Children with achalasia of the cardia

　　1. Etiology

　　The etiology of this disease is still unclear. Some believe that viral infection, toxins, nutritional deficiencies, and local inflammation may be the causes of the disease, but no viral particles were found in the electron microscopic examination of the vagus nerve and intramural plexus, which does not support the theory of viral infection. Some children have a family history, suggesting that the disease is related to genes. Clinical studies have found that mental concerns can worsen the symptoms of children, considering whether the symptoms are caused by central and autonomic nervous dysfunction due to mental stimulation, leading to the onset of the disease. Recent research has found that HLADQw antigen is closely related to the disease and an autoantibody against gastrointestinal nerves has been found in the serum of patients, suggesting that the disease has an autoimmune factor.

　　2. Pathogenesis

　　The exact pathogenesis of achalasia is still unclear, with the basic defect being abnormal neuromuscular function. Pathological findings show that there are varying degrees of muscular nerve plexus lesions in the body of the esophagus and the lower esophageal sphincter. Mononuclear cells in the Auerbach plexus infiltrate the entire ganglion cells, being replaced by fibrous tissue. The vagus nerve has Wallerian degeneration, with the loss of neuronal bodies in the dorsal motor nucleus. The esophageal smooth muscle appears normal under light microscopy, but shows detachment of the surface membrane of the microfilament bundle and cell atrophy under electron microscopy, but it is unclear whether these changes are primary or secondary. In summary, the results of histological, ultrastructural, and pharmacological studies indicate that the esophagus in achalasia has lost its innervation. The lesions are located in the brainstem, vagus nerve fibers, Auerbach plexus, and intramuscular nerve fibers, but the primary site of the disease is not clear, possibly due to diffuse neurodegenerative changes or the effect of neurotoxic substances on all the nervous system from the brain to the muscle fibers.

　　The pathophysiological mechanism of achalasia is as follows:

　　1. Neurogenic lesion

　　The patient's esophageal myenteric plexus (Auerbach plexus) has a reduction, absence, degenerative changes, and nerve fiberization of ganglion cells. The absence of pathological changes suggests an external neuropathy. The muscle bundles in the body of the esophagus and the LES area do not respond to stimulation at the ganglion level, while acetylcholine directly induces a contraction response. There are also reports that patients' esophagus has a strong response to cholinergic agents, showing intense segmental contractions. According to Cannon's law, the tissue that loses autonomic nerves is more sensitive to the neurotransmitter of the nerve conduction, indicating that the lesion is mainly in the nerve.

　　2. Involvement of inhibitory neurons

　　The neural activity in the LES region includes excitatory (cholinergic) and inhibitory (non-cholinergic, non-adrenergic NANC) types. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are inhibitory neurotransmitters of NANC, mediating smooth muscle relaxation. Patients with achalasia show a significant reduction in VIP and NO nerve fibers in the lower esophageal segment. The abnormal contraction of the LES by cholecystokinin (CCK) also suggests damage to inhibitory nerves. In addition, the response of the LES to drugs such as opiate peptides is different from that of healthy individuals, indicating abnormal receptors in neurons or muscle cells.

　　3. Abnormal Vagus Nerve Function

　　Patients with this disease have obvious disorders of gastric acid secretion, similar to symptoms after vagotomy, suggesting the presence of vagus nerve dysfunction.

　　In summary, due to factors such as the pathological changes of the vagus center and the esophageal wall nerve plexus, the lack of inhibitory neurotransmitters, denervation atrophy of the esophagus, and dysfunction of the vagus nerve, the resting pressure of the lower esophageal sphincter (LES) increases; during swallowing, the LES does not relax incompletely or cannot relax completely; the body of the esophagus lacks peristalsis and coordination, without propelling food. This causes food to remain in the esophagus. When the pressure inside the esophagus exceeds the pressure of the LES, due to gravity, only a small amount of food can slowly pass through. Long-term retention of esophageal contents can lead to esophageal dilation, elongation, and curvature, esophagitis, ulcers, or cancer. Recent research has found that some children experience peristaltic contractions in the esophagus after treatment to relieve LES obstruction. Therefore, it is believed that the non-peristaltic contraction of the esophageal body is not primary but related to LES obstruction.

　　1. Respiratory complications

　　It occurs in about 10% of patients, more明显 in children, mainly due to aspiration pneumonia, bronchiectasis, lung abscess, and pulmonary fibrosis caused by vomiting and reflux. The retention of oil in the esophagus due to aspiration of atypical mycobacteria can induce chronic pulmonary changes similar to clinical and X-ray findings of tuberculosis. The presence of acid-fast bacilli in sputum may be atypical mycobacteria and should not be mistaken for tuberculosis bacilli.

　　2. Cancer

　　According to reports, 2% to 7% of patients may be complicated with esophageal cancer, especially those with a course of disease of more than 10 years, significant esophageal dilation, and severe retention. The main cause is chronic inflammatory stimulus factors caused by food retention leading to esophagitis. Esophageal muscle layer incision or dilation after surgery cannot prevent the occurrence of cancer, and there are reports that cancer can occur many years after successful surgery. Therefore, careful observation should be made for the occurrence of esophageal cancer, and tissue biopsy should be performed in suspected cases. Huang Guojun and Zhang Wei, respectively, reported that the incidence of gender in patients with achalasia complicated with esophageal cancer is similar to that of esophageal cancer, mainly male, but the onset age of cancer with achalasia is younger than that of esophageal cancer patients. The average age of patients with achalasia is 48 to 51 years, and the age of those without achalasia is 62 to 67 years. Tumors are most commonly found in the middle segment of the esophagus, followed by the lower and upper segments.

　　3. Esophagitis

　　Due to esophageal retention of food caused by achalasia, endoscopic examination can reveal esophagitis and mucosal ulcers caused by it, ulcers can cause bleeding, and a few cases can develop spontaneous perforation and esophageal tracheal fistula. Body weakness or those who have received antibiotic treatment or have a decrease in granulocytes may be complicated with candidal infection. White spots can be seen on inflammatory mucosa in the endoscope. Smear and biopsy can confirm the diagnosis. Treatment should first perform dilation to relieve esophageal retention, for those who cannot tolerate strong dilation, suction drainage can be used to maintain esophageal emptying, and antibiotics should be used at the same time.

　　4. Other complications

　　Due to the esophageal dilation caused by achalasia, the intraluminal tension increases, leading to the complication of diaphragmatic hernia-type diverticula, which can be treated at the same time as the treatment for achalasia. A few patients may have joint complications similar to rheumatoid arthritis, and the symptoms can be relieved after the treatment of achalasia.

　　1. Difficulty in swallowing

　　Painless difficulty in swallowing is the most common and earliest symptom of the disease, accounting for 80% to 95% or more. The onset symptoms are usually relatively slow, but they can also be acute, and initially they may be mild, with only a feeling of fullness after meals. Difficulty in swallowing is often intermittent, often triggered by emotional fluctuations, anger, worry, fear, or eating cold and spicy刺激性 food. In the early stage, the difficulty in swallowing may be intermittent, light or severe, and later it may become persistent. A few patients find it more difficult to swallow liquids than solid foods, and some use this sign to distinguish their difficulty in swallowing from that caused by other esophageal organic stenosis. However, most patients find it more difficult to swallow solid foods than liquids, or have the same difficulty in swallowing both solid and liquid foods.

　　2. Food reflux and vomiting

　　The incidence of food reflux and vomiting in patients with achalasia can reach 90%. With the worsening of difficulty in swallowing and the further expansion of the esophagus, a considerable amount of content can remain in the esophagus for several hours or even several days, and it can reflux out when the body position changes. Vomiting usually occurs within 20 to 30 minutes after eating and can vomit out the previous meal or food from the night before. The contents refluxed from the esophagus, as they have not entered the stomach cavity, do not have the characteristics of stomach vomiting matter, but can be mixed with a large amount of mucus and saliva. When esophagitis or esophageal ulceration occurs, the refluxed matter can contain blood.

　　Patients may suffer from recurrent pneumonia, tracheitis, or even bronchiectasis or lung abscess due to food reflux and aspiration.

　　3. Pain

　　About 40% to 90% of patients with achalasia have pain symptoms, which vary in nature, ranging from dull pain, burning pain, pricking pain, cutting pain, or needle pain. The pain is usually located behind the sternum and in the upper middle abdomen; it can also occur in the chest and back, the right chest, the right sternal margin, and the left hypochondrium. Sometimes the pain发作 resembles angina pectoris, and even after sublingual nitroglycerin tablets, it can be relieved. The mechanism of pain occurrence may be due to the strong contraction of esophageal smooth muscle, or due to esophagitis caused by food retention. As the difficulty in swallowing gradually worsens, the further expansion of the esophagus above the obstruction can make the pain gradually subside.

　　4. Weight loss

　　Weight loss and difficulty in swallowing are related to the intake of food. For difficulty in swallowing, patients often adopt selective eating, slow eating, drinking more soup and water after meals or during meals to flush down the food, or straightening the chest and back, forceful deep breathing, or holding one's breath to assist the swallowing action, so that food enters the stomach and ensures nutrient intake. However, in patients with a long course of disease, weight loss, malnutrition, and vitamin deficiency may still occur, and cachexia is rare.

　　5. Other

　　Patients with achalasia may often have anemia, and occasionally bleeding may be caused by esophagitis. In later cases, the extremely dilated esophagus can compress the organs in the thoracic cavity, causing dry cough, shortness of breath, cyanosis, and hoarseness, etc.

　　The etiology of this disease has not been clarified, so there is currently no reliable preventive measure. Eat less and more meals, chew food finely, avoid cold and hot and irritant foods. Psychological treatment and surface agents can be given to those who are tense. Some patients adopt the Valsalva maneuver to promote the entry of food from the esophagus into the stomach, relieve the discomfort behind the sternum. Sublingual nitroglycerin can relieve esophageal spasm pain and accelerate esophageal emptying. Cardia spasm, also known as achalasia (esophageal achalasia), meg Esohage, is a decrease in the number of ganglion cells in the interspersed nerve plexus of the esophageal wall, even disappearance, which can affect the entire thoracic segment of the esophagus, but it is most obvious in the middle and lower parts of the esophagus.

　　1. Blood Routine

　　Anemia can be found in peripheral blood, and when aspiration pneumonia occurs, there may be signs of infection, such as an increased white blood cell count and an increased neutrophil count.

　　2. X-ray Examination

　　In the early stage of the disease, the chest X-ray may show no abnormalities. With the expansion of the esophagus, it can be seen that the right upper edge of the mediastinum bulges in the anteroposterior chest X-ray. When the esophagus is highly expanded, extended, and curved, the mediastinum can be widened beyond the right border of the heart, and sometimes it may be misdiagnosed as mediastinal tumor. When a large amount of food and gas is retained in the esophagus, the bubbles in the stomach disappear, and liquid levels can be seen in the esophagus. Most cases show the disappearance of the gastric bubble.

　　3. Barium Meal Examination

　　Esophageal barium meal examination is an important diagnostic examination in achalasia cases. During the examination, attention should be paid to the morphological and functional characteristics of the esophageal body and distal sphincter. The main X-ray feature of achalasia is the disappearance of esophageal peristalsis, the lack of relaxation response of the distal sphincter during swallowing, and the retention of barium at the junction of the stomach and esophagus. The wall of this part is smooth, and the lumen narrows suddenly in a beak-like shape.

　　4. Endoscopic Examination

　　Endoscopy is not very helpful in the diagnosis of this disease, but it can be used for differential diagnosis between this disease and esophageal cardia cancer and other diseases.

　　The more severe the esophageal dilation, the more obvious the mucosal inflammation. The mucosa of the lower esophagus becomes明显变白、增厚、粗糙, and may have signs of 'cracks'. In severe cases, nodular changes may occur, with erosion and superficial ulcers. When nodules, erosion, and ulcers occur, be vigilant for the occurrence of esophageal cancer.

　　5. Esophageal Manometry

　　It can reflect the esophageal motor pathology from the pathological and physiological perspective, and can confirm or diagnose the disease, and can also be used as a quantitative index for evaluating the efficacy of drug treatment, dilation, and esophageal muscle incision after esophageal function evaluation.

　　6. Esophageal Emptying Examination

　　Including radionuclide esophageal transit time, esophageal barium emptying index measurement, and water drinking test, all of which are helpful in judging the esophageal emptying function and are also used to evaluate the efficacy of treatment on esophageal function.

　　7. Acetylcholine Test

　　After normal people receive an intradermal injection of acetylcholine 5 to 10mg, there is no significant increase in esophageal peristalsis pressure. However, in patients with this disease, strong esophageal contractions can be produced within 1 to 2 minutes after injection; the esophageal pressure suddenly increases, thus causing severe pain and vomiting.

　　Diet therapy for pediatric achalasia:
　　① 6 grams of rose, 3 grams of star anise, 30 grams of silver ear, a little sugar. Steam the silver ear for 1 hour, add the rose, star anise, and sugar, simmer slightly, and take in several doses. It is used for patients with intermittent difficulty in swallowing and food reflux.
　　② 200 milliliters of milk, boiled and eaten on an empty stomach, once in the morning and once in the evening. It is used for patients with intermittent difficulty in swallowing.
　　③ 200 grams of raw radish, pounded into juice, scalded with boiling water and served warm in several doses. It is used for patients with qi stagnation and phlegm retention.
　　④ Acetic egg therapy: 15 grams of pinellia, 30 grams of white peony, 15 grams of vinegar, boiled and strained, mixed with one fresh egg, stirred well, and drunk.
　　Principles of diet for pediatric achalasia:
　　Eat less and more frequently, chew food thoroughly, and avoid eating fast, cold, and刺激性食物.

　　One. Treatment

　　The main goal of the treatment for this disease is to reduce LES pressure, improve LES relaxation function, and allow food to enter the stomach relying on gravity and esophageal pressure, thereby alleviating symptoms. The treatment includes:

　　1. General treatment

　　One should maintain an optimistic and stable mood, avoid stimuli, and if there are mental or psychological disorders, psychological treatment and necessary sedatives should be provided. Avoid cold drinks, and try to eat soft foods that are easy to empty the esophagus without irritation. Attention should be paid to the body position during sleep, maintaining a head-high, feet-low position to reduce food reflux and aspiration of refluxed material, especially in infants and young children. For children with severe vomiting and feeding difficulties, sufficient calories and fluids should be provided to prevent and treat malnutrition.

　　2. Medication treatment

　　(1) Nitrates: The administration of nitrate drugs can reduce LES pressure, which may be related to the release of NO. The main drugs include nitroglycerin and isosorbide dinitrate, which may partially relieve symptoms.

　　(2) Calcium channel blockers: These drugs block the influx of calcium ions to relax the LES. Common drugs include nifedipine, diltiazem, and verapamil. When used in combination with the first category of drugs, they are more effective than a single drug.

　　(3) Antianxiety drugs: They have a calming, antianxiety central and muscle relaxant effect.

　　(4) Smooth muscle relaxants: They relieve smooth muscle spasm and promote esophageal emptying. Drugs such as atropine scopolamine butylbromide can be used.

　　3. Esophageal dilation

　　The treatment can be performed using conventional dilators or balloons, with the latter being more effective. The dilation procedure is carried out 12 hours after fasting, requiring X-ray fluoroscopy guidance to place the balloon at the LES, with the dilation pressure varying from person to person. The dilation time is 15-60 seconds, and it can be repeated 1-2 times. There is also a method using endoscopic guidance for the balloon, which may not require X-ray monitoring. The incidence of esophageal perforation during the surgery is 1% to 5%. Routine esophageal X-ray examination should be performed after the operation, using water-soluble contrast agent to determine if there is a perforation. Balloon dilation is an effective treatment, with reports indicating that the efficacy of balloon dilation is similar to that of surgical operation, with a low incidence of complications, and it is recommended to consider it as a first-line treatment measure. The best method to judge the efficacy of the surgery is to measure the LES pressure, as a significant decrease in pressure after the operation indicates in adults

　　4. Surgical Treatment

　　Multiple internal treatments have been ineffective; esophageal tortuosity and dilation; the dilator cannot pass through; it cannot be ruled out that there is esophageal cancer; those who cannot tolerate dilation; surgical treatment can be performed. The surgical methods include narrowing the expanded esophageal lumen; shortening the elongated esophageal curvature; dilating the LES area, partial resection or bypass surgery of the esophagus and stomach; fundoplication and esophageal muscle incision, etc. Currently, the modified Heller procedure is mostly used, which involves a longitudinal incision of the sphincter in the narrowed segment while keeping the mucosa intact, and simultaneously performing a fundoplication. The success rate of surgery is 80% to 90%, and it can prevent gastroesophageal reflux. Morris et al. reported that 10 children who underwent transabdominal surgery were followed up for 10 years, with 8 cured and 2 improved. It is proposed that the management of achalasia in childhood should include transabdominal myotomy and combined anti-reflux fundoplication (Nissen) surgery.

　　5. Local Injection of the Sphincter

　　In recent years, the injection of botulinum toxin in the LES area under endoscopic visualization has been applied in clinical practice. Botulinum toxin is a neuromuscular cholinergic blocking agent that can reduce the cholinergic innervation of the sphincter's excitability and relieve symptoms. The injection dose is 20U per direction, totaling 80U for four directions. The incidence of surgery combined with perforation is zero. It has been reported that the initial effective rate is 90%, and the long-term (more than 6 months) effective rate is 71%, with an average effective time of 1.3 years after initial treatment. Randomized double-blind controlled studies have found that the injection of botulinum toxin into the lower esophageal sphincter has a similar degree of symptom relief as balloon dilation. Some suggest that this procedure can be used for those who cannot receive dilation therapy and surgery.

　　II. Prognosis

　　During follow-up, although the esophageal stricture was relieved, eating improved, and the esophageal emptying was good without retention, the expanded esophagus could not return to its original diameter, the peristaltic waves still maintained a slow progression and contraction, and remained twisted and enlarged.