Esophageal Neoplasms


Barrett’s Esophagus

  1. Pathophysiology
    • intestinal columnar epithelium replaces the stratified squamous epithelium of the esophagus
    • chronic reflux injures the squamous epithelium and promotes repair through columnar metaplasia
    • represents end-stage GERD
    • continued reflux of acid (and bile) results in progression to low-grade and then high-grade dysplasia
    • the chance of developing esophageal adenocarcinoma is 0.25% per year in patients without dysplasia, and 4% - 8% per year in patients with high-grade dysplasia
    • overall, 10% of patients with GERD develop Barrett’s esophagus

    Barrett's Esophagus
  2. Diagnosis
    • made by endoscopy and pathology
    • any length of endoscopically visible columnar epithelium above the GEJ that is confirmed histologically to be within the esophagus is defined as Barrett’s esophagus

  3. Treatment of Nondysplastic Barrett’s Esophagus
    1. Medical Management
      • treatment goal is to control GERD effectively
      • PPIs are the first-line treatment
      • annual surveillance endoscopy is usually recommended, but there is little evidence that it is beneficial

    2. Antireflux Surgery
      • effective treatment for most patients with GERD and BE
      • may produce higher rates of BE regression than medical therapy
      • however, the long-term effects in preventing esophageal adenocarcinoma are controversial

    3. Endoscopic Therapies
      • radiofrequency ablation and photodynamic therapy can eradicate BE cells and promote reversion back to squamous epithelium
      • no data to suggest that endoscopic ablative therapies reduce cancer risk or are more cost effective than periodic long-term endoscopic surveillance

  4. Treatment of Dysplastic Barrett’s Esophagus
    1. Low-Grade Dysplasia
      • medical therapy or antireflux surgery are effective treatment options for GERD
      • endoscopic management (ablation or resection) is usually recommended for dysplasia, but surveillance is another option
      • if endoscopic surveillance is chosen, then it should be repeated every 6 – 12 months, with 4-quadrant biopsies taken at 1 cm intervals

    2. High-Grade Dysplasia
      1. Endoscopic Eradication
        • obvious mucosal abnormalities should be excised with endoscopic resection
        • radiofrequency ablation (RFA) is then used to ablate the remaining metaplastic epithelium

      2. Esophagectomy
        • most patients with high-grade dysplasia are now treated endoscopically
        • transhiatal esophagectomy is the most common surgical procedure chosen
        • minimally invasive approaches, and vagal-sparing techniques, are becoming more common

    3. Intramucosal Carcinoma
      • endoscopic resection allows for histologic evaluation
      • if there is no invasion of the submucosa, then endoscopic therapy is usually the preferred approach
      • submucosal invasion will require esophagectomy

Esophageal Carcinoma

  1. Epidemiology
    1. Squamous Cell Carcinoma
      • accounts for the great majority of cases worldwide
      • very high incidence in Northern Iran and certain areas of South Africa, China, and Kazakhstan
      • etiologic agents include additives to local foodstuffs (nitroso compounds) and ingestion of hot liquids
      • in western countries, smoking and alcohol abuse are strongly linked
      • premalignant conditions include achalasia, caustic esophageal burns (lye), and radiation esophagitis
      • typically found in the upper and middle thirds of the esophagus

    2. Adenocarcinoma
      • once rare, but is now the fastest growing cancer in the United States
      • GERD and obesity are felt to play major etiologic roles
      • now accounts for 60% - 70% of esophageal cancers in the U.S.
      • originates in metaplastic columnar-lined epithelium (Barrett’s Esophagus) which occurs in 10% of patients with GERD
      • Barrett’s esophagus is associated with a 30 - 40X increased risk of esophageal adenocarcinoma

  2. Clinical Manifestations
    • early-stage tumors may be asymptomatic and are usually found on routine endoscopic surveillance for Barrett’s esophagus
    • dysphagia and weight loss are the most common symptoms, and indicate advanced disease
    • odynophagia may also be present
    • extension of the tumor into the tracheobronchial tree can result in a tracheoesophageal fistula, with symptoms of choking, coughing, and aspiration pneumonia
    • paralysis of a recurrent laryngeal may occur as a result of local invasion

  3. Diagnosis and Staging
    1. Esophagram
      • recommended for any patient presenting with dysphagia
      • provides an overview of anatomy and function
      • can distinguish between extrinsic and intrinsic compression
      • classic finding of cancer is an apple core lesion

      Esophagram showing a Malignant Stricture
    2. Endoscopy
      • allows biopsy of tumors
      • can determine the distance of the tumor from the incisors and GEJ
      • can assess for gastric cardia involvement and the suitability of the stomach as a replacement conduit

    3. CT Scan
      • useful to evaluate the extent of the tumor and its relationships with surrounding structures, regional nodal status, and metastatic disease to the liver and lungs
      • only 57% accurate for T staging, 74% for N staging, and 83% for M staging

    4. PET-CT Scan
      • probably the single best systemic staging tool
      • overall accuracy for staging regional nodes and presence of distant disease is higher than CT scanning

    5. Endoscopic Ultrasound (EUS)
      • can determine the depth and length of the tumor, status of regional nodes
      • EUS-FNA provides the most accurate nodal staging information
      • overall T-stage accuracy is 85%, but is more accurate for increasing T stage

    6. Endoscopic Mucosal Resection
      • for early-stage tumors, allows for accurate histologic distinction between mucosal (T1a) and submucosal (T1b) tumors
      • since esophageal lymphatics are in the submucosa, T1a tumors can be treated endoscopically, while T1b tumors require surgical resection

    7. Other Staging Tools
      • bronchoscopy is used to rule out tracheal invasion or tracheoesophageal fistula in symptomatic patients
      • mediastinoscopy may be used to biopsy suspicious nodes not amenable to EUS-FNA
      • laparoscopy or thoracoscopy may be used to evaluate possible metastatic lesions in selected patients

    8. Cancer-Related Biomarkers
      • beginning to find a role in esophageal cancer
      • HER2 overexpression correlates with cancer progression and may be amenable to treatment with trastuzumab

  4. Staging
    • precise staging allows for the most appropriate treatment
    • tumor depth (T stage) directly relates to lymph node involvement
    • T1a and superficial T1b tumors rarely metastasize to regional nodes
    • deep T1b tumors (>50% of the submucosa invaded) are metastatic to regional nodes ~ 40% of the time
    • T2 tumors involve the muscularis propria
    • T3 tumors involve the adventitia
    • T4 tumors locally invade other mediastinal structures

  5. Anatomy
    1. Arterial Supply
      • segmental
      • cervical esophagus receives its blood supply from the superior and inferior thyroid arteries
      • thoracic esophagus receives blood from 4 to 6 esophageal aortic arteries, as well as from branches of the bronchial and intercostal arteries
      • abdominal esophagus receives blood from the left gastric artery and inferior phrenic arteries

    2. Venous Drainage
      • is first into the submucosal venous plexus and then into the inferior thyroid vein (cervical esophagus); bronchial, azygos, and hemiazygos veins (thoracic esophagus); and the coronary vein (abdominal esophagus)

    3. Lymphatic Drainage
      • esophagus has an extensive lymphatic drainage
      • lymphatics are located primarily in the submucosa

        • Lymphatic Drainage of the Esophageal Wall
      • lymph flow is in the longitudinal direction, which facilitates spread along the esophageal wall
      • lymph flow in the upper 2/3 of the esophagus is upwards (internal jugular nodes, paratracheal and mediastinal nodes)
      • lymph flow in the lower 1/3 of the esophagus is downwards (inferior paraesophageal nodes, left gastric nodes, celiac artery nodes)

      Lymphatic Drainage of the Esophagus
  6. Treatment
    1. Management Considerations
      1. Histology
        • squamous cell cancer (SCC) is more responsive to chemoradiation than adenocarcinoma
        • SCCs are more likely to have a complete clinical response to neoadjuvant chemoradiation, making the need for surgical intervention uncertain

      2. Tumor Depth
        • tumors confined to the mucosa (T1a) can be treated with endoscopic mucosal resection
        • T2, T3 tumors should probably receive neoadjuvant chemoradiation

      3. Regional Nodal Status
        • patients with known nodal disease, or those at high risk because of tumor depth, should probably receive neoadjuvant chemoradiation

      4. Systemic Disease
        • require definitive chemoradiation
        • if totally obstructed, can consider a palliative resection if life expectancy is reasonable

      5. Patient Condition
        • age, comorbidities, nutritional status affect the ability of patients to tolerate treatment
        • most patients need preoperative pulmonary function and cardiac stress testing
        • greater than a 10% weight loss or albumen level < 3.4 are associated with increased surgical complications
        • nutritional status can be improved with an esophageal stent or feeding jejunostomy tube

    2. Neoadjuvant Treatment
      • should be considered for all tumors at high risk for nodal metastasis (deeper than deep T1b)
      • near consensus that surgery alone is inadequate for regionally advanced cancers
      • concurrent chemoradiation is better than sequential chemotherapy and radiation
      • one unanswered question is whether to proceed with an esophagectomy in a patient who has had a complete clinical response to chemoradiation

    3. Surgical Resection
      1. Transhiatal Esophagectomy (THE)
        • performed through an upper midline abdominal incision and a cervical incision, avoiding a thoracotomy
        • entire thoracic esophagus is resected
        • stomach is used as the replacement organ in most cases
        • the anastomosis is placed in the neck, avoiding the complications of an intrathoracic leak and gastroesophageal reflux
        • a pyloromyotomy and feeding jejunostomy are performed routinely
        • this operation has been criticized as violating oncologic surgical principles by omitting a formal lymph node dissection in potentially curable patients
        • a laparoscopic procedure is now being done in some centers, and may be associated with lower complication rates and shorter hospital stays

        1. Indications and Contraindications
          • excellent palliative procedure
          • many surgeons use this operation for ‘curative’ resections
          • contraindications include tracheobronchial invasion and fixation to surrounding structures
          • lowest mortality and major morbidity rates of all the esophageal resections

        2. Preoperative Considerations
          • if the stomach is not available as an esophageal replacement because of previous gastric surgery, then a barium enema of the colon is necessary to assess the suitability of the colon as the replacement organ

        3. Operative Considerations
          • must preserve the right gastroepiploic vessels
          • preserve the spleen
          • pyloromyotomy and feeding jejunostomy are routine
          • in the neck, the recurrent laryngeal nerves must be protected
          • must assess the mobility of the tumor before proceeding with the thoracic phase of the procedure
          • much of the ‘blunt’, ‘blind’ thoracic phase of the procedure may be done sharply and under direct vision by inserting long, narrow retractors through the esophageal hiatus
          • mediastinal dissection must be kept close to the esophageal wall
          • as the stomach is brought up into the neck, care must be taken not to twist the stomach in the posterior mediastinum

        4. Complications
          • intraoperative complications include pneumothorax, hemorrhage, and a tracheal tear
          • postoperative complications include hoarseness, anastomotic leak or stricture, chylothorax, and pleural effusion

      2. En Bloc Esophagogastrectomy
        • requires 3 incisions: right posterolateral thoracotomy, upper midline abdominal incision, left cervical incision
        • gastrointestinal continuity is usually restored with the stomach
        • radical thoracic and abdominal lymphadenectomies are performed
        • some studies claim significantly better survival rates for early cancers than with transhiatal esophagectomy
        • has the highest mortality and morbidity rate of all the esophageal resections
        • entire esophagus is resected, thereby eradicating submucosal spread
        • avoids an intrathoracic anastomosis

      3. Left Thoracoabdominal Approach
        • used for lesions in the distal esophagus and cardia
        • distal esophagus, proximal stomach, and adjacent lymph node basins are resected
        • a pyloroplasty or pyloromyotomy is required for gastric drainage
        • an intrathoracic anastomotic leak is the most feared and lethal complication
        • intrathoracic anastomoses are invariably associated with reflux
        • obtaining negative margins is difficult since esophageal carcinoma spreads extensively in the submucosal plane
        • there are increased respiratory complications from a combined thoracic and abdominal operation

      4. Ivor-Lewis Esophagogastrectomy
        • combines right thoracotomy and abdominal incisions
        • used primarily for lesions in the middle third of the esophagus
        • has all the drawbacks of a transthoracic esophagectomy
        • leak rates are low, but since they occur in the chest, they can be difficult to control
        • often done now with a minimally invasive approach (thoracoscopic/laparoscopic)

      5. Vagal-Sparing Esophagectomy
        • similar to THE
        • vagal nerves are preserved by stripping the esophagus away from the nerves
        • highly selective vagotomy is performed, so a pyloroplasty is not necessary
        • advocated for use in intramucosal tumors

    4. Palliative Therapy
      • ~50% of patients with esophageal carcinoma have local tumor invasion or distant metastases, precluding cure
      • primary goal is relief of dysphagia by reestablishing an esophageal lumen
      • combination chemotherapy and radiation does not improve survival but can improve local control
      • photodynamic therapy, endoscopic laser therapy, and esophageal stenting can all play roles in palliating dysphagia

Benign Esophageal Tumors

  1. Leiomyomas
    • now classified as GIST tumors (c-KIT-positive); true leiomyomas are rare
    • dysphagia and pain are the most common symptoms
    • have a distinctive appearance on barium swallow: smooth, concave defect with intact mucosa and sharp borders
    • esophagoscopy should be done to rule out carcinoma, but if a leiomyoma is suspected it should not be biopsied (scarring at the biopsy site complicates the extramucosal resection of the mass)
    • asymptomatic incidentally found small tumors may be safely followed with periodic barium swallows
    • symptomatic or large tumors should be removed by enucleation

    Gist Tumor of the Esophagus






References

  1. Sabiston, 19th ed., pgs 1047 – 1065
  2. Cameron, 11th ed., pgs 47 – 54, 54 – 58
  3. UpToDate. Barrett’s Esophagus: Surveillance and Management. Spechler MD, Stuart. Oct 15, 2018. Pgs 1 – 25
  4. UpToDate. Clinical Manifestations, diagnosis, and Staging of Esophageal Cancers. Saltzman MD, John, Gibson MD, Michael. Oct 22, 2018. Pgs 1 – 38
  5. UpToDate. Surgical Management of Resectable Esophageal and Esophagogastric Junction Cancers. Swanson MD, Scott. Feb 07, 2019. Pgs 1 – 51