Many different topical and systemic medications have been studied, including anti-inflammatories, antimycotics (target Candida species), carotenoids (precursors to vitamin A, e.g. beta carotene), retinoids (drugs similar to vitamin A), and cytotoxics, but none have evidence that they prevent malignant transformation in an area of leukoplakia.Vitamins C and E have also been studied with regards a therapy for leukoplakia. Some of this research is carried out based upon the hypothesis that antioxidant nutrients, vitamins and cell growth suppressor proteins (e.g. p53) are antagonistic to oncogenesis. High doses of retinoids may cause toxic effects. Other treatments that have been studied include photodynamic therapy.

Surgical removal of the lesion is the first choice of treatment for many clinicians. However, the efficacy of this treatment modality cannot be assessed due to insufficient available evidence. This can be carried out by traditional surgical excision with a scalpel, with lasers, or with eletrocautery or cryotherapy. Often if biopsy demonstrates moderate or severe dysplasia then the decision to excise them is taken more readily. Sometimes white patches are too large to remove completely and instead they are monitored closely. Even if the lesion is completely removed, long term review is still usually indicated since leukoplakia can recur, especially if predisposing factors such as smoking are not stopped.

Esophageal webs and rings can be treated with endoscopic dilation.

Asymptomatic Schatzki rings seldom worsen over time, and need no treatment.

Symptomatic Schatzki rings may be treated with esophageal dilatation, using bougie or balloon dilators. These have been found to be equally effective. Bougie dilatation involves passage of long dilating tubes of increasing size down the esophagus to stretch the area of narrowing, either over a guidewire passed into the stomach by endoscopy (the "Savary-Gillard" system) or using mercury-weighted dilators (the "Maloney" system). This is usually done with intravenous sedation to reduce discomfort. Dilatation can produce some temporary irritation. A short course of proton pump inhibitor therapy may decrease aggravation by stomach acid reflux into the esophagus. The duration of the benefit of dilation varies, but may be from months to years. Dilation may be repeated if narrowing recurs.

Usually no treatment is indicated for clinically asymptomatic cervical ectropions. Hormonal therapy may be indicated for symptomatic erosion. If it becomes troublesome to the patient, it can be treated by discontinuing oral contraceptives, cryotherapy treatment, or by using ablation treatment under local anaesthetic. Ablation involves using a preheated probe (100 °C) to destroy 3–4 mm of the epithelium. In post-partum erosion, observation and re-examination are necessary for 3 months after labour.

Many people with Barrett's esophagus do not have dysplasia. Medical societies recommend that if a patient has Barrett's esophagus, and if the past two endoscopy and biopsy examinations have confirmed the absence of dysplasia, then the patient should not have another endoscopy within three years.

Endoscopic surveillance of people with Barrett's esophagus is often recommended, although little direct evidence supports this practice. Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction).

The risk of malignancy is highest in the U.S. in Caucasian men over fifty years of age with more than five years of symptoms. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). Although in the past physicians have taken a watchful waiting approach, newly published research supports consideration of intervention for Barrett's esophagus. Balloon-based radiofrequency ablation, invented by Ganz, Stern, and Zelickson in 1999, is a new treatment modality for the treatment of Barrett's esophagus and dysplasia, and has been the subject of numerous published clinical trials. The findings demonstrate radiofrequency ablation has an efficacy of 90% or greater with respect to complete clearance of Barrett's esophagus and dysplasia with durability up to five years and a favorable safety profile.

Proton pump inhibitor drugs have not been proven to prevent esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. Additionally, a recent five-year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor. There is presently no reliable way to determine which patients with Barrett esophagus will go on to develop esophageal cancer, although a recent study found the detection of three different genetic abnormalities was associated with as much as a 79% chance of developing cancer in six years.

Endoscopic mucosal resection has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.

In a variety of studies, nonsteroidal anti-inflammatory drugs (NSAIDS), like aspirin, have shown evidence of preventing esophageal cancer in people with Barrett's esophagus. However, none of these studies have been randomized, placebo-controlled trials, which are considered the gold standard for evaluating a medical intervention. In addition, the best dose of NSAIDs for cancer prevention is not yet known.

The current first-line treatment is fluconazole, 200 mg. on the first day, followed by daily dosing of 100 mg. for at least 21 days total. Treatment should continue for 14 days after relief of symptoms.

Other therapy options include:

- nystatin is not an effective treatment for esophageal candidiasis. It can be used as (swish, do not swallow) treatment for oral candidiasis that occurs with the use of asthma pumps.

- other oral triazoles, such as itraconazole

- caspofungin, used in refractory or systemic cases

- amphotericin, used in refractory or systemic cases

Patients generally respond well to treatment. Iron supplementation usually resolves the anemia, and corrects the glossodynia (tongue pain).

If small and asymptomatic, no treatment is necessary. Larger, symptomatic cases of Zenker's diverticulum have been traditionally treated by neck surgery to resect the diverticulum and incise the cricopharyngeus muscle. However, in recent times non-surgical endoscopic techniques have gained more importance (as they allow for much faster recovery), and the currently preferred treatment is endoscopic stapling (i.e. diverticulotomy with staples ). This may be performed through a diverticuloscope. Other methods include fibreoptic diverticular repair.

Other non-surgical treatment modalities also exist, such as endoscopic laser, which recent evidence suggests is less effective than stapling.

There is risk of perforation of the esophagus with the use of dilators for treatment. Furthermore, it is one of the risk factors for developing squamous cell carcinoma of the oral cavity, esophagus, and hypopharynx.

If it is caused by esophagitis, in turn caused by an underlying infection, it is commonly treated by treating the infection (typically with antibiotics). In order to open the stricture, a surgeon can insert a bougie – a weighted tube used to dilate the constricted areas in the esophagus. It can sometimes be treated with other medications. For example, an H2 antagonist (e.g. ranitidine) or a proton-pump inhibitor (e.g. omeprazole) can treat underlying acid reflux disease.

Currently, there is no direct treatment for AEN. Only treatment is for the underlying main diseases or conditions. Appropriate hydration is set. Antacids are also added for further recovery support. Common support drugs of antacids are either H receptor antagonists, and/or a proton pump inhibitor. Sucralfate was used as an option. Parenteral nutrition greatly increased chance of recovery. An esophagectomy can be issued if the disorder is severe enough.

Localised disease (carcinoma-in-situ) and the precursor condition, anal intraepithelial neoplasia (anal dysplasia or AIN) can be ablated with minimally invasive methods such as Infrared Photocoagulation.

Previously, anal cancer was treated with surgery, and in early-stage disease (i.e., localised cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the internal and external anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies.

Current gold-standard therapy is chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy consists of continuous infusion 5-FU over four days with bolus mitomycin given concurrently with radiation. 5-FU and cisplatin are recommended for metastatic anal cancer.

10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. Median survival rates for patients with distant metastases ranges from 8 to 34 months.

In patients who have no response to medical or endoscopic therapy, surgery can be performed. A Heller myotomy involves an incision to disrupt the LES and the myenteric plexus that innervates it. The Heller myotomy is used as a final treatment option in patients who do not respond to other therapies.

Several drugs are used to treat DES, including nitroglycerin, hyoscine butylbromide, calcium channel blockers, hydralazine, and anti-anxiety medications. Acid suppression therapy, such as proton pump inhibitors, are often the first line therapy. Botulinum toxin, which inhibits acetylcholine release from nerve endings, injected above the lower esophageal sphincter may also be used in the treatment of DES. Small studies have suggested benefit from endoscopic balloon dilation in certain patients, but all of the above have a low percentage of success in treating the condition; whilst the treatments work in some sufferers, it does not work for everyone. In extremely rare cases, surgery may be considered.

Nutcracker esophagus is a benign, nonprogressive condition, meaning it is not associated with significant complications. Patients are usually reassured by their physicians that the disease is unlikely to worsen. However, the symptoms of chest pain and dysphagia may be severe enough to require treatment with medications, and rarely, surgery.

The initial step of treatment focuses on reducing risk factors. While weight reduction may be useful in reducing symptoms, the role of acid suppression therapy to reduce esophageal reflux is still uncertain. Very cold and very hot beverages may trigger esophageal spasms.

Medical therapy for nutcracker esophagus includes the use of calcium-channel blockers, which relax the lower esophageal sphincter (LES) and palliate the dysphagia symptoms. Diltiazem, a calcium-channel blocker, has been used in randomized control studies with good effect. Nitrate medications, including isosorbide dinitrate, given before meals, may also help relax the LES and improve symptoms. The inexpensive generic combination of belladonna and phenobarbital (Donnatal and other brands) may be taken three times daily as a tablet to prevent attacks or, for patients with only occasional episodes, as an elixir at the onset of symptoms. Phosphodiesterase inhibitors, such as sildenafil, can be given to reduce symptoms, particularly pain, but small trials have not been able to demonstrate clinical improvement. Finally, trazodone, an antidepressant that reduces visceral sensitivity, has also been shown to reduce chest pain symptoms in patients with nutcracker esophagus.

Endoscopic therapy with botulinum toxin, known also as Botox, can also be used to improve dysphagia which stabilizes unintentional weight loss, but the effect has limited effect on other symptoms, including pain, while also being a temporary treatment lasting a few weeks. Finally, pneumatic dilatation of the esophagus, which is an endoscopic technique where a high-pressure balloon is used to stretch the muscles of the LES, can be performed to improve symptoms, but again no clinical improvement is seen in regards to motility.

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 be recommended only 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. A wedge pillow that elevates the head may inhibit gastroesophageal reflux during sleep. Stopping smoking and not drinking alcohol do not appear to result in significant improvement in symptoms. Although moderate exercise may improve symptoms in people with GERD, vigorous exercise may worsen them.

The treatments for GERD include lifestyle modifications, medications, and possibly surgery. Initial treatment is frequently with a proton-pump inhibitor such as omeprazole.

Both before and after treatment, achalasia patients may need to eat slowly, chew very well, drink plenty of water with meals, and avoid eating near bedtime. Raising the head off the bed or sleeping with a wedge pillow promotes emptying of the esophagus by gravity. After surgery or pneumatic dilatation, proton pump inhibitors are required to prevent reflux damage by inhibiting gastric acid secretion, and foods that can aggravate reflux, including ketchup, citrus, chocolate, alcohol, and caffeine, may need to be avoided.

Drugs that reduce LES pressure are useful. These include calcium channel blockers such as nifedipine and nitrates such as isosorbide dinitrate and nitroglycerin. However, many patients experience unpleasant side effects such as headache and swollen feet, and these drugs often stop helping after several months.

Botulinum toxin (Botox) may be injected into the lower esophageal sphincter to paralyze the muscles holding it shut. As in the case of cosmetic Botox, the effect is only temporary and lasts about 6 months. Botox injections cause scarring in the sphincter which may increase the difficulty of later Heller myotomy. This therapy is recommended only for patients who cannot risk surgery, such as elderly people in poor health. Pneumatic dilatation has a better long term effectiveness than botox.

Forms of endoscopic therapy have been used for stage 0 and I disease: endoscopic mucosal resection (EMR) and mucosal ablation using radiofrequency ablation, photodynamic therapy, Nd-YAG laser, or argon plasma coagulation.

Laser therapy is the use of high-intensity light to destroy tumor cells while affecting only the treated area. This is typically done if the cancer cannot be removed by surgery. The relief of a blockage can help with pain and difficulty swallowing. Photodynamic therapy, a type of laser therapy, involves the use of drugs that are absorbed by cancer cells; when exposed to a special light, the drugs become active and destroy the cancer cells.

The patient is generally sent for a GI, pulmonary, or ENT, depending on the suspected underlying cause. Consultations with a speech therapist and registered dietitian nutritionist (RDN) are also needed, as many patients may need dietary modifications such as thickened fluids.

Treatment is best managed by a multidisciplinary team covering the various specialties involved. Adequate nutrition must be assured, and appropriate dental care is essential. Factors that influence treatment decisions include the stage and cellular type of cancer (EAC, ESCC, and other types), along with the person's general condition and any other diseases that are present.

In general, treatment with a curative intention is restricted to localized disease, without distant metastasis: in such cases a combined approach that includes surgery may be considered. Disease that is widespread, metastatic or recurrent is managed palliatively: in this case, chemotherapy may be used to lengthen survival, while treatments such as radiotherapy or stenting may be used to relieve symptoms and make it easier to swallow.

Treatments for the condition vary depending on its severity. The most immediate and effective treatment in the majority of cases is a surgical repair to close the fistula/s and reconnect the two ends of the esophagus to each other. Although this is usually done through an incision between the ribs on right side of the baby, a technique using three small incisions (thoracoscopy) is being used at some centers. In a minority of cases, the gap between upper and lower esophageal segments may be too long to bridge. In some of these so-called long gap cases, though, an advanced surgical treatment developed by John Foker, MD, may be utilized to elongate and then join together the short esophageal segments. Using the Foker technique, surgeons place traction sutures in the tiny esophageal ends and increase the tension on these sutures daily until the ends are close enough to be sewn together. The result is a normally functioning esophagus, virtually indistinguishable from one congenitally well formed. Unfortunately, the results have been somewhat difficult to replicate by other surgeons and the need for multiple operations has tempered enthusiasm for this approach.

The optimal treatment in cases of long gap esophageal atresia remains controversial. Traditional surgical approaches include gastrostomy followed by gastric pull-up, colonic transposition and jejunum transposition. Gastric pull-up has been the preferred approach at many specialized centers, including Great Ormond Street (London) and Mott Children's Hospital (Ann Arbor). Gastrostomy, or G-tube, allows for tube feedings into the stomach through the abdominal wall. Often a cervical esophagostomy will also be done, to allow the saliva which is swallowed to drain out a hole in the neck. Months or years later, the esophagus may be repaired, sometimes by using a segment of bowel brought up into the chest, interposing between the upper and lower segments of esophagus.

Post operative complications sometimes arise, including a leak at the site of closure of the esophagus. Sometimes a stricture, or tight spot, will develop in the esophagus, making it difficult to swallow. This can usually be dilated using medical instruments. In later life, most children with this disorder will have some trouble with either swallowing or heartburn or both. Esophageal dismotility occurs in 75-100% of patients.

Tracheomalacia—a softening of the trachea, usually above the carina (carina of trachea), but sometimes extensive in the lower bronchial tree as well—is another possible serious complication. Even after esophageal repair (anastomosis) the relative flaccidity of former proximal pouch (blind pouch, above) along with esophageal dysmotility can cause fluid buildup during feeding. Owing to proximity, pouch ballooning can cause tracheal occlusion. Severe hypoxia ("dying spells") follows and medical intervention can often be required.

A variety of treatments for tracheomalacia associated with esophageal atresia are available. If not severe, the condition can be managed expectantly since the trachea will usually stiffen as the infant matures into the first year of life. When only the trachea above the carina is compromised, one of the "simplest" interventions is aortopexy wherein the aortic loop is attached to the rear of the sternum, thereby mechanically relieving pressure from the softened trachea. An even simpler intervention is stenting. However, epithelial cell proliferation and potential incorporation of the stent into the trachea can make subsequent removal dangerous.