Carcinoma Esophagus

The esophagus is a muscular tube also known as food pipe in general public transmits food material from mouth (base of pharynx) to the stomach. Carcinoma of esophagus is one of the deadliest malignancies of human body. The incidence of this malignancy is increasing in general population due to life style modification as well as changes in environment.

Carcinoma of esophagus is divided into two types -

1. Squamous cell carcinoma - Cancer that forms in tissues lining the esophagus. Mostly found in upper and middle 1/3rd of esophagus. Incidence increases with age with most common age group between 55-60 years with male preponderance.

2. Adenocarcinoma - cancer that begins in esophageal lining cell that secret mucus. Most commonly found in lower esophagus and at the meeting point of esophagus and stomach. Commonly presented in patients with age group 50 years or younger.

Risk factors for Esophageal malignancy -

1. Smoking and alcohol - smoking for a long duration and chronic alcohol consumption

2. Esophageal inner mucosal lining damage from physical agents -
  • long term ingestion of hot liquids
  • caustic ingestion (corrosive poisoning)
  • radiation induced damage
3. Carcinogens in food and water - nitrates, nitrite, nitrosamine,
smoked opiates, fungal toxins in pickled
4. Obesity - increased risk for adenocarcinoma of esophagus. Incidence of gastroesophageal reflux increased in obesity due to lax lower esophageal junction to stomach which leads to Barrett's esophagus. If condition is not reverted with time Barrett's esophagus turns into malignancy.
5. Chronic iron deficiency anemia in females leading to plummer Vinson Syndrome
6. Congenital hyperkeratosis of palms and sole
7. Helicobactor pylori infection
8. Achalasia Cardia - long standing
9. Dietary deficiencies of molybdenum, Zinc, Vitamin A

Symptoms of esophageal malignancy

1. Dysphagia - Dysphagia is the most common presentation. Patient may have difficulty in swallowing of solid food in early stage of disease and solid as well as
    liquid food in the late stage of disease.
2. Weight loss - recent onset and significant.
3. Coughing and choking during meal.
4. Change in voice - hoarseness.
5. Weakness and easy fatigability.
6. Pain behind sternum - occasional
7. Heart burn and reflux
8. Malena and sometimes haematemesis.

Diagnosis of esophageal malignancy

The patient is evaluated on the basis of history, symptoms and clinical signs. Along with routine blood test and X-ray some endoscopic and radiological investigations are done which include -

1. Barium sallow x- ray - thin barium is allowed to shallow and x-ray of esophagus taken. This shows the site and outline of tumor.

2. Endoscopy - the endoscope is passed through mouth to esophagus to see the inner lining of esophagus and tumor. If it shows any abnormal growth then a small piece of tissue from the growth is taken for confirmation of the diagnosis. These tissues are examined under a microscope for the presence of cancer.

3. Bronchoscopy - in cases of advanced tumor arising from upper of esophageal an endoscope is passed into trachea (wind pipe) to rule out local spread of the tumor to lungs

4. Endoscopic Ultrasound - for early tumor endoscopic ultrasound is passed in esophagus to find out local spread of tumor.

5. For tumor staging radiological investigation like computed tomography (CT) scans of chest and abdomen and positron emission tomography (PET) scan are performed to determine outer spread of esophageal tumor to surrounding vital organs and distant spread to other organs.

6. Thoracoscopy and Laparoscopy - By this methods detection rate of lymphnodal and distal spread of esophageal malignancy is high.

Staging of esophageal tumors

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body.

According to AJCC Cancer Staging Manual, Seventh Edition (2010) cancer growth and spread can be staged by TNM system

Tumor (T) - means how deep the tumor has grown into the wall of the esophagus

Node (N) - tumor spread to lymph nodes

Metastasis (M) - metastasis (distal spread) to other part of the body

Based on combined results of T, N and M staging of cancer determined.

Tumor (T) is classified into
TX: tumor cannot be evaluated
T0: cancer is not detected in the esophagus
Tis: this is also called carcinoma in situ that means very early cancer
T1: tumor spread to the lamina propria and submucosal layers of esophagus
T2: tumor spread to muscular is propria
T3: tumor spread to the adventitia, the outer layer of the esophagus
T4: tumor has spread to surrounding structures of the esophagus, including the aorta, pericardium, large blood vessel, trachea, diaphragm, and pleural lining of the lung

Node (N) : N stands for Lymph nodes. Lymph nodes close to esophagus is called regional lymph nodes and those located in other part of body are distant lymph nodes.
NX: lymph nodes cannot be evaluated
N0: cancer cells not detected in lymph nodes
N1: cancer cells has spread to 1-2 lymph nodes in the chest, near the tumor
N2: cancer cells has spread to 3-6 lymph nodes in the chest, near the tumor
N3: cancer cells has spread to 7 or more lymph nodes in the chest, near the tumor

Distant metastasis (M):
this indicates whether the cancer cells has spread to other parts of the body
MX: Metastasis cannot be evaluated
M0: cancer cells has not spread to other parts of the body
M1: cancer cells has spread to another part of the body

Grading of esophageal tumor

G1: well differentiated
G2: mildly differentiated
G3: poorly differentiated
G4: not differentiated

Esophageal Cancer stageing

There are separate staging systems for both squamous cell carcinoma and adenocarcinoma of esophagus.

Staging of squamous cell carcinoma of the esophagus

Stage 0: Tis, N0, M0

Stage IA: T1, N0, M0

Stage IB:
T1, N0, M0
T2 or T3, N0, M0

Stage IIA:
T2 or T3, N0, M0
T2 or T3, N0, M0

Stage IIB:
T2 or T3, N0, M0
T1 or T2, N1, M0

Stage IIIA:
T1 or T2, N2, M0
T3, N1, M0
T4a, N0, M0

Stage IIIB:
T3, N2, M0

Stage IIIC:
T4a, N1 or N2, M0
T4b, any N, M0
any T, N3, M0

Stage IV : any T, any N, M1

Staging of adenocarcinoma of the esophagus

Stage 0: Tis, N0, M0

Stage IA: T1, N0, M0

Stage IB:
T1, N0, M0
T2, N0, M0

Stage IIA:
T2, N0, M0

Stage IIB:
T3, N0, M0
T1 or T2, N1, M0

Stage IIIA:
T1 or T2, N2, M0
T3, N1, M0
T4a, N0, M0

Stage IIIB:
T3, N2, M0

Stage IIIC:
T4a, N1 or N2, M0
T4b, any N, M0
any T, N3, M0

Stage IV : any T, any N, M1

Treatment of Esophageal cancer

Patients with esophageal cancer are managed based on its staging. Overall general condition of the patients affects management.

Stage I -

Tis and T1aN0 stage -
Endoscopic therapy like mucosal resection or submucosal dissection with the help of endoscopic ultrasound (EUS),

Photodynamic therapy,
Radiofrequency ablation
T1b N0 & T2 N0 stage - Surgery (esophagectomy) to remove the part of esophagus that contains the cancer

Stages II-III -
Chemoradiation followed by surgery (trimodal therapy)
Patient with squamous cell carcinoma with well preserved general condition chemotherapy and radiotherapy started before definitive surgery.
Patients with adenocarcinoma of lower end esophagus where stomach meet (gastroesophageal junction) are only chemotherapy is given before surgery. For smaller tumor (< 2 cm) only surgery is advised.
Patients with serious co-morbidities who are not candidate for surgery are managed with chemoradiation.

Stage IV -
Chemotherapy/ Radiotherapy or symptomatic and supportive care Treatment is given only for palliation to relieve the symptoms like pain, difficulties in swallowing etc.

Esophageal stenting (plastic/metallic) is done in situations where the patient is totally dysphagic and having esophagobroncheal fistula.
Patient who are unable to tolerate oral feeds a nasogastric tube may be required to continue feeding.
Some times gastrostomy/jejunostomy tube is required where patients become intolerant to nasogastric tube or tend to aspirate food.
Laser therapy is done in cases in which esophagus is totally occluded by cancer and the cancer cannot be removed by surgery. The relief of a blockage by laser can help to reduce dysphagia and pain

Chemotherapy may be given after surgery (adjuvant) to reduce risk of recurrence or before surgery (neoadjuvant) to down stage the disease.
Chemotherapy is cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks.
Recently epirubicin regimens is used in advanced nonresectable cancer.
Patients with adenocarcinoma with HER2 positive treated with targeted targeted therapy like trastuzumab.

Radiotherapy :

Radiotherapy is given before, during or after chemotherapy or surgery. It is also used in palliation to control pain.

Surgery is contraindications in following situation :
1. Locally advanced cancer engulfing adjacent vital structures like trachea, lung, pericardium, aorta recurrent laryngeal nerve
2. Esophageal Cancer with wide dissemination ( metastasis) to distant lymph nodes and vital organs
3. Severe co-morbidity involving cardiovascular and respiratory system

Surgical options :
Surgery is performed by either open or minimal invasive method depending upon patient's general condition and availability of experts. Now a days minimal invasive approach of esophagectomy has become very popular among surgeons because of low surgical morbidity, short hospital stay and similar onchological outcomes.

Types of esophagectomy-

1. Transhiatal esophagectomy (THE)
2. Transthoracic esophagectomy (TTE) - thoraco abdominal Mc Keown's & Ivor Lewis esophagectomy

In thoracoabdominal approach - both the abdominal and thoracic cavities opened together.

Ivor Lewis esophagectomy - two-stage approach involves an initial laparotomy and construction of a gastric tube, followed by a right thoracotomy to excise the tumor and create an esophagogastric anastomosis

McKeown esophagectomy - three-stage approach which include incision in the neck to complete the cervical anastomosis