Minimally invasive treatments may eliminate the need for more complex surgeries, and can help shorten the patient’s hospital stay length and recovery time.

Treatment Options

  • Medical Therapy
    • Dilation
    • PPI’s: Proton Pump Inhibitors reduced the production of acid in the stomach and decrease the need for dilatation
  • Dilatation
    • In the 16th century, a wand made of wax was used to dilate the esophagus. Currently, dilators are made of balloons or solid plastic.
    • Balloon Dilator: Under visualization by the EGD, a catheter with a balloon on the end is passed through the stricture. The balloon is blown up to open the narrowing
  • Mechanical dilators include:
    • Maloney
      • Flexible, rubber dilators passed from the mouth hrough the stricture in the esophagus
    • Savary – Gilliard Dilators
      • With fluoroscopy, this flexible poly-vinyl chloride dilator is passed through the esophageal stricture
    • Risk of perforation ranges 0.1% to 0.4%
    • To correct the difficulty swallowing, the opening in the esophagus should be at least 12mm
    • The dilation starts with smaller dilators and progressively uses larger dilators. Most patients will experience relief after successful dilatation up to 40 – 54 French, some will even attempt to dilate up to 60 French.
    • The recurrence rate after dilation is 30 – 40% within one year of dilation, even with the aid of concomitant acid suppression
    • The most difficult strictures are due to caustic ingestion or radiation
  • Stents
    Both metallic and non-metallic stents, covered and non-cover stents may be used.

    • Stents are most commonly used in patients with dysphagia due to cancer. Stents are both permanent and removable.
    • Indications:
      • Recurrence after repeated dilations
      • Inoperable malignancy
      • Esophageal fistula
  • Surgery
    • Surgery is not the first line of treatment. It is used after failed medical management.
    • Benign dilatable strictures
      • Esophageal sparing operation
      • Anti-reflux procedure
      • +/- esophageal lengthening procedure as indicated (Collis)
    • Stricture not dilatable
      • Removal of the esophagus is rarely needed to treat a stricture.

Barrett's Esophagus

  • Replacement of the normal esophageal squamous mucosa with columnar epithelium containing goblet cells (metaplasia).
  • Barrett’s predisposes patients to the development of mucosal dysplasia and, ultimately, adenocarcinoma; therefore, should be considered a premalignant (50- to 100-fold increased risk of cancer compared with the general population)
  • The frequency of Barrett’s esophagus has quadrupled over the past few decades, most likely due to improved diagnostic capability with the expansion of flexible endoscopy.

Treatment of Gastroesophageal Reflux

The goal of therapy for GERD is to ameliorate or eliminate the signs and symptoms of GERD and to prevent the development of complications from this disease.

  • Medical treatment has been H2-receptor antagonists or more recently proton pump inhibitors.
  • Surgical treatment is gastric fundoplication which effectively reduces or eliminates reflux symptoms.
  • Both treatments are effective in reducing acid reflux symptoms (>90% symptomatic improvement)
  • Anti-secretory therapy
    • Goal is acid suppression
    • Should be based on the severity of the associated esophagitis.
    • Control the reflux in the hopes of preventing its deleterious effects
    • Allows for more reliable pathologic evaluation of epithelium in looking for dysplasia by decreasing the amount of esophagitis in the field.
    • Currently, proton pump inhibitors (PPIs) are frequently prescribed as the first line of therapy3.
  • pH studies may demonstrate continued reflux even when symptoms resolve.
  • Despite BID proton pump inhibitors, up to 80% of patients continue to demonstrate nocturnal gastric acid reflux.
  • Aggressive use of PPIs has been shown to promote partial regression of esophageal intestinal metaplasia. In a study of patients with Barrett’s esophagus and acid reflux the use of acid suppression with PPI (omeprazole 40 mg) twice a day was compared with H2-blockers (ranitidine 150 mg) twice daily.
    • The PPI (omeprazole) treatment reduced reflux in 99% of patients.
    • Although small, a statistically significant regression in the length and area of Barrett’s was achieved.
    • These findings do not necessarily translate into a decreased risk of cancer.
  • Therefore, the need for continued surveillance is unchanged.
  • There is some data which suggest that the use of antisecretory medical therapy on a long term chronic basis may actually increase the chance of developing cancer. Furthermore, achlorhydria is believed to be a risk factor for the development of adenocarcinoma of the stomach secondary to the propagation of bacteria that produce carcinogenic compounds which flourish with achlorhydria.

Is Barrett’s better treated with surgery than with medical treatment?

  • To date, no randomized trial has definitively proven this.
  • Some studies have shown that control of reflux by fundoplication has can result in regression of Barrett’s esophagus.
  • Additionally, several large non-randomized series have seen a reduction in the overall risk of cancer progression.
  • In a study of endoscopic surveillance for Barrett’s esophagus, no patients who underwent Nissen fundoplication developed dysplasia or adenocarcinoma, whereas some patients in the medically treated patients developed low-grade dysplasia, high-grade dysplasia and some even progressed to adenocarcinoma with medical treatment alone.
  • 5 year follow up after fundoplication for Barrett’s esophagus showed:
    • Regression from low-grade dysplasia to non-dysplastic Barrett’s epithelium in 44% of patients.
    • No development of high-grade dysplasia or carcinoma during 410 patient-years of follow-up.
  • Failure of surgical therapy is due to
  • Technical error in wrap construction. Especially in re-operative cases.
  • Failure to recognize and identify the presence of a shortened esophagus.
  • DeMeester et al. showed a high rate of regression of low-grade dysplasia after an adequate fundoplication. That is not typically seen with maximal medical therapy regimens. Intestinal metaplasia of the esophagus is unlikely to regress after antireflux surgery, although, intestinal metaplasia confined to the cardia may regress.

Conclusions regarding surgery for Barrett’s

  • Surgical correction of the lower esophageal sphincter mechanism may offer the best long-term results for the treatment of patients with Barrett’s esophagus and minimize the risk of progression to cancer.
  • Fundoplication can be performed using minimally invasive techniques.
  • Fundoplication is safe and effective with long-lasting results.
  • This approach should be strongly considered in patients with Barrett’s esophagus.

Treatment Option Dysplasia

High-grade dysplasia has three potential treatment options:

  1. Intensive surveillance (as described above)
  2. Endoscopic ablative therapy
  3. Esophagectomy.
  • Endoscopic ablative therapies:
    • Employ thermal or photochemical energy to destroy the metaplastic esophageal epithelium.
    • The esophageal columnar epithelium may be removed with the aid of:
      • Laser coagulation
      • Electrocautery
      • Heater probe
      • Radiofrequency ablation (RFA)
      • Argon beam coagulator
      • Photodynamic therapy (PDT)
      • Endoscopic Mucosal resection (EMR)
  • Barrett’s esophagus is generally a localized, superficial process for which ablative modalities may represent a potentially viable treatment modality.
  • Because early carcinoma identified in high-grade dysplasia, is typically intramucosal (>90%), so local ablative therapy may be reasonable.
  • Endoscopic Mucosal Resection is an option in patients with neoplastic lesions <2 cm in diameter and with no sign of submucosal infiltration, positive lymph nodes, or distant metastasis, EMR allows for:
    • Complete resection of affected area
    • Preserves architecture of resected specimen
    • Enhanced staging (EUS)
    • 90% local remission
    • Positive deep margins, submucosal invasion → Surgical Resection
    • Relatively new and controversial procedure
  • Photodynamic Therapy
    • Low Grade dysplasis:
      • In a prospective, double blind, randomized placebo-controlled study of PDT for the treatment of Barrett’s esophagus with dysplasia, 18 patients with low-grade dysplasia were randomized to 5-aminolevulinic (5-ALA)-induced PDT versus follow up.
      • In the treatment group: No residual dysplasia was seen within the treatment area of any patient in the PDT group.
      • In the placebo group: Persistent low-grade dysplasia was found in 12/18 patients (p<0.001).
      • There were no short or long term major side effects, and the effects of treatment were maintained for up to 24 months.
  • High Grade dysplasia
    • The majority of patients demonstrate squamous re-epithelialization with no evidence of residual dysplasia.
    • Minor side effects were frequent
    • Esophageal strictures developed in approximately one third of patients.
  • Esophagectomy
    • Ablative therapies demonstrate promise in patients unfit for esophagectomy,
    • However, ablative therapies may not eradicate all of the tissue capable of neoplastic progression and carcinoma has been reported to develop deep to the superficial layers ablated by the phototherapy.
    • Therefore, endoscopic ablative therapies should, at present, be considered only when surgical options are not possible.
    • Esophagectomy is the only therapy guaranteed to prevent the progression of dysplasia to cancer.
    • Almost 40% of patients with high-grade dysplasia are found to be harboring carcinoma in the resected specimen. Fortunately, cancers found at this stage are highly curable, with 5-year survival rates for patients with high-grade dysplasia exceeding 90%.
    • However, Surgery does have risk. Operative mortality rates of 3-12 percent have been reported, but centers with high volume and extensive experience in esophageal resection have minimized the rates of morbidity and mortality, hence improving the risk:benefit ratio.
  • Minimally invasive esophagectomy has been developed as a safe and feasible alternative to the traditional open techniques and represents an ideal approach for this lesion and may help minimize the morbidity associated with esophageal resection. This is further aided by the mucosal localization of disease in Barrett’s esophagus making the operation technically easier to accomplish.

Imaging

  • Esophagram (xray where patient swallows contrast to see the esophagus)
    • Best test to detect luminal show the narrowing of the esophagus
    • Helps to define the location, diameter, length of the lesion to plan treatment.
  • Computed Tomography Scan (CT)
    • CT can help suggest if there is a cancer causing a stricture due to malignancy.
    • Can help with determining the size of the lesion.
    • Can look for spread if there is a cancer
  • Esophagogastroduodenoscopy (EGD)
    • Can diagnose a stricture
    • Can look for evidence of esophagitis
    • Can obtain a biopsy to determine if there is cancer
  • Endoscopic Ultrasound (EUS)
    • EUS is most useful in cases of malignancy.
    • Very accurate in determining depth of invasion and nodal involvement
    • EUS has a sensitivity of 93% and a specificity of 100% when combined with FNA for regional nodal staging
  • Esophageal Manometry
    • Can determine if the muscle in the esophagus works properly.
    • Information about the patient’s esophageal motility can help guide planning for those who will undergo possible anti-reflux surgery.
  • 24 Hour PH
    • Can determine if an excessive amount of acid refluxes from the stomach to the esophagus to determine what operation should be done if indicated.

Pathophysiology

  • Barrett’s esophagus usually arises in the setting of chronic gastroesophageal reflux, with the incidence increasing proportionally to the degree of acid exposure.
  • Bile reflux is a very closely associated with Barrett’s.
  • In Barrett’s, the squamous epithelium in the distal portion of the esophagus is replaced by a columnar epithelium which contains goblet cells.
  • The cuboidal cell population located at the true GE junction is postulated to be the cell of origin of the metaplastic epithelium with the aberrant proliferation of these cells accounting for the development of intestinal metaplasia
  • This cell exhibits markers of both squamous and columnar epithelia and is abundant in microvilli and secretory vesiclesShields
  • Evidence that Barrett’s metaplasia can progress from Dysplasia to Carcinoma cycle is as follows:
    • Metaplastic and dysplastic epithelium are often found adjacent to each other in pathologic specimens.
    • The progression from metaplasia to low-grade dysplasia then high-grade dysplasia and ultimately to carcinoma has been described
  • Helicobacter pylori do not infect the esophagus and is not associated with an increased risk of Barrett’s esophagus or the development of esophageal adenocarcinoma.
    • Postulated inverse relation between strains of Helicobacter pylori infection and risk of esophageal/gastric cardia adenocarcinoma
    • Postulated that H. Pylori may actually protect the esophagus by decreasing gastric acidity and hence the effects of acid reflux

Surveillance

  • Patients with either long segment or short segment Barrett’s require regular endoscopic surveillance
  • The objective is to identify any dysplastic changes, progression of dysplasia or progression to adenocarcinoma. Biopsy results may reveal
  1. No Dysplasia
  2. Inclusive biopsies
  3. Low-Grade Dysplasia
  4. High-Grade Dysplasia
  5. Invasive Adenocarcinoma.
  • High-grade dysplasia is characterized pathologically by enlarged pleomorphic nuclei, loss of nuclear polarity, decreased or absent mucus production and abnormal glandular architecture.
  • When this process penetrates and extends beyond the basement membrane, it is classified as adenocarcinoma.
  • Among patients with Barrett’s esophagus,
    • approximately 15-25% have low-grade dysplasia
    • 5-10% have high-grade dysplasia.
    • Approximately 5-10% of patients will progress from metaplasia to dysplasia per year, and 1% to adenocarcinoma
  • Dysplasia exhibits no gross distinctive features that can be identified visually, therefore, multiple random biopsies from the affected Barrett’s segment should be obtained.
  • 1/3 to 1/2 of patients diagnosed with high-grade dysplasia on biopsy will already have an invasive malignancy if a resection is performed.
    • There should be high suspicion of an underlying cancer if nodularity or stricture are present in patients with high-grade dysplasia.
  • Although the natural history of dysplasia in general is not well understood, high-grade dysplasia is known to be associated with the development of adenocarcinoma.
  • 10-28% of patients progress from high-grade dysplasia to adenocarcinoma within 5 years ranges.
  • Unsuspected cancer was found in 33% to 45% of patients with Barrett’s esophagus who underwent esophagectomy for high-grade dysplasia without pre-operative evidence of carcinoma.
  • Thus in patients with high-grade dysplasia, Endoscopic surveillance is performed every 3-6 months
  • Performing four-quadrant biopsies taken at 1cm intervals to help maximize the sensitivity for the detection of early cancers.
  • Surveillance is controversial because no randomized trial has proven that surveillance improves survival

Guidelines

  • The most comprehensive recommendations are derived from the American College of Gastroenterology Updated guidelines for the diagnosis, surveillance and therapy of Barrett’s esophagus.
  • Treatment of GERD in patients with Barrett’s esophagus should be the same as in patients without Barrett’s esophagus.
  • With the diagnosis of Barrett’s, patients should have surveillance endoscopy with biopsy at intervals based on the presence or absence of dysplasia as well as the grade of dysplasia
    • Without dysplasia, patients should undergo endoscopy every 2-3 years.
    • Low-grade dysplasia, patients should undergo endoscopy at 6 months, at one year and then yearly if there is no progression
    • High-grade dysplasia, confirmation of the pathology should be obtained from an experienced independent pathologist.
      • Once confirmed, patients should undergo either
        • Esophagectomy or
        • Intensive endoscopic surveillance (every three months)
  • The International Society for Diseases of the Esophagus as well as the consensus panel of the Society for Surgery of the Alimentary Tract, the American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy for the management of Barrett’s esophagus all advocate esophagectomy for fit patients with high-grade dysplasia.

Location

  • Pharyngeal
    • Zenker’s
      • Acquired pulsion diverticula of the hypopharynx.
      • Occur between the inferior pharyngeal constrictors and the cricopharyngeus.
        • Killian’s Triangle
      • Discoordination between swallowing and relaxation of the cricopharyngeus (upper esophageal sphincter).
      • Fibrosis of cricopharyngeus over time and decreased upper esophageal sphincter compliance.
      • Results in increased intraluminal pressure during swallowing.
      • Results in herniation of mucosa through a weak area in the posterior wall of the hypopharynx in Killian’s triangle.
  • Body
  • Midthoracic – Parabronchial
    • Usually a traction diverticulum.
    • May be congenital.
    • In some instances it may be associated with esophageal motility disorder, such as Diffuse esophageal spasm and achalasia.
    • Rarely may occur in the setting of esophageal strticture.
  • Epiphrenic
    • Usually a pulsion diverticulum of the distal 10cm of the esophagus.
  • Esophageal Intramural Diverticula (pseudodiverticulosis)
    • Very rare condition.
    • Numerous small outpouchings form in the wall of the esophagus.
    • May range in number from just a few to hundreds of pseudodiverticula.
    • The disease can have segmental distribution or diffusely involve the esophagus.

Summary

  • Barrett’s esophagus is defined by replacement of the normal esophageal squamous mucosa with columnar intestinal metaplasia of the distal esophagus, and carries a 50-100-fold increased risk of esophageal adenocarcinoma compared with the general population.
  • Risk factors for Barrett’s include:
    • Male sex,
    • Smoking history
    • Obesity
    • Caucasian ethnicity
    • Age > 50
    • >5 year history of reflux symptoms.
  • For Barrett’s with either no dysplasia or low-grade dysplasia a fundoplication may be considered. Fundoplication is safe, effective, and can be performed with lasting results using minimally invasive techniques.
  • Medical or surgical antireflux therapy may improve and ameliorate symptoms, but no randomized trials have proven that they reduce the risk of developing esophageal adenocarcinoma.
  • Random sampling of esophageal tissue for dysplasia remains a clinical standard for Barrett’s.
  • No studies have established that endoscopic screening/surveillance programs decrease the rates of death from cancer.
  • Patients with Barrett’s esophagus and high-grade dysplasia, who are fit, should undergo esophagectomy, to help prevent the risk of developing esophageal carcinoma.
  • Endoscopic ablative approaches may represent a reasonable therapeutic alternative for patients that are in poor health, too old or those who refuse esophagectomy.