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Benign Esophageal Disease

Members of the Esophageal team at St John’s Health Center combine highly-developed diagnostic skills with state-of-the-art imaging and functional testing to diagnose diseases of the esophagus. Our multi-disciplinary team offers an integrated, comprehensive approach and minimally invasive surgery to treat esophageal problems.

Esophageal problems treated in the St John’s Esophageal Program include:

  • Achalasia
  • Barrett’s esophagus
  • Esophageal cancer
  • Esophageal diverticula
  • Esophageal stricture
  • Esophageal web
  • Esophagitis
  • Gastro-esophageal reflux disease (GERD)
  • Hiatal hernia
  • Zenker’s diverticulum
Esophageal Stricture

Esophageal strictures are caused by a problem of the esophagus or compression from the outside.
The patient’s symptoms, physical examination, contrast radiographic imaging, endoscopy, and pathology will help us determine the diagnosis.

According to Ferguson, strictures are classified as:
(Evaluation and management of benign esophageal strictures. Ferguson DD. Dis Esophagus. 2005;18(6):359-64.)

  • Simple (not too narrow so the esophagoscope can pass through the narrowing,
    Straight, and short, <2cm)
  • Complex (too narrow so the esophagoscope can pass through the narrowing, angulated, and irregular)
Causes of non-cancerous strictures of the Esophagus
  • Peptic stricture due to stomach acid
  • Schatzki’s ring
  • Motility disorder of esophagus
  • Autoimmune diseases (scleroderma, lupus)
  • Immunocompromise
  • Collagen vascular disease
  • Crohn’s disease
  • Infectious esophagitis,
  • Hiatal hernia
  • Caustic (swallowing toxic liquid)
  • Congenital (born with it)
  • Caused by medicines
  • Reaction to foreign body reaction
  • Radiation therapy
  • Cancer
  • unknown
Peptic Stricture

Is the most common cause of benign esophageal stricture and accounts for approximately 75% of all benign esophageal strictures.

Etiology

  • Acid from the stomach refluxes to the esophagus to cause scarring in the esophagus.

PattersonD J, GrahamD Y, SmithJ L et al. Natural history of benign esophageal stricture treated by dilatation. Gastroenterology 1983; 85: 346–50.
GudaNM, VakilN. Proton pump inhibitors and the time trends for esophageal dilation. Am J Gastroenterol 2004;99:797–800.
MarksR D, RichterJ E. Peptic strictures of the esophagus. Am J Gastroenterol 1993; 88: 1160.

  • A weak lower esophageal sphincter (LES) which should work as a one way valve to allow the passage of food, but prevent the reflux of acid from the stomach back to the esophagus

Ahtaridis G, Snape WJ, Cohen S: Clinical and manometric findings in benign peptic strictures of the esophagus. Dig Dis Sci 1979 Nov; 24(11): 858-61

  • Hiatal hernia (the opening in the diaphragm through which the esophagus is too large).

Ruigómez A, García Rodríguez LA, Wallander MA, Johansson S, Eklund S. Esophageal stricture: incidence, treatment patterns, and recurrence rate. Am J Gastroenterol. 2006 Dec;101(12):2685-92.
MarksRD, ShuklaM. Diagnosis and management of peptic esophageal strictures. Gastroenterologist 1996;4:223–37.
KirschM, BlueM, DesaiRK, et al. Intralesional steroid injections for peptic esophageal strictures. Gastrointest Endosc 1991;37:180–2
SaidA, BrustDJ, GaumnitzEA, et al. Predictors of early recurrence of benign esophageal strictures. Am J Gastroenterol 2003;98:1252–6.

Diangosis

Diagnosis and cause should be established because treatment depends on etiology. Dysphagia is the most common symptom. Frequently, patients will describe a progression of dysphagia from solids to liquids. The presence of dysphagia should prompt an investigative workup to find the cause behind it

Evaluation and management of benign esophageal strictures. Ferguson DD. Dis Esophagus. 2005;18(6):359-64.

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

Kaushik N. Khalid A. Brody D. Luketich JD. McGrath K. Endoscopic ultrasound compared with laparoscopy for staging esophageal cancer. Ann Thorac Surg. 83(6):2000-2, 2007 Jun

  • 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.
Treatment

The goal of treatment is to relieve the dysphagia. Initial therapy is usually esophageal dilatation, but concomitant implementation of medical therapy is essential to promote healing as well as decrease the chance of recurrence. Esophageal resection may be necessary for patients refractory to the above treatments.

Marks RD, Shukla M: Diagnosis and management of peptic esophageal strictures. Gastroenterologist 1996 Dec; 4(4): 223-37
Evaluation and management of benign esophageal strictures. Ferguson DD. Dis Esophagus. 2005;18(6):359-64.

  • Medical Therapy
    • Dilation
    • PPI’s: Proton Pump Inhibitors reduced the production of acid in the stomach and decrease the need for dilatation

stricturesEsophageal stricture: incidence, treatment patterns, and recurrence rate.Ruigómez A, García Rodríguez LA, Wallander MA, Johansson S, Eklund S. Am J Gastroenterol. 2006 Dec;101(12):2685-92.
Marks RD, Richter JE, Rizzo J: Omeprazole versus H2-receptor antagonists in treating patients with peptic stricture and esophagitis. Gastroenterology 1994 Apr; 106(4): 907-15
Smith PM, Kerr GD, Cockel R: A comparison of omeprazole and ranitidine in the prevention of recurrence of benign esophageal stricture. Restore Investigator Group. Gastroenterology 1994 Nov; 107(5): 1312-8

  • 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%

WangY G, TioT L, SoehendraN I. Endoscopic dilation of esophageal stricture without fluoroscopy is safe and effective. World J Gastroenterol 2002; 8: 766–8.
HernandezL J, JacobsonJ W, HarrisM S. Comparison among the perforation rates of Maloney, balloon and Savary dilation of esophageal strictures. Gastrointest Endosc 2000; 51: 460–2.
KarnacI, TanyelF C, BuyukpamukenN et al. Esophageal perforations encountered during the dilation of caustic esophageal strictures. J Cardiovasc Surg 1998; 39: 373–7.
SilvisS E, NebelO, RogersG et al. Endoscopic complications: results of the 1974 American Society of Gastrointestinal Endoscopy survey. JAMA 1976; 235: 928–30.
MandelstamP, SugawaC, SilvisS E et al. Complications associated with esophagogastroduodenoscopy and with esophagaeal dilation. Gastrointest Endosc 1976; 23: 16–29.

  • 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

SaeedZ A, WinchesterC B, FerroP S et al. Prospective randomized comparison of polyvinyl bougies and through-the-scope balloons for dilation of peptic strictures of the esophagus. Gastrointest Endosc 1995; 41: 189–95.
MarksR D, RichterJ E, RizzoJ et al. Omeprazole versus H2-receptor antagonists in treating patients with peptic stricture and esophagitis. Gastroenterology 1994; 106: 907–15.
ChiuY C, HsuC C, ChiuK W et al. Factors influencing clinical application of endoscopic balloon dilation for benign esophageal strictures. Endoscopy 2004; 36: 595–600.
PattersonD J, GrahamD Y, SmithJ L et al. Natural history of benign esophageal stricture treated by dilatation. Gastroenterology 1983; 85: 346–50.
Evaluation and management of benign esophageal strictures. Ferguson DD. Dis Esophagus. 2005;18(6):359-64.

    • 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

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).
  • Found in 7-10% of patients with chronic, severe GERD.
  • 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) Cameron AJ, Lomboy CT, Pera M, et al.: Adenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology 1995;109:1541–1546.
  • 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.
  • The risk of developing adenocarcinoma in patients with Barrett’s esophagus has been estimated to be 0.5% per year Shaheen NJ, Crosby MA, Bozymski EM, et al.: Is there publication bias in reporting cancer risk in Barrett’s esophagus? Gastroenterology 2000;119:333–338.
Clinical Features
  • Risk factors for the development of Barrett’s esophagus are
    Devesa SS, Blot WJ and Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998; 83: 2049-2053.
    Peters JH and DeMeester TR. Esophagus: Anatomy, physiology and gastroesophageal reflux disease. In Surgery: Scientific Principles and Practice –3rd Edition. Greenfield LJ, Mulholland MW, Oldham KT,

    • male sex
    • smoking history
    • obesity
    • caucasian ethnicity
    • age > 50
    • greater than 5-year history of reflux symptoms
    • esophageal motility in Barrett’s
    • weak lower esophageal sphincter allowing for pathologic reflux to occur.
    • esophageal peristalsis often impaired, exacerbating the delay in acid clearance from the distal esophagus.
    • chronic inflammation and fibrosis may lead to esophageal stricture, frequently at the proximal end of the involved segment.
Sign and Symptoms

Most patients with Barrett’s esophagus have a history of heartburn and acid regurgitation.

  • Less frequent symptoms include
    • dysphagia
    • chest pain
    • hematemesis
    • melena
    • cough
    • wheezing
  • Only 4-10% of patients with such clinical symptoms, however, will have Barrett’s esophagus.
  • No symptoms specific for Barrett’s

Lagergren J, Bergstrom R, Lindgren A et al. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999, 340: 825-831.
Peters JH and DeMeester TR. Esophagus: Anatomy, physiology and gastroesophageal reflux disease. In Surgery: Scientific Principles and Practice –3rd Edition. Greenfield LJ, Mulholland MW, Oldham KT,

Pathophysiology

It is believed that Barrett’s epithelium may progress from metaplasia to dysplasia and eventually to carcinoma.

  • 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

Shields HM, Zwas F, Antonioli DA et al. Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett’s epithelium. Dig Dis Sci 1993, 38(1): 97-108.

  • 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

Hameeteman W, Tytgat GN, Houthoff HJ et al. Barrett’s esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 1989, 96(5 Pt 1): 1249-1256.

  • 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

Chow WH, Blaser MJ, Blot WJ et al. An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer res 1998, 58: 588-590.

Diagnosis

The diagnosis of Barrett’s is suggested by finding abnormal columnar epithelium lining the distal esophagus on endoscopy, but must be confirmed by biopsy showing intestinal metaplasia usually with the hallmark presence of mucin-producing goblet cells.

  • One must remember that shorter segments or even just tongues of columnar epithelium may be associated with adenocarcinoma of the gastro-esophageal junction.
    • Traditionally, the diagnosis of Barrett’s was based on the finding of long segments (≥ 3 cm) of columnar epithelium, but intestinal metaplasia has been identified short segments of columnar epithelium, even in the absence of GERD

Spechler SJ, Zeroogian JM, Antonioli DA et al. Prevalence of metaplasia at the gastro-oesophageal junction. Lancet 1994, 344:1533-1536.

  • Barrett’s is classified as follows:
    • Long Segment Barrett’s (≥ 3 cm of specialized intestinal metaplasia)
    • Short Segment Barrett’s (≤ 3 cm of specialized intestinal metaplasia)

Rudolph RE, Vaughan TL, Storer BE et al. Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus. Ann Intern Med 2000, 132: 612-620.

  • Same management for both
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)

Despite the effectiveness in the control of symptoms, neither medical nor surgical anti-reflux therapy have been definitively proven to decrease the risk of esophageal adenocarcinoma

Castell, DO. Medical, surgical and endoscopic treatment of gastoresophageal reflux disease and Barrett’s esophagus. J Clin Gastroenterol 2001; 33(4): 262-266.

  • 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 therapy

Ter Rb, Castell DO. Gastroesophageal reflux disease in patients with columnar-lined esophagus. Gastroenterol Clin North Am 1997, 26: 549-563.

  • 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.

Katz PO, Anderson C, Khouri R, Castell DO. Gastro-oesophageal reflux associated with nocturnal gastric acid breakthrough on proton pump inhibitors. Aliment Pharmacol Ther 1998, 12:1231-1234.

  • 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.

    Peters FTM, Ganesh S, Kuipers EJ et al. Endoscopic regression of Barrett’s oesophagus during omeprazole treatment: a randomized double-blind study. Gut 1999, 45: 489-494.

  • Therefore, the need for continued surveillance is unchanged.

9. Malesci A, Savarino V, Zentilin P, et al.: Partial regression of Barrett’s esophagus by long-term therapy with highdose omeprazole. Gastrointest Endosc 1996;44:700–705.

  • 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 [10].

10. Correa P: Human gastric carcinogenesis: A multistep and multifactorial process—First American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res 1992; 52:6735.

  • Is Barrett’s better treated with surgery than with medical treatment?
    • To date, no randomized trial has definitively proven this

Ye W, Chow WH, Lagergren J, Yin L, Nyren O. Risk of adenocarcinoma of the esophagus and gastric cardia in patients with gastroesophageal reflux diseases after antireflux surgery. Gastroenterology 2001, 121: 1286-1293.
Spechler SJ, Lee E, Ahnen D et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA 2001, 285: 2331-2338.

  • 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

Cameron AJ. Management of Barrett’s esophagus. Mayo Clin Proc 1998, 73(5): 457-461.

  • 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.

Katz D, Rothstein R, Schned A et al. The development of dysplasia and adenocarcinoma during endoscopic surveillance of Barrett’s esophagus. Am J Gastroenterol 1998, 93(4): 536-41.

  • 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

Hofstetter WL, Peters JH, DeMeester TR et al. Long-term outcome of antireflux surgery in patients with Barrett’s esophagus. Ann Surg 2001, 234(4): 532-538.

  • 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

Luketich JD, Grondin SC, Pearson FG. Minimally invasive approaches to acquired shortening of the esophagus: Laparoscopic Collis-Nissen gastroplasty. Sem Thorac Cardiovasc Surg 2000, 12 (3): 173-178.

  • 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
    DeMeester SR and DeMeester TR. The diagnosis and management of Barrett’s esophagus. Advanc Surg 1999, 32, 29-68.
  • Conclusions regarding surgery for Barrett’s
    • Surgical correction of the lower esophageal sphincter mechanism may offer the best long-term results in 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.
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

Reid BJ, Blount PL, Feng Z, Levine DS. Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia. Am J Gastroenterol 2000, 95: 3089-3096.

  • 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

Skacel M, Petras RE, Gramlich TL, Sigel JE, Richter JE, Goldblum JR. The diagnosis of low-grade dysplasia in Barrett’s esophagus and its implications for disease progression. Am J Gastroenterol 2000, 95: 3383-3387.
Buttar NS, Wang KK, Sebo TJ et al. Extent of high-grade dysplasia in Barrett’s esophagus correlates with risk of adenocarcinoma. Gastroenterology 2001, 120:1607-1619.

  • 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.

Altorki NK, Sunagawa M, Little AG, Skinner DB. High-grade dysplasia in the columnar-lined esophagus. Am J Surg 1991;161:97-100.
Falk GW, Rice TW, Goldblum JR, Richter JE. Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett’s esophagus with high-grade dysplasia. Gastrointest Endosc. 1999 Feb;49(2):170-6.

  • 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
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

Peters FP, Kara MA, Rosmolen WD, Aalders MC, Ten Kate FJ, Bultje BC, Krishnadath KK, Fockens P, van Lanschot JJ, van Deventer SJ, Bergman JJ. Endoscopic treatment of high-grade dysplasia and early stage cancer in Barrett’s esophagus. Gastrointest Endosc. 2005 Apr;61(4):506-14.

  • 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.

Ackroyd R, Brown NJ, Davis MF et al. Photodynamic therapy for dysplastic Barrett’s oesophagus: a prospective, double-blind, randomised, placebo controlled trial. Gut 2000; 47: 612-617.

  • 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.

Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett’s esophagus: follow-up in 100 patients. Gastrointest Endosc 1999, 49: 1-7.

  • 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.

Swisher SG, Deford L, Merriman KW et al. Effects of operative volume on morbidity, mortality and hospital use after esophagectomy for cancer. J Thorac Cardiovasc Surg 2000, 119: 1126-1132.

  • 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

Luketich JD, Nguyen NT, Schauer P. Laparoscopic transhiatal esophagectomy for Barrett’s esophagus with high-grade dysplasia. J Soc Lap Surg 1998, 2: 75-77.
Pierre AF, Luketich JD. Technique and role of minimally invasive esophagectomy for premalignant and malignant diseases of the esophagus. Surg Oncol Clin N Am 2002, 11:337-350.
Nguyen NT, Schauer P, Luketich JD. Minimally invasive esophagectomy for Barrett’s esophagus with high-grade dysplasia. Surgery 2000, 127: 284-290.

Guildelines
  • The most comprehensive recommendations are derived from the American College of Gastroenterology Updated guidelines for the diagnosis, surveillance and therapy of Barrett’s esophagus

Sampliner RE: Updated guidelines for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol 2002;97:1888–1895.

  • 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
    Stein HJ. Esophageal Cancer: Screening and surveillance – Results of a consensus conference held at the VIth world congress of the International Society for Diseases of the esophagus. Dis Esophagus 1996, 9 Suppl 1: 3-19.
    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.

The Society for Surgery of the Alimentary Tract (SSAT), American Gastroenterological Association (AGA), American Society for Gastrointestinal Endoscopy (ASGE) Consensus Panel. Management of Barrett’s esophagus. J Gastrointest Surg 2000, 4:115-116.

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,
Esophageal Diverticular

A diverticulum is an outpuching or sac arising from the wall of the esophagus which can contain one or more layers of the wall. Diverticula can be classified based on:

Achkar E. Zenker’s diverticulum. Dig Dis 1998;16(3):144–151.
Montgomery RD, Mendl K, Stephenson SF. Intramural diverticulosis of the oesophagus. Thorax 1975;30(3):278–284.
Hammon JWJr, Rice RP, Postlethwait RW, Young WGJr. Esophageal intramural diverticulosis: a clinical and pathological survey. Ann Thorac Surg 1974;17(3):260–267.

HISTOLOGY

  • Three general types of diverticula exist differentiated by the number of intestinal wall layers involved
    • True Diverticula
      • Contain all layers of the wall
    • False Diverticula (pseudodiverticula)
      • Contain only mucosa and submucosa
    • Intramural Diverticula (pseudodiverticula)
      • Outpouching within the submucosal layer secondary to dilated submucosal excretory ducts

ETIOLOGY

  • Acquired
    • Pulsion Diverticula
      • Secondary to increased intraluminal pressure at a weak point in the wall of the esophagus secondary to either anatomic or functional disturbance. There is a frequent association with esophageal motility disorders such as diffuse esophageal spasm and achalasia.
        • Zenker’s diverticulum
        • Epiphrenic diverticulum

Dodds WJ, Stef JJ, Hogan WJ, Hoke SE, Stewart ET, Arndorfer RC. Radial distribution of esophageal peristaltic pressure in normal subjects and patients with esophageal diverticulum. Gastroenterology 1975;69(3):584–590.
10 Hurwitz AL, Way LW, Haddad JK. Epiphrenic diverticulum in association with an unusual motility disturbance: report of surgical correction. Gastroenterology 1975;68(4 pt 1):795–798.
11 Kaye MD. Oesophageal motor dysfunction in patients with diverticula of the mid-thoracic oesophagus. Thorax 1974;29(6):666–672.
12 Debas HT, Payne WS, Cameron AJ, Carlson HC. Physiopathology of lower esophageal diverticulum and its implications for treatment. Surg Gynecol Obstet 1980;151(5):593–600.

  • TractionDiverticula
    • Secondary to extraluminal traction / pulling on the outside wall of the esophagus secondary to an inflammatory process and fibrosis such as Histoplasmosis or Tuberculosis
      • Midthoracic – Parabronchial location

Ekberg O, Wahlgren L. Dysfunction of pharyngeal swallowing. A cineradiographic investigation in 854 dysphagia patients. Acta Radiol Diagn (Stockh) 1985;26(4):389–395.

  • Intramural Diverticula (pseudodiverticula)
    • Esophageal submucosal glands which are in communication with the esophageal lumen become dilated.
    • Associated with inflammation and thickening of the esophagus, but the pathogenesis of this process is uncertain.
    • Possible etiology may be dilation of the submucosal glands secondary to obstruction by inflammation and debris
    • Stasis and inflammation may also play a role in this disease.

Montgomery RD, Mendl K, Stephenson SF. Intramural diverticulosis of the oesophagus. Thorax 1975;30(3):278–284.
Hammon JWJr, Rice RP, Postlethwait RW, Young WGJr. Esophageal intramural diverticulosis: a clinical and pathological survey. Ann Thorac Surg 1974;17(3):260–267.

  • Very often there is associated esophageal dysmotility and/or strictures within the body of the esophagus.
  • May be a connection with history of corrosive esophageal injury
  • Congenital
  • Present at birth
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

6 Cook IJ, Gabb M, Panagopoulos V, et al. Pharyngeal (Zenker’s) diverticulum is a disorder of upper esophageal sphincter opening. Gastroenterology 1992;103(4):1229–1235.
7 Cook IJ, Blumbergs P, Cash K, Jamieson GG, Shearman DJ. Structural abnormalities of the cricopharyngeus muscle in patients with pharyngeal (Zenker’s) diverticulum. J Gastroenterol Hepatol 1992;7(6):556–562.

  • 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

    D’Ugo D, Cardillo G, Granone P, Coppola R, Margaritora S, Picciocchi A. Esophageal diverticula. Physiopathological basis for surgical management. Eur J Cardiothorac Surg 1992;6(6):330–334.

    •  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
Diagnosis
  • Pharyngeal – Zenker’s
    • Clinical
      • Aspiration pneumonia
      • Halitosis
      • Regurgitation
      • Dysphagia, ranging from globus sensation to obstruction
      • Bleeding
      • Perforation
      • May develop carcinoma within the pouch
    • Physical findings
      • Neck mass if the diverticulum is large
    • Imaging
      • Barium swallow
        • Visualized in the neck / cervical region
        • Lateral views demonstrate the extent of the Zenker’s
      • Computed tomography (CT) scan
        • May show air or fluid filled structure in communication with esophageal lumen
        • Allows for evaluation of surrounding structures in relation to the diverticulum
    • Procedures
      • Esophagogastroduodenoscopy (EGD)
        • Endoscopy is not always necessary in Zenker’s if the diagnosis has already been made by barium swallow.
        • If EGD is to be done, caution is warranted
          • The true esophageal lumen is smaller than the lumen of the Zenker’s
          • To decrease the risk of injury and possible perforation the scope should only be inserted gently and guided in under direct visualization.
  • Midthoracic – Parabronchial
    • Clinical
      • Usually asymptomatic
      • Dysphagia is the most common symptom, but it is often due to an underlying motility disorder rather than the diverticulum itself.
      • Regurgitation
      • Aspiration pneumonia
      • May develop obstruction
      • Bezoar formation has been described
      • May develop carcinoma within the pouch
    • Physical findings
      • Often normal
    • Imaging
      • Barium swallow
        • Visualized in the chest
        • Usually small in size
        • Pouch will usually have a broad base with a wide mouthed pouch
        • Usually located near the tracheal bifurcation
      • Computed tomography (CT) scan may be done,
        • Will show air or fluid filled structure in communication with esophageal lumen
        • Allows for identification of enlarged or calcified mediastinal nodes
        • Allows for evaluation of surrounding mediastinal structures in relation to the diverticulum
    • Procedures
      • Esophagogastroduodenoscopy (EGD)
        • Allows for visual inspection of the esophagus
        • Will help in identifying any erosion or other endoluminal pathology that may be associated with or the cause of the diverticulum.
        • Helpful in evaluation the pouch and ruling out a carcinoma within the diverticulum
      • Esophageal manometry
        • Helpful in diagnosing an esophageal motility disorder that may be present.
        • Esophageal motility disorder may be the underlying cause of the diverticulum.
        • Manometry is useful in planning for surgical intervention
  • Epiphrenic
    • Clinical
      • Usually asymptomatic
      • Dysphagia is the most common symptom, but it is often due to an underlying motility disorder, rather than the diverticulum itself.
      • Regurgitation
      • Aspiration pneumonia
      • May develop obstruction
      • Bezoar formation has been described
      • May develop carcinoma within the pouch
    • Physical findings
      Often normal
    • Imaging
      • Barium swallow
        • Visualized near the diaphragm
        • Usually a large globular pouch
        • May see abnormal esophageal contractions
      • Computed tomography (CT) scan may be done,
        • Will show air or fluid filled structure in communication with esophageal lumen
        • Allows for evaluation of surrounding structures in relation to the diverticulum
    • Procedures
      • Esophagogastroduodenoscopy (EGD)
        • Allows for Visual inspection of the esophagus
        • Will help in identifying any erosion or other endoluminal pathology that may be associated with or the cause of the diverticulum.
        • Helpful in evaluation the pouch and ruling out a carcinoma within the diverticulum
      • Esophageal manometry
        • Helpful in diagnosing an esophageal motility disorder that may be present.
          • Esophageal motility disorder may be the underlying cause of the diverticulum.
          • Manometry is useful in planning for surgical intervention
  • Intramural pseudodiverticulosis
    • Clinical
      • Dysphagia is the most common symptom.
      • May have esophageal dysmotility
      • May be associated with esophageal stricture
    • Physical findings
      • Often normal
    • Imaging
      • Barium swallow
        • May be segmental or diffusely distributed throughout the esophagus
        • Will see numerous small diverticula lining the esophageal wall
    • Procedures
      • Esophagogastroduodenoscopy (EGD)
        • Openings of the small diverticula are usually not visible on endoscopy

Mahajan SK, Warshauer DM, Bozymski EM: Esophageal intramural pseudo-diverticulosis: endoscopic and radiologic correlation. Gastrointest Endosc 1993 Jul-Aug; 39(4): 565-7[Medline].
Medeiros LJ, Doos WG, Balogh K: Esophageal intramural pseudodiverticulosis: a report of two cases with analysis of similar, less extensive changes in “normal” autopsy esophagi. Hum Pathol 1988 Aug; 19(8): 928-31

Congenital Esophageal Duplication And Duplication Cyst

ETIOLOGY

  • Originate from the primitive foregut
    • The defect responsible for esophageal cysts is the failure of proper development of the posterior division of the primitive foregut.
  • Esophageal cysts are the second most common benign lesion of the esophagus
  • Account for up to 20% of benign esophageal lesions.
  • The cysts are comprised of
    • Acquired epithelial cysts
      • A minority of the cysts.
    • Congenital Foregut Cyst
      • Represent majority of cases
      • Lined by squamous, respiratory or columnar epithelium, may contain smooth muscle, cartilage or fat

Nobuhara KK, Gorski YC, La Quaglia MP, Shamberger RC. Bronchogenic cysts and esophageal duplications: common origins and treatment. J Pediatr Surg. 1997 Oct;32(10):1408-13.
59 Salo JA, Ala-Kulju KV. Congenital esophageal cysts in adults. Ann Thorac Surg 1987;44(2):135–138

  • Esophageal duplication cyst
    • A type of congenital foregut cyst
    • Lined by squamous epithelium
    • May contain gastric mucosa

Hover AR, Brady CE 3rd, Williams JR, Stewart DL, Christian C. Multiple retention cysts of the lower esophagus. J Clin Gastroenterol. 1982 Jun;4(3):209-12.
44 Christensen J, Wingate DL, Gregory RA. A Guide to Gastrointestinal Motility. Oxford: Butterworth-Heinemann, 1983.
59 Salo JA, Ala-Kulju KV. Congenital esophageal cysts in adults. Ann Thorac Surg 1987;44(2):135–138

  • Can be attached either to the esophagus or to the tracheobronchial tree.
  • Develop independently from the native esophagus
  • Usually does not have continuity with the native esophagus.
  • May be associated with other congenital malformations.
    • Vertebral abnormalities\
    • Spinal cord abnormalities
    • Tracheoesophageal fistula
    • Esophageal atresia distal to the duplication
    • Other gastrointestinal duplications, more often small bowel.

56 Nakao A, et al. Rapidly enlarging esophageal duplication cyst. J Gastroenterol 1999;34(2):246–249. 60Stringer MD, et al. Management of alimentary tract duplication in children. Br J Surg 1995;82(1):74–78.

CLINICAL

  • Most are diagnosed in childhood, as most children are symptomatic
  • May present in the first year of life with respiratory compromise secondary to mass effect from the cyst
  • Cysts may become symptomatic in adulthood
    • Usually located in the right posterior mediastinum.
    • Chest pain or chest discomfort is most common.
    • Cough, stridor, tachypnea and other respiratory complaints due to compression from mass
    • Hematemesis can occur if there is gastric epithelium within the cyst.
    • Dysphagia may occur.
    • Cardiac arrhythmias may occur due to compression
    • Other complications may include
      • Infarction
      • Rupture
      • Dysplasia and malignant degeneration60, 61

60Stringer MD, et al. Management of alimentary tract duplication in children. Br J Surg 1995;82(1):74–78. 61 Neo EL, Watson DI, Bessell JR. Acute ruptured esophageal duplication cyst. Dis Esophagus 2004;17(1):109–111.

DIAGNOSIS

  • History and appropriate imaging will usually result in the diagnosis.
  • Imaging
    • Chest X-Ray:
      • May demonstrate a soft tissue mass or a cystic structure within the mediastinum with possible shift.
    • Barium swallow:
      • May show esophageal compression.
      • May detect tubular esophageal duplication if I has a communication with the esophagus
      • It may miss an esophageal cyst with no communication with the esophageal lumen.

61 Neo EL, Watson DI, Bessell JR. Acute ruptured esophageal duplication cyst. Dis Esophagus 2004;17(1):109–111

  • Computed Tomography Scan (CT):
    • The study of choice
    • Allows for diagnosis
    • Usually identify a cystic fluid filled mass intimately related to the esophagus
    • Helps aid in operative preparation, by delineating the anatomy of the mass and its surrounding structures prior to surgical resection,
  • Technetium scan
    • The addition of a nuclear (technetium) scan may help identify ectopic gastric mucosa within the cyst.
  • Magnetic Resonance Imaging (MRI):
    • May be helpful in diagnosing esophageal cysts.
  • Endoscopy demonstrates extrinsic compression with intact mucosa.
  • Endoscopic ultrasonography reveals a cystic, filled structure in connection with the esophagus.
  • Procedures
    • Esophagoscopy:
      • Need to rule out intraluminal pathology
      • If any lesion or abnormality is seen, it should be biopsied to evaluate for possible malignancy.
    • Endoscopic Ultrasound (EUS):
      • Help delineate the intramural or extraesophageal extent of the cyst.
      • Distinguish between solid and cystic masses

TREATMENT

  • Removal of all discovered cysts is advocated, as most will eventually be symptomatic by adulthood
  • Definitive treatment involves complete surgical resection of the duplication, even for asymptomatic cysts.St-Georges R, Deslauriers J, Duranceau A, Vaillancourt R, Deschamps C, Beauchamp G, Pagé A, Brisson J. Clinical spectrum of bronchogenic cysts of the mediastinum and lung in the adult. Ann Thorac Surg. 1991 Jul;52(1):6-13.
  • Simple cysts may be enucleated
  • Duplications need to be excised.
  • Traditionally a posterolateral thoracotomy was employed for access to the lesion
  • Currently, with the advent of minimally invasive techniques, the use of video-assisted thoracoscopic surgery (VATS) has become the procedure of choice in the approach to these lesions.
  • Transesophageal endoscopic drainage has been described, but this procedure does not address the lining of the cyst and the recurrence rate is high.

Kuhlman JE, Fishman EK, Wang KP, Siegelman SS. Esophageal duplication cyst: CT and transesophageal needle aspiration. AJR Am J Roentgenol. 1985 Sep;145(3):531-2.