Esophageal Cancer

Aka: Esophageal Cancer, Esophageal Carcinoma, Squamous Cell Carcinoma of the Esophagus, Esophageal Adenocarcinoma

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II. Epidemiology

  1. Incidence in U.S. (2016): 16,910 diagnosed (15,910 deaths)
  2. Worldwide, 8th most common cancer
    1. 80% of cases occur in non-industrialized countries (esp. Asia, Africa)

III. Types

  1. Squamous Cell Carcinoma of the Esophagus
    1. Accounts for 90% of cases worldwide, but much less common in the U.S.
      1. Incidence: 3 per 100,000 person-years in U.S,
      2. Most common in China, Central Asia, East Africa, South Africa
    2. Typical: 60 to 70 year old black male
      1. Black patients predominate by 3 fold (compared with white patients)
    3. Conditions predisposing to cancer development
      1. Tobacco Smoking (RR 9)
      2. Alcohol Abuse (RR 2-3 if >=3 drinks/day)
      3. Diet low in vegetables and fruits (high starch diet)
      4. Achalasia (RR 10)
      5. Plummer-Vinson surgery
      6. Other head and neck surgery or radiation
  2. Adenocarcinoma of the Esophagus
    1. Most common cause in U.S.
    2. Incidence at age 65 years: 11.8 to 16.3 per 100,000 person-years (U.S.)
    3. Typical: 50 to 60 year old white male
      1. Males predominate by 8 fold
      2. White patients predominate by 5 fold (compared with black patients)
    4. Conditions predisposing to cancer development
      1. Tobacco Abuse (RR 2)
      2. Obesity (RR 2-4)
      3. Barrett's Esophagus
      4. Gastroesophageal Reflux (RR 5-7)
      5. Hiatal Hernia
      6. Scleroderma
      7. Zollinger-Ellison syndrome
      8. Achalasia history with status-post myotomy
  3. Other rare types (<5% of total cases)
    1. Lymphoma, Sarcoma, Melanoma and Carcinoid Tumors involving the Esophagus

IV. Symptoms

  1. Initial
    1. Asymptomatic
  2. Presentation (most common Esophageal Cancer presentations)
    1. Progressive symptoms on Swallowing for months
      1. Progressive solid Dysphagia to liquid Dysphagia
      2. Odynaphagia (painful Swallowing, esp with dry foods)
    2. Unintentional Weight Loss (10% over <3-6 months)
  3. Later
    1. Dyspepsia
    2. Heartburn
    3. Trunk pain
      1. Initially Swallowing-induced (constant later)
      2. Location of pain
        1. Chest and upper back: Upper 2/3 of Esophagus
        2. Abdomen and low back: Lower third of Esophagus
    4. Other symptoms or signs
      1. Halitosis
      2. Digital Clubbing
      3. Hematemesis or Hemoptysis

V. Signs: Suggesting local tumor spread

  1. Hoarseness (Recurrent laryngeal nerve involvment, 10% of patients)
  2. Horner Syndrome
  3. Cervical Lymphadenopathy
  4. Peristent Hiccups (diaphragm association)

VI. Diagnosis

  1. Upper Endoscopy with stains (chromoendoscopy), color filters, biopsies and brushings (see evaluation below)
  2. Endoscopic Ultrasound for invasive disease (see evaluation)
    1. Indicated if no distant metastases
    2. Identifies tumor depth and and nodal involvement
    3. May also guide fine needle biopsy
    4. Efficacy in identifying tumor invasion
      1. Test Sensitivity: 82-87%
      2. Test Specificity: 73-78%

VII. Labs

  1. Complete Blood Count (CBC)
    1. Anemia
  2. Liver Transaminases (AST, ALT)
    1. Increased with liver metastases
  3. Alkaline Phosphatase
    1. Increased with bone metastases
  4. Other labs per oncology
    1. HER2/neu overexpression
      1. Determine if Trastuzumab (Herceptin) candidate in those with metastatic esophageal junction cancer

VIII. Imaging: Evaluate Involvement and Differential Diagnosis

  1. CT Chest, Abdomen and Pelvis
    1. Performed with intravenous and Oral Contrast
    2. More sensitive than PET for evaluating local regional lesions
  2. Positron Emission Tomography (PET)
    1. Perform with CT if Esophageal Cancer is confirmed
    2. More sensitive than CT for identifying distant metastases
  3. Imaging Efficacy for identifying metastases (Integrated PET-CT)
    1. Test Sensitivity: 69-78%
    2. Test Specificity: 82-88%

IX. Evaluation

  1. Step 1: Upper endoscopy with stains (chromoendoscopy), color filters, biopsies and brushings
    1. If cancer present, go to step 2a
    2. Otherwise treatment based on findings
      1. Gastroesophageal Reflux
      2. Barrett's Esophagus
  2. Step 2a: Evaluate for metastases
    1. CT Chest, Abdomen and Pelvis with intravenous and Oral Contrast
    2. Positron Emission Tomography (PET) in combination with CT is preferred
    3. Labs (see above)
  3. Step 2b: Are distant metastases present?
    1. No distant metastases: Step 4a
    2. Distant Metastases
      1. Palliative measures (see management below)
  4. Step 3a: Obtain Endoscopic Ultrasound
    1. No Lymphovascular Invasion: Go to Step 4
    2. Lymphovascular Invasion
      1. Perform fine needle aspirate (FNA) of lesions during endoscopic Ultrasound
  5. Step 4: No Lymphovascular Invasion on Endoscopic Ultrasound
    1. Lesion <2 cm and limited to mucosa or lamina propria (Tis or T1a)
      1. Endoscopic mucosa resection
    2. Lesion >= 2 cm or submucosal invasion (T1b, T2, T3)
      1. Esophagectomy with Lymphadenectomy

X. Staging: AJCC Cancer Staging TNM

  1. Primary Tumor (T)
    1. Tis: High grade dysplasia
    2. T1a: Invades lamina propria
    3. T1b: Invades submucosa
    4. T2: Invades muscularis propria
    5. T3: Invades adventitia
    6. T4a: Invades nearby structures and is resectable (e.g. pleura, Pericardium, diaphragm)
    7. T4b: Invades nearby structures and is not resectable (e.g. aorta, Vertebrae, trachea)
  2. Regional Lymph Nodes (N)
    1. N0: No regional Lymph Node involvement
    2. N1: 1-2 positive regional Lymph Nodes
    3. N2: 3-6 positive regional Lymph Nodes
    4. N3: >6 positive regional Lymph Nodes
  3. Distant Metastases (M)
    1. M0: No distant metastases
    2. M1: Distant Metastases
  4. Stages
    1. Stage 0: Carcinoma in-situ
    2. Stage I: (T1-N0-M0)
      1. Tumor invades to lamina propria or submucosa
    3. Stage IIA: (T2-N0-M0) through (T3-N0-M0)
      1. Tumor invades to muscularis propria or adventitia
    4. Stage IIB: (T1-N1-M0) or (T1-N1-M0)
      1. Regional Lymph Node spread
    5. Stage III: (T3-N1-M0) or (T4-N1-M0)
      1. Local invasion to at least adventitia and
      2. Regional Lymph Node spread
    6. Stage IV (M1)
      1. Distant Metastases
  5. References
    1. Rice (2010) Ann Surg Oncol 17(7): 1721-4 [PubMed]

XI. Grading

  1. G1: Well differentiated
  2. G2: Moderately differentiated
  3. G3: Poorly differentiated
  4. G4: Undifferentiated

XII. Management

  1. Localized Esophageal Cancer (41% five year survival)
    1. Stage 0-Ia (Tis-T1b N0 M0)
      1. Localized involvement lamina or submucosa (but no deeper)
        1. Lymphatic spread risk <2%
      2. Management
        1. Endoscopic mucosal resection (complelety resected in 91-98%)
    2. Stage Ib-IIa: (T2-N0-M0) through (T3-N0-M0)
      1. Tumor invades deeper than the submucosa, but no known Lymph Node involvement
        1. Still asssociated with a 20% risk of Lymph Node involvement
      2. Management
        1. Laparoscopic esophagectomy with lymphadenectomy
  2. Regional Esophageal Cancer (23% five year survival)
    1. Stage IIB to IIIC (Tany, N1-3, M0)
    2. Management
      1. Esophagectomy with lymphadenectomy
        1. High Risk Surgery (30-50% major complication rate, 5% mortality)
      2. Perioperative Chemotherapy or chemoradiotherapy (esp. Stage III, squamous cell cancer)
  3. Metastatic Esophageal Cancer - Stage IV (5% five year survival, accounts for 75% of cases at time of diagnosis)
    1. Management: Palliative measures for Stage IV
      1. Brachytherapy
      2. Esophageal dilation or Esophageal bypass
      3. Jejunostomy tube or Gastrostomy Tube
      4. Palliative Chemotherapy (esp. squamous cell cancer)
      5. Mucosal stents (self-expanding)
      6. Laser fulguration
      7. Trastuzumab (Herceptin)

XIII. Prevention

  1. General
    1. No strong evidence as of 2016 for high efficacy of any prevention strategy
    2. No asymptomatic screening
  2. Tobacco Cessation
  3. Decrease Alcohol and Caffeine
  4. Increase vegetables and fruits in diet
  5. Manage Achalasia and strictures
  6. Control Gastroesophageal Reflux

XIV. Prognosis

  1. Five year survival: 15-20% (in U.S. and in World)
  2. Five year survival in U.S.
    1. Localized Esophageal Cancer: 41%
    2. Regional Esophageal Cancer: 23%
    3. Metastatic Esophageal Cancer: 5%

XV. References

  1. Layke (2006) Am Fam Physician 73(12):2187-94 [PubMed]
  2. Rustgi (2014) N Engl J Med 371(26): 2499-509 [PubMed]
  3. Short (2017) Am Fam Physician 95(1): 22-8 [PubMed]
  4. Wang (2004) Curr Opin Gastroenterol 20:381-5 [PubMed]

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Related Studies

Ontology: Esophageal carcinoma (C0152018)

Definition (NCI) A malignant epithelial tumor arising from the esophageal mucosa. Two major histologic types of esophageal carcinoma have been described: squamous cell carcinoma and adenocarcinoma. This type of cancer is associated with excessive ethanol and cigarette usage.
Definition (NCI_NCI-GLOSS) Cancer that forms in tissues lining the esophagus (the muscular tube through which food passes from the throat to the stomach). Two types of esophageal cancer are squamous cell carcinoma (cancer that begins in flat cells lining the esophagus) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids).
Concepts Neoplastic Process (T191)
SnomedCT 255079005, 154441003, 93785002, 372138000
English CARCINOMA OF ESOPHAGUS, ESOPHAGEAL CARCINOMA, CARCINOMA OF OESOPHAGUS, OESOPHAGEAL CARCINOMA, Carcinoma of esophagus NOS, ESOPHAGEAL CANCER, carcinoma of esophagus (diagnosis), carcinoma of esophagus, Esophageal carcinoma NOS, Oesophageal carcinoma NOS, Carcinoma of oesophagus NOS, esophageal carcinoma, Carcinoma;oesophagus, carcinoma esophagus, carcinoma of oesophagus, esophagus carcinoma, carcinoma esophageal, carcinoma oesophagus, oesophageal carcinoma, carcinoma esophageal cancer, Carcinoma of oesophagus (disorder), Cancer of oesophagus, Esophageal cancer, NOS, esophageal cancer, Oesophageal carcinoma, Carcinoma of esophagus, Carcinoma of oesophagus, Carcinoma of esophagus (disorder), Esophageal carcinoma, Esophageal Cancer, Cancer of Esophagus, Cancer of the Esophagus, Esophageal Carcinoma, Esophagus Carcinoma, Carcinoma of Esophagus, Carcinoma of the Esophagus, Carcinoma;esophagus, carcinoma of the esophagus, carcinoma of the oesophagus
Italian Carcinoma dell'esofago, Carcinoma dell'esofago NAS
Dutch slokdarmcarcinoom NAO, carcinoom van de slokdarm, carcinoom van de slokdarm NAO, slokdarmcarcinoom
French Cancer de l'oesophage SAI, Carcinome de l'oesophage, Carcinome oesophagien SAI, Carcinome de l'oesophage SAI, CANCER DE L'OESOPHAGE, CARCINOME DE L'OESOPHAGE, Carcinome oesophagien
German Karzinom der Speiseroehre NNB, Karzinom des Oesophagus NNB, oesophageales Karzinom, Karzinom des Oesophagus, oesophageales Karzinom NNB, KARZINOM OESOPHAGUS, OESOPHAGUSKARZINOM, Oesophaguskarzinom
Portuguese Carcinoma do esófago NE, Carcinoma do esófago, CARCINOMA DO ESOFAGO, CARCINOMA ESOFAGICO, Carcinoma esofágico
Spanish Carcinoma de esófago, Carcinoma de esófago NEOM, Carcinoma esofágico NEOM, CARCINOMA ESOFAGICO, ESOFAGO, CARCINOMA, carcinoma de esófago (trastorno), carcinoma de esófago, Carcinoma esofágico
Japanese 食道癌ＮＯＳ, 食道癌, ｼｮｸﾄﾞｳｶﾞﾝNOS, ｼｮｸﾄﾞｳｶﾞﾝ
Czech Karcinom jícnu, Karcinom jícnu NOS
Hungarian Oesophagus carcinomája, Nyelőcső eredetű carcinoma k.m.n., Oesophagealis carcinoma k.m.n., Nyelőcső carcinoma, Oesophagus k.m.n. carcinomája, Oesophagealis carcinoma, Nyelőcső eredetű carcinoma
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Squamous cell carcinoma of esophagus (C0279626)

Definition (NCI) A squamous cell carcinomas arising from the esophagus. It is associated with a long history of tobacco and alcohol abuse and is exceedingly rare before the age of 30. The median age is around 65 in both males and females. It is located mostly in the middle and lower third of the esophagus. Grossly, polypoid, ulcerated, plaque-like and occult lesions have been described. The microscopic features are the same as in other squamous cell carcinomas. Any degree of differentiation may occur, and variation within a single tumor is common. The prognosis is poor.
Concepts Neoplastic Process (T191)
MSH C562729
SnomedCT 276804009
English SCC-Squam cell carcinom oesoph, Squam cell carcinoma oesophag, Esophageal squamous cell carcinoma NOS, Squamous cell carcinoma of esophagus, squamous cell carcinoma of esophagus (diagnosis), squamous cell carcinoma of esophagus, Esophageal squamous cell carcinoma stage unspecified, Squamous cell carcinoma of esophagus NOS, Oesophageal squamous cell carcinoma NOS, Esophageal epidermoid carcinoma NOS, Oesophageal epidermoid carcinoma NOS, carcinoma cell esophagus squamous, ESCC, Esophageal Squamous Cell Carcinoma, Esophageal squamous cell carcinoma, Oesophageal squamous cell carcinoma stage unspecified, Squamous cell car. - esophagus, Squamous cell carcinoma of the esophagus, Oesophageal squamous cell carcinoma, SCC - Squamous cell carcinoma of esophagus, SCC - Squamous cell carcinoma of oesophagus, Squamous cell carcinoma of oesophagus, Squamous cell carcinoma of esophagus (disorder), squamous cell carcinoma of the esophagus, esophageal cancer, squamous cell, esophagus cancer, squamous cell, squamous cell esophageal cancer, squamous cell esophagus cancer, Esophageal Epidermoid Carcinoma, Esophageal SCC, Esophagus SCC, Esophagus Squamous Cell Carcinoma, SCC of Esophagus, SCC of the Esophagus, Squamous Cell Carcinoma of Esophagus, Squamous Cell Carcinoma of the Esophagus
Italian Carcinoma a cellule squamose dell'esofago, Carcinoma epidermoidale dell'esofago NAS, Carcinoma a cellule squamose dell'esofago NAS, Carcinoma a cellule squamose dell'esofago stadio non specificato, Carcinoma epidermoide dell'esofago NAS, Carcinoma spinocellulare dell'esofago NAS
Dutch slokdarmsquameuscelcarcinoom NAO, slokdarm epidermoïdcarcinoom NAO, squameuscelcarcinoom van slokdarm, oesofageaal squameuscelcarcinoom, squameuscelcarcinoom van de slokdarm, slokdarm squameuscelcarcinoom stadium niet-gespecificeerd, squameuscelcarcinoom van de slokdarm NAO, slokdarmsquameuscelcarcinoom
French Carcinome oesophagien épidermoïde stade non précisé, Cancer épidermoïde de l'oesophage SAI, Carcinome oesophagien épidermoïde SAI, Carcinome oesophagien épidermoïde, Carcinome épidermoïde de l'oesophage, Carcinome épidermoïde de l'oesophage SAI, Cancer épidermoïde de l'oesophage
German Epidermoidkarzinom der Speiseroehre NNB, Plattenepithelkarzinom der Speiseroehre Stadium unbekannt, Plattenepithelkarzinom der Speiseroehre NNB, Plattenepithelkarzinom der Speiseroehre
Portuguese Carcinoma pavimentocelular do esófago NE, Carcinoma epidermóide do esófago NE, Carcinoma pavimentocelular do esófago estádio NE, Carcinoma epidermóide esofágico NE, Carcinoma pavimentocelular do esófago
Spanish Carcinoma de células escamosas de esófago, Carcinoma esofágico epidermoide NEOM, Carcinoma esofágico de células escamosas, estadio no especificado, Carcinoma de células escamosas de esófago NEOM, Carcinoma de células escamosas del esófago, Carcinoma esofágico de células escamosas NEOM, Carcinoma de células escamosas esofágico, estadío no especificado, carcinoma de células escamosas del esófago (trastorno), carcinoma de células escamosas del esófago, carcinoma escamoso del esófago, Carcinoma esofágico de células escamosas
Japanese 食道扁平上皮癌ＮＯＳ, 食道扁平上皮癌, 食道扁平上皮癌、病期不明, ｼｮｸﾄﾞｳﾍﾝﾍﾟｲｼﾞｮｳﾋｶﾞﾝNOS, ｼｮｸﾄﾞｳﾍﾝﾍﾟｲｼﾞｮｳﾋｶﾞﾝﾋﾞｮｳｷﾌﾒｲ, ｼｮｸﾄﾞｳﾍﾝﾍﾟｲｼﾞｮｳﾋｶﾞﾝ, ｼｮｸﾄﾞｳﾙｲﾋｮｳﾋｶﾞﾝNOS, 食道類表皮癌ＮＯＳ
Czech Skvamózní karcinom jícnu NOS, Epidermoidní karcinom jícnu NOS, Dlaždicobuněčný karcinom jícnu stadium blíže neurčeno, Skvamózní karcinom jícnu, Dlaždicobuněčný karcinom jícnu NOS, Dlaždicobuněčný karcinom jícnu, Skvamózní karcinom jícnu stadium blíže neurčeno
Hungarian Nyelőcső squamosus-sejtes carcinoma, stádium nem meghatározott, Oesophagealis squamosus sejtes carcinoma, Nyelőcső squamosus-sejtes carcinomája, Oesophagealis squamosus-sejtes carcinoma, Oesophagealis squamosus-sejtes carcinoma, stádium nem meghatározott, Oesophagealis epidermoid carcinoma k.m.n., Nyelőcső squamosus-sejtes carcinomája k.m.n., Oesophagus squamosus-sejtes carcinomája, Nyelőcső eredetű epidermoid carcinoma k.m.n., Oesophagealis squamosus sejtes carcinoma k.m.n.
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Adenocarcinoma Of Esophagus (C0279628)

Definition (NCI) A malignant tumor with glandular differentiation arising predominantly from Barrett mucosa in the lower third of the esophagus. Rare examples of esophageal adenocarcinoma deriving from ectopic gastric mucosa in the upper esophagus have also been reported. Grossly, esophageal adenocarcinomas are similar to esophageal squamous cell carcinomas. Microscopically, adenocarcinomas arising in the setting of Barrett esophagus are typically papillary and/or tubular. The prognosis is poor.
Concepts Neoplastic Process (T191)
MSH C562730
SnomedCT 276803003
Italian Adenocarcinoma dell'esofago, Adenocarcinoma dell'esofago NAS
English Esophageal adenocarcinoma NOS, adenocarcinoma of esophagus (diagnosis), adenocarcinoma of esophagus, Esophageal adenocarcinoma, Oesophageal adenocarcinoma NOS, esophageal adenocarcinoma, adenocarcinoma esophagus, adenocarcinoma esophageal, cancer esophagus adenocarcinoma, adenocarcinoma oesophagus, esophagus adenocarcinoma, oesophageal adenocarcinoma, ADENOCARCINOMA OF ESOPHAGUS, Adenocarcinoma Of Esophagus, Adenocarcinoma - esophagus, Adenocarcinoma of the esophagus, Oesophageal adenocarcinoma, Adenocarcinoma of esophagus, Adenocarcinoma of oesophagus, Adenocarcinoma of esophagus (disorder), adenocarcinoma of the esophagus, esophageal cancer, adenocarcinoma, esophagus cancer, adenocarcinoma, Esophageal Adenocarcinoma, Esophagus Adenocarcinoma, Adenocarcinoma of Esophagus, Adenocarcinoma of the Esophagus, Oesophageal Adenocarcinoma NOS
Dutch slokdarmadenocarcinoom NAO, adenocarcinoom van de slokdarm, slokdarmadenocarcinoom
French Adénocarcinome de l'oesophage SAI, Adénocarcinome de l'oesophage, Adénocarcinome oesophagien
German Adenokarzinom des Oesophagus, oesophageales Adenokarzinom, Adenokarzinom der Speiseroehre NNB, Adenokarzinom der Speiseroehre
Portuguese Adenocarcinoma do esófago, Adenocarcinoma do esófago NE, Adenocarcinoma esofágico
Spanish Adenocarcinoma de esófago, Adenocarcinoma esofágico NEOM, adenocarcinoma de esófago (trastorno), adenocarcinoma de esófago, Adenocarcinoma esofágico
Japanese 食道腺癌ＮＯＳ, 食道腺癌, ｼｮｸﾄﾞｳｾﾝｶﾞﾝ, ｼｮｸﾄﾞｳｾﾝｶﾞﾝNOS
Czech Adenokarcinom jícnu, Adenokarcinom jícnu NOS, Ezofageální adenokarcinom
Hungarian Oesophagus adenocarcinoma, Nyelőcső adenocarcinoma, Oesophagealis adenocarcinoma k.m.n., Oesophagealis adenocarcinoma
Derived from the NIH UMLS (Unified Medical Language System)

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