflux disease is a disease in which the contents of the stomach and duodenum flow back into the esophagus causing clinical symptoms and/or inflammation of the esophagus. GERD patients may have only clinical symptoms without esophageal inflammation, while those with esophagitis symptoms may not necessarily have a parallel relationship between clinical symptoms and the degree of inflammation. The main clinical manifestations are heartburn, retrosternal pressure, acid reflux and regurgitation, and in severe cases, dysphagia, upper gastrointestinal bleeding, Barrett’s esophagus and esophageal adenocarcinoma.
1.Etiology and pathogenesis
GERD is a kind of upper gastrointestinal tract motility disorder, caused by a variety of factors, GERD is a common disease in the elderly, the onset of factors related to the decline of systemic physiological function, chronic diseases. The pathogenesis of GERD is related to gastric acid, that is, the reflux of gastric acid from the stomach to the esophagus, which exposes the esophagus to gastric acid for too long and causes clinical symptoms and/or damage to the esophageal mucosa. Under normal conditions, the esophagus has functions to defend against gastric acid and duodenal contents, including anti-reflux barrier, esophageal contouring function and resistance of esophageal mucosal tissue.
1.1 Anti-reflux barrier of esophagus The anti-reflux barrier of esophagus refers to a complex area at the junction of esophagus and stomach, including the lower esophageal sphincter (LES), the location of the ventral segment of LES, the foot of diaphragm, the diaphragmatic esophageal ligament, and the acute angle between esophagus and gastric fundus (His angle). Structural and functional defects in each of these parts can cause gastroesophageal reflux, the most important of which is the functional state of the LES. In normal people, the LESP is 10-30 mmHg at rest, which is a high pressure band to prevent reflux of gastric contents into the esophagus. If the structure of the LES is damaged after cardia inactivation surgery, the LESP may decrease, making it easy to complicate reflux esophagitis. Some other factors, such as certain hormones (cholecystokinin, glucagon, pancreatic glucagon), food (high-fat food, chocolate, coffee, etc.), and drugs (calcium antagonists, valium, theophylline) can lower LESP. Increased intra-abdominal pressure (pregnancy, constipation, vomiting, ascites, etc.) and increased gastric pressure (gastric dilatation, delayed gastric emptying, etc.) can cause a corresponding decrease in LESP and lead to gastroesophageal reflux. It has been found that transient LES relaxation (TLESR) is more frequent in some GERD patients. Studies have shown that the development of GERD is mainly related to LES dysfunction, including low LESP and excessive and frequent TLESR, and some studies have shown that the length of LES plays an important role in anti-reflux, which does not vary with age in the normal population.
1.2 Esophageal acid clearance Esophageal acid clearance is divided into two steps: the majority is cleared by esophageal peristalsis. The remaining part is neutralized by saliva. Therefore, both volume clearance and salivary dysfunction may prolong esophageal acid clearance, exposing the esophageal mucosa to acid for a longer period of time and leading to esophageal inflammation.
1.3 Esophageal mucosal defense The esophageal mucosal defense includes pre-epithelial defense, epithelial defense, and post-epithelial defense. The pre-epithelial defense includes surface mucus, immobile water layer, and surface bicarbonate ions. It does not provide much defense against refluxed gastric and duodenal fluids. The lamina propria of the epithelium is a complex squamous epithelium with secretory capacity, which has both structural and functional defense against acid damage. The post-epithelial defense mainly refers to the blood supply of the mucosa, which provides nutrients and oxygen to the cells and eliminates toxic metabolites. Therefore, when the mucosal defense of the esophagus decreases, it will easily lead to esophageal inflammation.
1.4 Delayed gastric emptying High-fat diet, smoking, pyloroduodenal dyskinesia, as well as many systemic diseases and medications can slow gastric emptying and promote gastroesophageal reflux. Delayed gastric liquid and solid emptying has been found in patients with CERD, and the solid emptying time is positively correlated with the total pH score. Delayed gastric emptying may be an important factor in the pathogenesis of CERD. In conclusion, the occurrence of GERD is related to all of the above factors. The occurrence of GERD is related to the nature of the reflux, the time of contact between the reflux and esophageal mucosa and the resistance of the esophageal mucosa.
2.Diagnosis
In addition to typical or atypical GERD symptoms, the diagnosis of GERD also includes objective evidence of pathology caused by GERD, such as endoscopy, barium esophageal meal, X-ray, nuclear and esophageal motor function tests (esophageal manometry, 24h esophageal pH test). Pathological changes may include: ① thickening of the basal cell layer of the squamous epithelium, up to 16%~18% of the entire thickness of the squamous epithelium. The papillae are prolonged in the epithelial lumen, exceeding 2/3 of the epithelial thickness. ③ Inflammatory cell infiltration in the lamina propria. ④ ballooning of squamous epithelium, with lightly stained cytoplasm and vacuolated, irregular or concentrated nuclei. ⑤ Erosion and ulceration. Endoscopy is an essential tool to determine the severity of esophagitis and can be performed by mucosal biopsy to understand the histological changes. It can also assist in the diagnosis of esophageal hiatal hernia and the presence or absence of Barrett’s esophagus. Endoscopic esophagitis may show the following signs: mucosal congestion, oozing and granular changes in the lower esophagus, blurred, uneven and upwardly shifted dentate lines, somewhat flaky or striped erosions, or fused erosions, esophageal ulcers, strictures, short esophagus, etc. Esophageal manometry can measure LESP, LES length and location, LES relaxation pressure, esophageal body pressure and upper esophageal sphincter pressure. It is generally believed that the resting pressure of the LES is 10-30 mmHg, and if the LESP is <6 mmHg, it is likely to lead to reflux. LESP measurement can be used for pressure assessment before anti-reflux surgery, to guide the surgical approach and to monitor the post-surgical outcome. Because LESP and esophageal body pressure overlap with those of normal subjects, it is considered by many to be an auxiliary diagnostic criterion only. Long-term intraesophageal pH monitoring is more accurate than 24-h monitoring and has been recognized as the gold standard for the diagnosis of GERD. It can provide information on the presence of pathological reflux, the degree and duration of reflux, the relationship between reflux and body position and the occurrence of symptoms, and the ability to clear acid from the esophagus. 24-h intraesophageal pH monitoring is highly sensitive but poorly specific, while endoscopy is highly specific but poorly sensitive, and the two are complementary. Color Doppler has been found to be more sensitive and easier to use than pH monitoring. Although there are no clear criteria for evaluating the severity of reflux esophagitis with color Doppler images, this method can be used to screen children with reflux esophagitis. In addition, experimental treatment with high doses of omeprazole can be used to clarify the diagnosis. The omeprazole test is sensitive and specific for the diagnosis of GERD. This method not only saves money, but also avoids the use of invasive diagnostic methods.
3.Treatment
The treatment of GERD aims to control symptoms, cure esophagitis, reduce recurrence and prevent complications. The treatment measures include life guidance, medical treatment and surgical treatment.
3・1 Life guidance In order to reduce recumbency and nocturnal reflux. The foot of the bed at the head end can be elevated by 15-20 cm, and attention should be paid to reducing all factors that affect the increase of abdominal pressure, such as obesity and constipation. Avoid foods that lower LESP, such as high-fat foods, chocolate, etc. Avoid the application of drugs that lower LESP and drugs that affect delayed gastric emptying, such as anticholinergics and tricyclic antidepressants.
3・2 Internal treatment When using drugs to treat GERD, attention must be paid to the criteria for evaluating the efficacy, i.e. the classification of esophagitis and the severity of symptoms, which sometimes do not exactly show a good parallel relationship. Therefore, symptom control after drug treatment does not necessarily mean that esophagitis has been cured, and vice versa.
3・2・1 Anti-acid therapy Anti-acid therapy is one of the important tools for GERD, but acid suppression cannot improve the dynamics of the esophagus and stomach and cannot fundamentally stop reflux, while strong acid suppression can delay gastric emptying. It has been found that eliminating acid reflux can stabilize the cell proliferation activity in the lumen of Barrett’s esophagus. Whether this finding can be used to prevent cancer in Barrett’s esophagus needs further study. (1) Acid control agents: mainly neutralize gastric acid, commonly used drugs include alkaline salts containing aluminum, magnesium, bismuth, etc. and their different formulations of compound preparations, which are weak and can be used to relieve symptoms in mild cases. H2 receptor antagonists: it can better control the symptoms of moderate GERD and (or) reduce and cure esophagitis. ③Proton pump inhibitors: are powerful acid suppressants, currently used in the application of omeprazole, pantoprazole, etc.. These drugs mainly treat severe GERD or H2 receptor antagonist treatment is ineffective, can be more obvious to control the symptoms and cure esophagitis. Studies have shown that omeprazole is safe and effective in treating GERD symptoms in children, and is also effective in children who have failed anti-reflux surgery or other medical treatments. Pantoprazole IV-oral regimens for GERD patients have been found to eliminate symptoms quickly and have a high cure rate. For patients who cannot be treated with oral medication, this regimen can safely and reliably suppress gastric acid, and the oral and intravenous doses are the same, and no dose adjustment is required when the mode of administration is changed.
3・2・2 Gastric mucosal protective agent Aluminum sulfate can form a complex with proteins on the inflamed surface of the esophagus and cover the damaged mucosal surface, so that its contact time with gastric acid is reduced, and it has a certain protective effect on the esophageal mucosa. Because of the weak effect of gastric mucosa protector, it is mostly used in combination with other types of drugs.
3・2・3 Prokinetic drugs GERD is an esophageal motility disorder, prokinetic drugs in theory have the effect of increasing LESP, promote gastric emptying and improve esophageal peristaltic function. Cisapride is a total gastrointestinal prokinetic agent, which stimulates the 5HT4 receptors of the motor neurons of the intermuscular plexus, causing the release of acetylcholine, enhancing the peristaltic contraction of the esophageal body, increasing the pressure of the esophageal sphincter, and increasing gastric emptying, thus reducing gastroesophageal reflux and relieving reflux symptoms]. Intravenous erythromycin has been found to enhance gastric emptying and esophageal motility like the effect of gastric motility, but it has not been used in clinical practice. It has been found that H. pylori increases the recurrence rate of reflux esophagitis, therefore, timely drug eradication of H. pylori in GERD patients can prolong the recurrence interval. Although drug treatment can control the symptoms of GERD and temporarily cure or reduce esophagitis, the movement disorder is not removed and the symptoms and esophagitis can recur once the treatment is interrupted.
3・3 Surgical treatment Reflux esophagitis often persists and relapses after drug withdrawal, pushing the disease to surgical treatment. A cautious approach to anti-reflux surgery is necessary, and both physicians and patients need to weigh the pros and cons.
3・3・1 Indications The following cases can be considered for surgical treatment: ① those who have been treated medically but still have severe symptoms and esophagitis; ② those with persistent BARRET ulcers and bleeding, especially those with combined atypical hyperplasia; ③ those with recurrent peptic esophageal strictures treated by dilatation; ④ those with significant esophageal hiatal hernia; ⑤ young people who need long-term heavy medication; ⑥ those who have failed anti-reflux surgery in the past. Before LF surgery, in addition to routine examination, the main tests include upper gastrointestinal barium meal examination, esophagoscopy, 24h esophageal pH measurement to understand the function of the lower esophageal sphincter. The presence of pathological factors such as esophageal hiatal hernia, history of splenectomy, short esophagus, etc., which may hinder the completion of laparoscopic surgery, should also be known.
3.3.2 Surgical approach Many procedures have been explored over the years to treat GERD. 1951 Allison used the method of esophageal hiatal reconstruction to treat GERD, which was soon found to have a high failure and recurrence rate. In 1955, Belsey and Nissen each described a fundoplication for GERD, and in 1991, Daallemagne and Nethanson reported laparoscopic fundoplication (LF) and hepatic round ligament pancreatic fixation suture for GERD, respectively, with good recent results. Good recent results were achieved. The success rate of open fundoplication (OF) for GERD with typical symptoms is 90%, and the success rate of LF is more than 90%. LF has better respiratory function, less anesthesia, shorter hospital stay, and the same postoperative symptom relief compared to OF. Therefore, it is becoming the new standard of surgical treatment for GERD.
Currently, the Nissen fundoplication is the gold standard for the treatment of GERD. For patients with poor esophageal motility, it is recommended to use Toupet (partial) fundoplication to fold the fundus 270 degrees, although its anti-reflux effect is not as complete as Nissen, but it can prevent postoperative dysphagia. For patients with short esophagus, Collis gastroplasty is added, where a tubular stomach is created as the distal esophagus and a general fundoplication is performed on the newly created esophagus.
LF is safe and effective in reducing the typical symptoms of GERD. However, LF is not as effective for atypical symptoms of GERD as it is for typical symptoms, with an efficiency of only 50%-75%. The effectiveness of LF is only 50%~75%. The effect of acid-suppressing drugs is better to reduce atypical symptoms. Treatment of atypical symptoms with LF must be chosen carefully and with prognosis in mind. Some patients who have previously undergone other anti-reflux surgery have relapsed or have severe postoperative dysphagia and may be reoperated with LF. Although technically challenging, laparoscopic surgery is safe and highly effective. Therefore, patients who have undergone unsuccessful anti-reflux surgery should be reoperated under the supervision of an experienced surgeon. Postoperative results were observed by endoscopy and functional examinations. A barium meal of the upper gastrointestinal tract was performed on the second postoperative day to determine the position and function of the anti-reflux valve. At 1 month postoperatively, a follow-up examination was performed to check the surgical results and to observe any surgical complications. At 4 months postoperatively, gastroscopy and esophageal manometry were repeated to observe the surgical results. Some studies have shown that CT can provide an accurate estimate of the structure of the gastroesophageal junction after Nissen fundoplication. In post-Nissen fundoplication patients, the use of CT is complementary to endoscopy and functional examination. Operated by an experienced surgeon, the LF procedure has a low failure rate. Extensive esophageal relaxation, safe diaphragm closure, esophageal length measurement, and avoidance of conditions leading to increased abdominal pressure can further reduce the failure rate.
The main intraoperative complication of LF is pneumothorax. Because the left wall pleura is exposed and may be torn, it can cause CO2 gas from the abdomen to enter the pleural cavity. Some studies have reported that pneumothorax occurs in about 15-2% of patients undergoing LF, and it can be diagnosed early by timely monitoring of PaCO2, total lung volume, and airway pressure. Pneumothorax is better treated with positive end-expiratory pressure (PEEP), which reduces the pressure gradient between the abdomen and the pleural cavity, and when the gradient is reduced or reversed, the gas leaves the chest cavity. This non-invasive method is very effective in treating pneumothorax and does not require thoracentesis.
The main postoperative complication is dysphagia. Short-term postoperative dysphagia is usually due to distension of the surgical site and resolves within a few weeks. Patients may be advised to take a soft or liquid diet until 1 month postoperatively. For patients with persistent dysphagia after surgery, a barium swallow test is performed and endoscopic esophageal dilatation is feasible. Patients who have parcel injury, sliding fundoplication, or peri-esophageal hernia formation will need to undergo surgery again. In addition, laparoscopic procedures for GERD include hepatic round ligament cardia fixation suture and lower esophagoplasty. These two procedures have a short follow-up period and have not been finally evaluated.