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Tumours Of Esophagus

  1. Types
Esophageal Carcinoma
  1. Most common site of ca esophagus is middle 1/3 of esophagus (AIIMS Feb 97)
  2. The commonest site of Ca esophagus in India is Middle 1/3 (AIIMS Nov 03)
  3. Most common site of SCC esophagus is middle 1/3. (60%)
  4. Most common site of adenocarcinoma of esophagus lower 1/3.
  1. Risk Factors
    1. Cigarette smoking and Alcohol drinking are the two major etiological factors of esophageal carcinomas. Incidences of heavy smoking and heavy drinking combined, increases the risk from 25 to100 folds.
    2. Diets low in beta-carotene, vitamins A, C, B, magnesium, and zinc
    3. Reduced consumption of fruits, vegetables, fresh meat, fresh fish and dairy products
    4. High level exposure to asbestos, ionizing.
    5. Drinking exceptionally hot beverages (tea).
    6. Human papilloma virus (AIIMS May 09)
    7. Medical history of head & neck cancers increases the chance of developing second cancer.
    8. Obesity
  2. Predisposing Conditions:

Predisposes towards squamous cell carcinoma

  1. Tylosis (PGI Dec 02)                                                    
  2. Achalasia                                        
  3. Caustic Injury
  4. Esophageal Diverticula (AIIMS May 09)              
  5. Esophageal Webs                          
  6. Celiac disease.

Risk factor for adenocarcinoma.
Barrett's Esophagus (AIPG 02, 98, AIIMS June 2000, Nov 96)  


Barrett's Esophagus (BE)
  1. Introduction
    1. Barrett’s esophagus is a metaplastic change in the mucosa of the esophagus in responsed to chronic gastro esophageal reflex.
    2. Barrett’s esophagus was identified by the presence of columnar mucosa extended atleast 3 cm in lower esophagus. (AIPG 02, AIIMS June 93 / Feb 97)
    3. It is not recognized that specialized intestinal type epithelum found in Barrett’s mucosa is the only tissue predisposed to adenocarcinoma.(AIIMS Nov 06)
    4. Consequently the diagnosis of Barrett’s esophagus is presently made given any length of endoscopically identifiable columnar mucosa that proves on biopsy to show intestinal metaplasia.
    5. The hall mark intestinal metaplasia is the presence of intestinal goblet cell.
  2. Pathophysiology

  1. Course
    1. Seven percent of the population suffers from symptomatic gastroesophageal reflux disease and 2-15% of those patients with chronic reflux disease develop Barrett's esophagus.
    2. Adenocarcinoma occurs in patients with Barrett's esophagus 30-40 times greater than the rate of the general population. Between 59-86% of adenocarcinomas arise in Barrett's esophagus.
    3. Treatment of choice for BE is PPI with regular survilliance with endoscopy.
      1. Non-surgical eradication of Barrett's Esophagus: Laser ablation of the unwanted columnar intestinal metaplasia can be accomplished in 60-80 %.
      2. There is no evidence yet that any of these method is effective in eliminating cancer risk of BE
    4. Follow up of patient with Barrett’s Esophagus
      For metaplasia Routine endoscopy 12-24 month
      Mild – Mod, dysplasia – endoscopy every 6 – 12 month because no evidence suggest that either medical or surgical therapy shop progression.
      High grade dysplasia – endoscopy every 3 month with LI quadrant biopsy or esophagectomy
    5. Barretts Esophagus : Grade of Dysplasia and proposed Follow. UP

ACA, adenocarcinoma; HGD, high-grade dysplasia; LGD, low-grade dysplasia.

CA Esophagus
Squamous Cell Carcinoma (Epidermoid Carcinoma)
  1. Squamous cell carcinoma has been the most common cell-type of esophageal cancers. However, in the last decade, the incidence of adenocarcinoma has increased an approximate 10% per year.
  2. It is no longer the leading form of esophageal cancer.
  3. Most common site middle 1/3 of esophagus.
  4. Afro-Americans are five times more likely to develop squamous cell carcinoma. Males are 4 to 6 times more  likely than females.
  5. Tumors of epidermoid carcinoma are located mainly in the thoracic esophagus. Approximately 60% are found in the middle third and about 30% in the distal third.
  6. Neoplasms can be of four major types:
    1. Fungating-type: Predominantly intraluminal growth with surface ulceration and extreme friability. This type frequently invades mediastinal structures.
    2. Ulcerating-type: Characterized by a flat based ulcer with slightly raised edges; hemorragic and friable and surrounding induration and erythema.
    3. Infiltrating-type: A dense firm logitudinal and circumferential intramural growth pattern.
    4. Polypoid: Intraluminal polypoid growth with a smooth surface on a narrow stalk. A five year survival of 70% is associated with the polypoid tumor compared to less than 15% five year survival for other types15
Esophageal adenocarcinoma now accounts for nearly 70% of all esophageal carcinomas diagnosed in the United States and Western countries. There are a number of factors that are responsible for this shift in cell type: 
1.    Increasing incidence of GERD
2.    Western diet
3.    Increased use of acid-suppression medications

Intake of caffeine, fats, and acidic and spicy foods all lead to decreased tone in the LES and an increase in reflux. As an adaptive measure, the squamous-lined distal esophagus changes to become lined with metaplastic columnar epithelium (Barrett's esophagus). Progressive changes from metaplastic (Barrett's esophagus) to dysplastic cells may lead to the development of esophageal adenocarcinoma. Histologically, esophageal adenocarcinoma arises from one of three places: 
1.    Submucosal glands of the esophagus
2.    Heterotopic islands of columnar epithelium
3.    Malignant degeneration of metaplastic columnar epithelium (Barrett's esophagus)

The male-to-female ratio for squamous cell cancer is 3:1; in contrast, the ratio for adenocarcinoma is 15:1 in the fifth decade of life. Squamous cell cancer is seen rarely before the age of 30 years, with the highest mortality rates seen among men between ages 60 and 70 years. Adenocarcinoma is seen infrequently before the age of 40 years and increases in incidence with age.
  1. Adenocarcinoma has been the second most common cell type of esophageal cancer, but now is the leading cell type of this type of cancer.
  2. Adenocarcinoma, by definition, is a carcinoma derived from glandular tissue or in which the tumor cells form recognizable glandular structures.
  3. This gland-like or gland-derived carcinoma arises from three sources: superficial and deep glands of the esophagus such as mucous glands, embryonic remnants of glandular epithelium, or metaplastic glandular epithelium.
  4. It is a cancer limited mainly to the lower third of the esophagus and arises mainly from the premalignant  condition, Barrett's esophagus. Patients presenting with adenocarcinoma are usually white males.
  5. Histologically, adenocarcinoma has distinctive small or large gland patterns. The cell lining of the glands have variable cytoplasmic differentiation. Unlike the mucin-secreting cells of origin, adenocarcinoma cytologically has a reduced cytoplasmic-nuclear ratio.
  6. A loss of cellular polarity demonstrates variable atypia and nuclear size, enlarged nucleoli and increased   mitoses.
  7. Pathology/Site
    1. Upper 1/3 - 15%
    2. Middle 1/3-40% (M.C. site for squamous cell cancer)
    3. Lower 1/3 - 45% (overall M.C. site for esophageal cancer).Adenocarcinomas now account for >50% of esophageal cancers. Incidence of squamous cell cancer has decreased in both the black and white population in the U.S., whereas the incidence of adenocarcinoma has risen dramatically)
  • Symptoms of Esophageal Carcinoma
  1. The most common symptoms are dysphagia (more to solid) and weight loss.
  2. Because of the elasticity of the esophagus, two-thirds of the lumen must be obstructed to produce dysphagia. Pain can be a symptom of this disease.
  3. It can come from the growth of the tumor, be related to swallowing, or be related to metastases into the surrounding esophageal lymph nodes.
  4. Less frequent symptoms are coughing or hoarseness. These are usually associated with tumors of the cervical esophagus.
  • Diagnosis
  1. Upper GI endoscopy and biopsy is the investigation of choice for CE esophagus.
  2. Chest radiograph:  The most common finding is an abnormal azygoesophageal recess.
  3. The next most frequent is widening of the mediastinum or posterior tracheal indentation.
  4. These findings may be seen on a CE CT is radiological investigation of choice.
  5. A barium swallow is performed to determine the extent of the tumor and its location.
  6. Barium swallow should be the first test performed on a patient whose symptom suggest esophageal cancer.
  7. Endoscopic ultrasound (EUS) is more senscitive and specific than CE CT for depth of lesion or T stage of tumor.
  8. The CT or EUS can determine the involvement of the mediastinal, perigastric, or celiac lymph nodes.
  9. The entire esophagus is visualized and tissue samples may be obtained for histological analysis. Biopsy and brush cytology may be performed.
  10. The accuracy of brush cytology alone is about 85-97% and biopsy alone ranging from 83-90%. The accuracy for the combination brush cytology and biopsy is 97-100%. 
  • Staging
  1. Techniques in radiology, such as barium esophogram, CT, and magnetic resonance imaging (MRI) are often used as a basis for clinical staging.
  2. EUS is the method of choice to determine depth of tumor invasion and regional nodal disease and involvement of adjacent structures.
  3. EUS is the most sensitive to determine depth of penetration & presence of enlarged periesophageal LN.
  4. Laparoscopy & thoracoscopy have greater then 92% accuracy in staging regional nodes.
Table: TNM Classification of Esophageal Carcinomas
T: Primary Tumor
TO No evidence of a primary tumor
Tis Carcinoma-in-situ (High-grade dysplasia)
T1 The tumor invades the lamina propria, muscularis mucosae, or submucosa but does not breach the boundary
between the submucosa and muscularis propria
T2 The tumor invades the muscularis propria but does not breach the boundary between the muscularis propria
and periesophageal tissue
T3 The tumor invades the periesophageal tissue but does not invade adjacent structures
T4 The tumor invades adjacent structures
N: Regional Lymph Nodes
NO No regional lymph node metastasis
N1  Regional lymph node metastasis
M: Distant Metastasis
MO No distant metástasis
M1  Distant metastasis
Tumor of the lower thoracic esophagus
M1a  Metastasis in celiac lymph nodes
M1b  Other distant metástasis
Tumor of the mid thoracic esophagus
M1a  Not applicable
M1b Nonregional lymph nodes and / or other distant metástasis
Tumors of the upper thoracic esophagus
M1a  Metastasis in cervical lymph nodes
M1b  Other distant metástasis

Table: Stage Grouping for Esophageal Cancer
Stage O:
Stage I:
Stage II:
T1 N1 MO
T2 N1 MO
Stage III:
T3 N1 MO
T4, any N, MO
Stage IV:
Any T, any N, M1
  • Treatment
  1. Treatment of choice for esophageal carcinoma is esophagectomy.
  2. 85 to 95% of patients have lymph node involvement at the time of surgical resection and with lymph node involvement, less than 10% survive five years.
  3. Palliation affords the patient the ability to swallow and perhaps resume a normal life.
  4. It has been found that the most used and useful approach is to use a combination of options.
  • Curative Treatment
  1. Surgery
    1. Only 50% of patients can undergo a curative resection.
    2. If a esophagectomy is indicated, there are three main types: A transhiatal esophagectomy without a thoracotomy, a "standard" (transthoracic) esophagectomy, or a en bloc esophagectomy are current methods.
    3. Regardless of technique, because of the unusual lymphatic system of the esophagus, malignant cells can be found a number of centimeters away (8-10 cm) from the primary lesion.
    4. Therefore, when the esophagectomy is performed, a generous margin is included and lymph node dissection is carried out.
  2. Transhiatal esophagectomy (THE)
    1. This surgical approach was fast described by Orringer for the management of Ca esophagus (J&K 05)
    2. Transhiatal esophagectomy is for adenocarcinoma lower end of esophagus. The approach would be in the order of abdomen à Neck. (AIIMS Nov 07) 
    3. The transhiatal esophagectomy with a cervical gastroesophageal anastomosis is the preference of some physicians.
    4. It is a highly debated technique because some believe it is not a preferred surgery because lymph node clearance is less and chances of vascular injury is more.
    5. THE carries a low operative mortality of 2-6% and a low anastomotic leak rate of 5-7.9%.
      1. Contraindications of performing any esophagectomy:-
      2. Evidence through endoscopy of invasion of the tracheobronchial tree, RLN, aorta, pericardium)
      3. Invasion of the diaphragmatic hiatus
      4. Evidence through a cervical incision of the tumor being fixed to nearby structures such as the pericardium, aorta, and/or tracheobronchial tree is a major contraindication to THE.
      5. Metastasis to M2 nodes (i.e., cervical or supraclavicular) or solid organs (Lungs or liver)
  3. Transthoracic esophagectomy
    1. The transthoracic esophagectomy is considered the "standard".
    2. Surgeons favor this approach over the THE because it allows a meticulous lymph node dissection, complete resection of tumor mass and adjacent tissue, and appropriate staging of the tumor which allows for a better chance of cure.
    3. Two of the main risks for this operation are a anastomotic leak and respiratory complications.
    4. Because of the relative location of the esophagus within the mediastinum, a left side thoracotomy is performed if the tumor in the distal third of the esophagus and a right side thoracotomy if it is in the middle and upper thirds.
  4. Ivor Lewis Esophagectomy:
    1. This procedure was proposed by Ivor Lewis in 1946.
    2. It consists of a laparotomy to mobilize the stomach as the conduit.
    3. Then, the esophagus is resected through a right posteriolateral thoracotomy incision and an intrathoracic esophagogastric anastomosis is performed.
    4. The Ivor Lewis esophagectomy is chosen for patients that have tumors of esophageal cancer of the  middle and lower third of the esophagus.
    5. Incidence of anastomotic leakage 6% in mediastinum but high mortality because of anastomotic leakage. 
  5. Total Thoracic Esophagectomy:
    1. This procedure also begins with a laparotomy as do all esophagectomies to mobilize the conduit of choice.
    2. The conduit, whether it be the stomach or the colon, is placed retrosternally and a cervical anastomosis is performed.
    3. A right thoracotomy is then made and the esophagus is resected.
    4. Incident of anatomotic leakage 12% but no mortality because of leakage.
  6. En Bloc Esophagectomy
    1. Because many patients present with metastases to regional lymph nodes as well as to the surrounding tissue and organs a more radical resection has been advocated; the en bloc esophagectomy.
    2. An envelope of normal tissue is removed along with the spleen, celiac nodes, posterior pericardium, azygous vein, thoracic duct, and adjacent diaphragm.
  7. Thorascopic Esophagectomy
    1. Because of their age or condition, some patients do not recover well from thoracotomy.
    2. The transhiatal approach is one alternative where thoracotomy is sparred, another newly developed approach is the thorascopic esophagectomy.
    3. This procedure is of interest because it is the only thoracotomy excluding technique that allows for a complete esophagectomy and a full lymphadenectomy.
  8. Reconstruction After Esophagectomy
    1. After a portion of the esophagus is removed or complete esophagectomy, a conduit must be established.
    2. The stomach, colon and jejunum have all been successfully used as an alternative channels, but the stomach appears to be the conduit of choice because of its ease in mobilization and tremendous vascular supply.
    3. The colon is used if the patient has undergone a partial or total gastrectomy previously or if metastases has spread to the stomach.
    4. Jejunal loops can also be used but their restricted mobility and possibly limited vascular supply limit the use of the jejunum as the conduit.
    5. Anastomosis can be performed in the chest just below the arch of the aorta (intrathoracic anastomosis), or the rest of the esophagus can be resected and a cervical anastomosis can be performed in the neck.
    6. Follow up:- On postoperative day 6, a swallow study is performed to check for anathematic leakage.
    7. Most common complication respiratory- atelectasis then closely followed by cardiac – arrhythmias.
    8. Squamous & adenocarcinoma have equivalent survival risk when matched stage by stage.
  • Radiation Therapy
  1. External Beam Radiation
    1. External beam radiation therapy may be used alone in the treatment of esophageal carcinoma but is not considered curative.
    2. For curative attempts, chemotherapy and/ or surgery generally accompanies this technique.
    3. Used alone, there is a 5-10% 5 year survival. Radiation therapy is contraindicated in the presence of a fistula or likely fistula formation.
    4. Radiation shrinks the tumor and often leads to fistula formation when the tumor has spread to the trachea or bronchus. 
    5. Make certain that local invasion has been adequately treated, the target includes a 5 cm margin on either side of the tumor.
    6. In addition to irradiating the tumor, lymph node stations are irradiated as well to treat possible metastatic disease.
    7. The supraclavicular and celiac lymph nodes are targets if the tumor is in either the upper or lower esophagus respectively.
    8. In the chest, the critical structures to avoid as much as possible are the lung, heart, spinal cord and bone marrow Limits of the entire lung are 1750 cGy or 4500 cGy for one third of the lung.
    9. The heart's tolerance is 4000 cGy and 6000 cGy for the entire and one third of the heart, respectively.
  2. Intracavitary Radiation (Intraluminal Brachytherapy)
    1. Intracavitary radiation is a technique that involves implanting a radiation source in or around the tumor.
    2. The radioactive source then delivers about 1000 cGy doses approximately 1-1.5 cm in diameter in or around the tumor.
    3. The tumor must therefore be quite small in order for this technique to work. It is used most often as a boost before or after external beam radiation therapy.
    4. Once external beam radiation therapy has shrunk the tumor to a desirable mass for intracavitary radiation, it is useful because it can deliver a cancercidal dose to cancerous cells without further radiating the spinal cord or lungs.
    5. Contraindications include stenosis, fistula, or deep ulceration. 
  • Chemotherapy
  1. It is used more commonly in conjunction with radiation and/or surgery.
  2. Chemotherapy is used preoperatively alone or combined with radiation to treat micrometastases and to reduce the size of the tumor in order to improve resectability rates.
  3. Also, if surgery is not an option, it is used with radiation to palliate and possibly improve survival.
  4. Chemotherapy is typically given in a combination of two or more chemotherapy drugs.
  5. The most prescribed drug is cisplatin. It has been most commonly combined with 5-fluorouracil (5-FU), vindesine, or bleomycin.
  6. Cisplatin and 5-FU is the most commonly prescribed combination in clinical trials. Cisplatin was used regularly in combination with bleomycin in the past; however, because of the pulmonary toxicity caused by bleomycin, trials have been discontinued.
  • Palliative treatment
  1. Palliation is appropriate when patients are too malnourished or debilitated to undergo surgery, have a tumor that is unresectable due to extensive invasion of vital structures, recurrence of resected or irradiated tumor, and/or due to metastases.
  2. Most of these patients have a complete or partial obstruction of the esophagus due to the tumor and swallowing is very painful or impossible.
  3. The goal of palliation is to use the least invasive means possible, limit hospitalization and relieve discomfort.
  4. Dependent upon the life expectancy, relief is carried out by surgery, radiotherapy with or without chemotherapy, intubation, dilation, photodynamic therapy, and/or laser therapy.
  • Surgery
  1. In most circumstances, esophageal cancer surgery is palliative by nature of its high probability of metastases at the time of surgical intervention.
  2. However surgery can be used as a means to relieve dysphagia while not attempting a curative resection. Two operations are performed; either an esophagectomy or a bypass. In either, instance, the risk of the procedure should be less than the anticipated 5 year survival rate.
  • Esophagectomy
  1. An esophagectomy is a surgical treatment in which the entire esophagus or a region of the esophagus is removed. As an alternative conduit, the stomach, colon or jejunum, may be used.
  2. This technique is preferable for low risk patients.
  • Bypass
  1. A palliative bypass may be useful (but not preferred) when a tumor is unresectable and severe dysphagia or tracheoesophageal fistula has occurred after radiochemotherapy.
  2. Tracheoesophageal fistula (TE) has a survival of weeks to months. Constant aspiration of food, liquids, and saliva cause an extremely unpleasant death.
  3. Bypass should be proposed for younger, healthier patients.
  • Stenting:
  1. Palliation of choice for dysphagia for Ca esophagus upper GI endoscopy and stenting.
  2. Palliation of choice for T-E fistula in Ca esophagus is stenting.
  3. The purpose of a stent is to bridge the obstruction in the esophagus with a rigid device that will allow for a re-establishment of luminal patency.
  4. The flexible self-expanding stent is made up of two layers of superalloy monofilament wire with a layer of silicon in between.
  5. The addition of the polymer in between the layers of mesh wire is a relatively new addition that extends the time the stent can be beneficial to the patient by preventing tumor overgrowth through the holes in the wire mesh.
  6. Patients are placed under local or general anesthesia and the stricture is dilated to 42-45F using a flexible gastroscope and Savary bougies.
  7. The lesion is marked and insertion of the stent is carried out under fluoroscopic control.
  8. The procedure is very often successful, >90% and patients can begin the routine of eating normal foods.
  9. Patients complain of chest pain in almost 100% of the cases because of the stretching of the stricture. Also hematemesis and nausea are possible complications. 
  • Recent Advances:
  1. EMR (Endoscopic Mucosal Resection)
    Indication : Stage a stage I disease (i.e. ulcerated lesion < 1cm early cancer that are superficial, sughly raised lesion <2cm confined to the mucosa only)
    Prognosis : After treatment with EPIR comparable to   surgical resection.
    Contraindication : Evidence of nodal or distant metastasis.
    Technique used : Strip biopsy / double snore polypectomy / resection with combined use of highly. Concentrated saline & epinephrine / suck & cut technique.
Management of Ca esophagus (Ref: Schwartz's Principles of Surgery 9th Edition Ch 25)

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