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胃食道逆流疾病 (Gastroesophageal Reflux disease, GERD) 
      胃食道逆流本身是一種生理現象，每個人都可能經歷過不等程度的逆流，但是一旦持續、嚴重的發生，就是一種病態，稱為胃食道逆流疾病(gastroesophageal reflux disease,GERD)。這是一種由於胃或小腸內容物，如胃酸、膽汁、消化酵素等逆流到食道，所引起之食道或咽喉及呼吸道等不適症狀之疾病，其中約有20﹪病人，因長期或強烈逆流物刺激，造成食道發炎病變，包括糜爛、潰瘍、食道管腔纖維狹窄等，則可稱為逆流性食道炎(reflux esophagitis)。
      GERD的病人其黏膜層的傷害程度，主要與胃酸的濃度及接觸時間的長短有關。大多數病人胃酸分泌速度正常，大部份是與下食道括約肌鬆弛有關，次要的原因才是胃排空減緩、胃酸過度分泌、食道蠕動功能不佳等，若同時存在裂孔疝氣(hiatal hernia)，則會增加括約肌鬆弛的發生，而使症狀加重。
原因
             我們身體正常狀況下有抵抗胃食道逆流的機制，包括胃食道交界的解剖構造及食道對胃酸的廓清(acid clearance)。  胃食道交界的構造對於防止胃食道逆流最重要的就是下食道括約肌(lower esophageal sphincter, LES)。一旦下食道括約肌和胃之間的壓力差消失，逆流的現象就可能發生，例如括約肌的肌肉衰弱，或是支配神經引起異常的舒張。其他次發性下食道括約肌功能異常的原因包括似硬皮症疾病(scleroderma-like disease)、肌肉病變、懷孕、抽煙、藥物(如一些β-adrenergic agents、aminophylline、nitrates、鈣離子阻斷劑、progesterone、benzodiazepines、anticholinergics、antidepressants、lidocaine、prostaglandins)、食道炎，及曾該處動過外科手術或氣球擴張術。食道裂孔疝氣(hiatal hernia)也是下食道括約肌功能受隕常見的原因之一，尤其是在年紀較大的病人。
        影響食道對胃酸廓清能力的因素有重力、食道的收縮蠕動、唾液和食道分泌碳酸鹽的能力。食道當中出現逆流物的時候，會出現一種所謂的次發性蠕動(Secondary peristalsis)將之推回胃部。而仍殘留的少量酸性物質就會靠唾液和食道分泌物中的碳酸鹽進行中和。一旦上述食道廓清酸性物質的能力受損，食道黏膜便受到酸的持續刺激，組織結構受到傷害，臨床症狀也於是產生。

症狀
       GERD的臨床症狀，與其傷害的位置有關，典型症狀包括：胸口灼熱(heart burn)、胃酸逆流(acid regurgitation)、吞嚥困難等；非典型症狀包括：內因性氣喘、慢性夜間咳嗽、聲音沙啞、逆流性喉炎、非心因性胸痛、夜間盜汗等，雖然多數的GERD無明顯的逆流性食道炎，而逆流性食道炎也可能無明顯的症狀，通常症狀會加重於飯後、平躺、彎腰、情緒不穩、激烈運動後。
      心口灼熱感(heart burn)是GERD最典型的症狀。此症狀是因為發炎的食道黏膜接觸到逆流而來的胃內容物。一般容易出現在進食大量食物後、運動、身體向前傾和躺下的時候。酸逆流、打嗝、噁心感、胸痛都是胃食道逆流疾病可能出現的症狀，但是事實上如果沒有食道炎的情形，大部份患者是沒有任何上述症狀的。如果出現吞嚥困難、體重減輕、腸胃道出血，和貧血時，代表出現了胃食道逆流疾病的併發症，需要儘快就醫治療。
        胃食道逆流還有一些常被誤認為是其他疾病的非典型症狀，包括氣喘、咳嗽、支氣管炎、肺纖維化、吸入性肺炎、球狀異物感、喉炎、聲音沙啞、陣發性喉痙攣、鼻竇炎和牙釉質喪失(dental enamel loss)。所以有這些症狀出現時，仍需小心評估胃食道逆流疾病的可能性
      GERD的合併症有食道狹窄、出血或穿孔等，還有一種Barrett慢性食道炎，是由於長期逆流性傷害，會增加細胞化生(metaplasia)和癌病變的機會。

檢查
(一)內視鏡檢查：
      內視鏡可以直接看到食道黏膜，必要時還可進行切片，因此是最普遍使用的診斷工具，可用來評估食道黏膜傷害的程度，包括糜爛、潰瘍、狹窄、食道癌等。內視鏡下對逆流性食道炎的分類，較常用的是洛杉磯分類系統，以黏膜破損(mucosal break)為主，分類較明確，且把延伸範圍包含在內(如表)。
GERD之洛杉磯分類系統(LA classification)
A級 : 一條(或多條)黏膜破損小5mm，並不延伸超過兩條黏膜皺摺
B級 : 一條(或多條)黏膜破損大5mm，並不延伸超過兩條黏膜皺摺
C級 : 黏膜破損在兩條黏膜皺摺間延續，但是不超過75﹪的圓周
D級 : 黏膜破損互相延續，且超過75﹪的圓周
 
(二)食道鋇劑攝影：
     若在攝影中發現逆流的現象，可加以診斷。這方法敏感度和特異性低，並不是一項好的診斷檢查，但可同時診斷裂孔疝氣、食道狹窄、或其他結構上的病變。
(三)24小時食道酸鹼值監測：
       在下食道括約肌上方約5公分處，放置電極來測量食道內酸鹼度，電腦可自動分析逆流次數、最長逆流時間、pH小於4的時間等，對於非典型症狀者，如不明原因胸痛或氣喘，或內視鏡下無明顯變化者，在診斷上更屬重要。
(四)食道動力學檢查：
       主要評估食道的蠕動功能及下食道括約肌的壓力。有逆流症狀的病人中，約有30-50﹪的人下食道括約肌壓力是正常的，而正常人也有10﹪左右下食道括約肌壓力較低。當檢測出病人下食道括約肌壓力低時，即表示病人對藥物治療的失敗率或復發率較高，可以建議病人接受手術治療。

治療
      GERD是一種慢性疾病，大多數有症狀的病患必須長期治療，治療方式包括：
(一)生活型態的調整：如抬高床頭至少15公分，限制吸菸、喝酒及刺激性食物，節制飲食，避免暴飲暴食等。
(二)藥物治療：制酸劑，第二型組織胺受體拮抗劑(H2-blocker)，蠕動促進劑，質子幫浦抑制劑等。
(三)手術治療：少數對內科療法不佳的病患。

         胃食道逆流是一種長期復發性疾病，且長時間可能造成巴氏食道症又會提高罹患食道癌的可能性，因此長時間適宜的治療是必需的。
(1) 非藥物治療：
        胃食道逆流的治療要從生活型態的調整開始。食物的選擇上，建議選用低脂高蛋白的食物以促進胃的排空。同時，要盡量避免柑桔類的果汁、咖啡、巧克力、蕃茄類製品和酒精飲料，因為它們可能惡化逆流的症狀。香煙中的尼古丁會降低下食道括約肌的壓力，所以對於此類病人要鼓勵戒菸。此外，睡前2-3小時不要進食並且將頭墊高睡，以幫助食道廓清酸性物質，減少夜間的不適。雖然有部份的人在減肥之後可以減輕逆流的症狀，但是肥胖對於胃食道逆流的產生是否有影響，目前仍有爭議。
(2) 藥物調整： 許多藥物會造成胃食道逆流的產生或加重症狀。因此，對於患有胃食道逆流的病人要避免給予anticholinergics、sedatives、鈣離子阻斷劑和theophylline。另外還有一些藥物，如硫酸鐵(iron sulfate)、NSAIDs、doxycycline和鉀錠會直接傷害食道黏膜，因此要避免使用或是以大量開水服用。

(3) 藥物治療：
(I) 制酸劑(antacids)：
        致酸劑可以快速解除症狀，但是需避免使用超過兩個星期，因為這可能會使我們忽略可能存在著更嚴重的情況。可能副作用包括鹽分過多(salt overload)、腹瀉、便秘、高鈣血症和影響部份口服抗生素的吸收，主要發生在老年人。對於洗腎病人，含鋁的製酸劑可導致腦部病變和軟骨症(osteomalacia)，需特別小心。

(II)第二型組織胺受體拮抗劑(H2 receptor antagonists)
         H2 antagonists可用來解除胃食道逆流的症狀和輕微食道炎的治療。同等效力的各種H2 antagonists 在解除症狀上效果一樣，大約都在40-50%。對於食道炎整體而言的治癒率也有50%。如果睡前服用，它在解除夜間症狀方面，比質子幫浦阻斷劑(proton pump inhibitors, PPIs)更加有效。一般來說H2 antagonists的副作用不大，比較需要注意的是cimetidine會減低肝臟P450系統對其他藥物的代謝，包括warfarin、dilantin、theophylline、procainamide和benzodiazepine等。此外，在腎功能不全的病人H2 antagonist的劑量必須調低。

 (III)質子幫浦阻斷劑 (Proton Pump Inhibitors, PPIs)
         PPIs用來治療各種腐蝕性食道炎以及解除逆流症狀。同等效力的各種PPIs治療的效果相同，治癒率皆在70-90%。和H2 antagonists相較，它促進癒合的速度較快，維持症狀控制的效果較好，同時也可使用在對於H2 antagonists沒有反應的食道炎。
        PPIs的副作用一般來說也不大，包括噁心感、腹瀉和頭痛。慢性使用的病人同時要注意有無Vit B12缺乏的情形。Omeprazole和cimetidine一樣是由肝臟的P450系統代謝，所以也必須注意藥物的交互作用，除此之外，PPIs很少會產生藥物的交互作用。
    

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Gastroesophageal Reflux Disease (GERD)
      Gastroesophageal reflux disease (GERD), gastro-oesophageal reflux disease (GORD), gastric reflux disease, acid reflux disease, or reflux (in babies and young children) is a chronic symptom of mucosal damage caused by stomach acid coming up from the stomach into the esophagus.
      GERD is usually caused by changes in the barrier between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter, which normally holds the top of the stomach closed, impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia. These changes may be permanent or temporary.
      Treatment is typically via lifestyle changes and medications such as proton pump inhibitors, H2 receptor blockers or antacids with or without alginic acid. Surgery may be an option in those who do not improve. In the Western world between 10 and 20% of the population is affected.
Signs and symptoms
Adults
      The most-common symptoms of GERD in adults are heartburn and regurgitation. Less-common symptoms include pain with swallowing/sore throat, increased salivation (also known as water brash), nausea, chest pain, and coughing.
      GERD sometimes causes injury of the esophagus. These injuries may include one or more of the following:
● Reflux esophagitis – necrosis of esophageal epithelium causing ulcers near the junction of the stomach and esophagus
● Esophageal strictures – the persistent narrowing of the esophagus caused by reflux-induced inflammation
● Barrett's esophagus – intestinal metaplasia (changes of the epithelial cells from squamous to intestinal columnar epithelium) of the distal esophagus
● Esophageal adenocarcinoma – a rare form of cancer
      Some people have proposed that symptoms such as sinusitis, recurrent ear infections, and idiopathic pulmonary fibrosis are due to GERD; however, a causative role has not been established.

Children
       GERD may be difficult to detect in infants and children, since they cannot describe what they are feeling and indicators must be observed. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up, coughing, and other respiratory problems, such as wheezing. Inconsolable crying, refusing food, crying for food and then pulling off the bottle or breast only to cry for it again, failure to gain adequate weight, bad breath, and belching or burping are also common. Children may have one symptom or many; no single symptom is universal in all children with GERD.
      Of the estimated 4 million babies born in the US each year, up to 35% of them may have difficulties with reflux in the first few months of their lives, known as 'spitting up'. One theory for this is the "fourth trimester theory" which notes most animals are born with significant mobility, but humans are relatively helpless at birth, and suggests there may have once been a fourth trimester, but children began to be born earlier, evolutionarily, to accommodate the development of larger heads and brains and allow them to pass through the birth canal and this leaves them with partially undeveloped digestive systems.
      Most children will outgrow their reflux by their first birthday. However, a small but significant number of them will not outgrow the condition. This is particularly true when a family history of GERD is present.

Barrett's esophagus
      GERD may lead to Barrett's esophagus, a type of intestinal metaplasia, which is in turn a precursor condition for esophageal cancer. The risk of progression from Barrett's to dysplasia is uncertain, but is estimated at about 20% of cases. Due to the risk of chronic heartburn progressing to Barrett's, EGD every five years is recommended for people with chronic heartburn, or who take drugs for chronic GERD.

Causes
       GERD is caused by a failure of the lower esophageal sphincter. In healthy patients, the "Angle of His"—the angle at which the esophagus enters the stomach—creates a valve that prevents duodenal bile, enzymes, and stomach acid from traveling back into the esophagus where they can cause burning and inflammation of sensitive esophageal tissue.

Factors that can contribute to GERD:
● Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors.
● Obesity: increasing body mass index is associated with more severe GERD. In a large series of 2000 patients with symptomatic reflux disease, it has been shown that 13% of changes in esophageal acid exposure is attributable to changes in body mass index.
● Zollinger-Ellison syndrome, which can be present with increased gastric acidity due to gastrin production.
● A high blood calcium level, which can increase gastrin production, leading to increased acidity.
● Scleroderma and systemic sclerosis, which can feature esophageal dysmotility.
● The use of medicines such as prednisolone.
● Visceroptosis or Glénard syndrome, in which the stomach has sunk in the abdomen upsetting the motility and acid secretion of the stomach.

      GERD has been linked to a variety of respiratory and laryngeal complaints such as laryngitis, chronic cough, pulmonary fibrosis, earache, and asthma, even when not clinically apparent. These atypical manifestations of GERD are commonly referred to as laryngopharyngeal reflux (LPR) or as extraesophageal reflux disease (EERD).
       Factors that have been linked with GERD, but not conclusively:
● Obstructive sleep apnea
● Gallstones, which can impede the flow of bile into the duodenum, which can affect the ability to neutralize gastric acid
       In 1999, a review of existing studies found that, on average, 40% of GERD patients also had H. pylori infection. The eradication of H. pylori can lead to an increase in acid secretion,[16] leading to the question of whether H. pylori-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity.

Diagnosis
       Endoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach: This is a complication of chronic gastroesophageal reflux disease and can be a cause of dysphagia or difficulty swallowing.
       The diagnosis of GERD is usually made when typical symptoms are present. Reflux can be present in people without symptoms and the diagnosis requires both symptoms or complications and reflux of stomach content.
       Other investigations may include esophagogastroduodenoscopy (EGD). Barium swallow X-rays should not be used for diagnosis. Esophageal manometry is not recommended for use in diagnosis being recommended only prior to surgery. Ambulatory esophageal pH monitoring may be useful in those who do not improve after PPIs and is not needed in those in whom Barrett's esophagus is seen. Investigations for H. pylori is not usually needed.
      The current gold standard for diagnosis of GERD is esophageal pH monitoring. It is the most objective test to diagnose the reflux disease and allows monitoring GERD patients in their response to medical or surgical treatment. One practice for diagnosis of GERD is a short-term treatment with proton-pump inhibitors, with improvement in symptoms suggesting a positive diagnosis. Short-term treatment with proton-pump inhibitors may help predict abnormal 24-hr pH monitoring results among patients with symptoms suggestive of GERD.

Endoscopy
       Endoscopy, the looking down into the stomach with a fibre-optic scope, is not routinely needed if the case is typical and responds to treatment. It is recommended when people either do not respond well to treatment or have alarm symptoms, including dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes. Some physicians advocate either once-in-a-lifetime or 5- to 10-yearly endoscopy for people with longstanding GERD, to evaluate the possible presence of dysplasia or Barrett's esophagus.
      Biopsies performed during gastroscopy may show:
● Edema and basal hyperplasia (nonspecific inflammatory changes)
● Lymphocytic inflammation (nonspecific)
● Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
● Eosinophilic inflammation (usually due to reflux): The presence of intraepithelial eosinophils may suggest a diagnosis of eosinophilic esophagitis (EE) if eosinophils are present in high enough numbers. ● Less than 20 eosinophils per high-power microscopic field in the distal esophagus, in the presence of other histologic features of GERD, is more consistent with GERD than EE.
● Goblet cell intestinal metaplasia or Barrett's esophagus
● Elongation of the papillae
● Thinning of the squamous cell layer
● Dysplasia
● Carcinoma
       Reflux changes may not be erosive in nature, leading to "nonerosive reflux disease".

Differential diagnosis
       Other causes of chest pain such as heart disease should be ruled out before making the diagnosis. Another kind of acid reflux, which causes respiratory and laryngeal signs and symptoms, is called laryngopharyngeal reflux (LPR) or "extraesophageal reflux disease" (EERD). Unlike GERD, LPR rarely produces heartburn, and is sometimes called silent reflux.

Treatment
       The treatments for GERD include lifestyle modifications, medications, and possibly surgery. Initial treatment is frequently with a proton-pump inhibitor such as omeprazole.
Lifestyle
       Certain foods and lifestyle are considered to promote gastroesophageal reflux, but most dietary interventions have little supporting evidence. Avoidance of specific foods and of eating before lying down should only be recommended to those in which they are associated with the symptoms. Foods that have been implicated include coffee, alcohol, chocolate, fatty foods, acidic foods, and spicy foods. Weight loss and elevating the head of the bed are generally useful. Moderate exercise improves symptoms, however in those with GERD vigorous exercise may worsen them. Stopping smoking and not drinking alcohol do not appear to result in significant improvement in symptoms.

Medications
       The primary medications used for GERD are proton-pump inhibitors, H2 receptor blockers and antacids with or without alginic acid.
       Proton-pump inhibitors (PPIs), such as omeprazole, are the most effective, followed by H2 receptor blockers, such as ranitidine. If a once daily PPI is only partially effective they may be used twice a day. They should be taken one half to one hour before a meal. There is no significant difference between agents in this class. When these medications are used long term, the lowest effective dose should be taken. They may also be taken only when symptoms occur in those with frequent problems. H2 receptor blockers lead to roughly a 40% improvement.
       The evidence for antacids is weaker with a benefit of about 10% (NNT=13) while a combination of an antacid and alginic acid (such as Gaviscon) may improve symptoms 60% (NNT=4). Metoclopramide (a prokinetic) is not recommended either alone or in combination with other treatments due to concerns around adverse effects. The benefit of the prokinetic mosapride is modest.
       Sucralfate has a similar effectiveness to H2 receptor blockers; however, sucralfate needs to be taken multiple times a day, thus limiting its use. Baclofen, an agonist of the GABAB receptor, while effective, has similar issues of needing frequent dosing in addition to greater adverse effects compared to other medications.

Surgery
       The standard surgical treatment for severe GERD is the Nissen fundoplication. In this procedure, the upper part of the stomach is wrapped around the lower esophageal sphincter to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia. It is only recommended in those who do not improve with PPIs. Benefits are equal to medical treatment in those with chronic symptoms. In addition, in the short and medium term, laparoscopic fundoplication improves quality of life compared to medical management. When comparing different fundoplication techniques, partial posterior fundoplication surgery is more effective than partial anterior fundoplication surgery.
       In 2012 the FDA approved a device called the LINX, which consists of a series of metal beads with magnetic cores that are placed surgically around the lower esophageal sphincter, for those with severe symptoms that do not respond to other treatments. Improvement of GERD symptoms are similar to those of the Nissen fundoplication, although there is no data regarding long-term effects. Compared to Nissen fundoplication procedures, the procedure has shown a reduction in complications such as gas bloat syndrome that commonly occur. Adverse responses include difficulty swallowing, chest pain, vomiting, and nausea. Contraindications that would advise against use of the device are patients who are or may be allergic to titanium, stainless steel, nickel, or ferrous iron materials. A warning advises that the device should not be used by patients who could be exposed to, or undergo, magnetic resonance imaging (MRI) because of serious injury to the patient and damage to the device.

Pregnancy
       In pregnancy, dietary modifications and lifestyle changes may be attempted, but often have little effect. Calcium-based antacids are recommended if these changes are not effective. Aluminum- and magnesium-based antacids are also safe, as is ranitidine and PPIs.

Infants

Infants may see relief with changes in feeding techniques, such as smaller, more frequent feedings, changes in position during feedings, or more frequent burping during feedings. They may also be treated with medicines such as ranitidine or proton pump inhibitors. Proton pump inhibitors however have not been found to be effective in this population and there is a lack of evidence for safety.

Overtreatment

The use of acid suppression therapy is a common response to GERD symptoms and many patients get more of this kind of treatment than their individual case merits. The overuse of this treatment is a problem because of the side effects and costs which the patient will have from undergoing unnecessary therapy, and patients should not take more treatment than they need.

In some cases, a person with GERD symptoms can manage them by taking over-the-counter drugs and making lifestyle changes. This is often safer and less expensive than taking prescription drugs. Some guidelines recommend trying to treat symptoms with an H2 antagonist before using a proton-pump inhibitor because of cost and safety concerns.