Esophageal cancer

Esophageal cancer (or oesophageal cancer) is malignancy of the esophagus. There are various subtypes,
primarily adenocarcinoma (approx. 50-80% of all Esophageal cancer) and squamous cell cancer. Squamous cell
cancer arises from the cells that line the upper part of the esophagus. Adenocarcinoma arises from glandular cells
that are present at the junction of the esophagus and stomach.[1] Esophageal tumors usually lead to dysphagia
(difficulty swallowing), pain and other symptoms, and are diagnosed with biopsy. Small and localized tumors are
treated surgically with curative intent. Larger tumors tend not to be operable and hence are treated with palliative
care; their growth can still be delayed with chemotherapy, radiotherapy or a combination of the two. In some cases
chemo- and radiotherapy can render these larger tumors operable. Prognosis depends on the extent of the disease
and other medical problems, but is fairly poor.

Classification
Esophageal cancers are typically carcinomas which arise from the epithelium, or surface lining, of the esophagus.
Most esophageal cancers fall into one of two classes: squamous cell carcinomas, which are similar to head and neck
cancer in their appearance and association with tobacco and alcohol consumption, and adenocarcinomas, which are
often associated with a history of gastroesophageal reflux disease and Barrett's esophagus. A general rule of thumb
is that a cancer in the upper two-thirds is a squamous cell carcinoma and one in the lower one-third is a
adenocarcinoma.

Signs and symptoms

Dysphagia (difficulty swallowing) and odynophagia (painful swallowing) are the most common symptoms of
esophageal cancer. Dysphagia is the first symptom in most patients. Odynophagia may also be present. Fluids and
soft foods are usually tolerated, while hard or bulky substances (such as bread or meat) cause much more difficulty.
Substantial weight loss is characteristic as a result of poor nutrition and the active cancer. Pain, often of a burning
nature, may be severe and worsened by swallowing, and can be spasmodic in character. An early sign may be an
unusually husky or raspy voice.

The presence of the tumor may disrupt normal peristalsis (the organized swallowing reflex), leading to nausea and
vomiting, regurgitation of food, coughing and an increased risk of aspiration pneumonia. The tumor surface may be
fragile and bleed, causing hematemesis (vomiting up blood). Compression of local structures occurs in advanced
disease, leading to such problems as upper airway obstruction and superior vena cava syndrome. Fistulas may
develop between the esophagus and the trachea, increasing the pneumonia risk; this condition is usually heralded by
cough, fever or aspiration.

Most of the people diagnose with esophageal cancer have late-stage disease. This is because people usually don't
have significant symptoms until half of the inside of the esophagus, called the lumen, is obstructed, by which point the
tumor is fairly large.
If the disease has spread elsewhere, this may lead to symptoms related to this: liver metastasis could cause
jaundice and ascites, lung metastasis could cause shortness of breath, pleural effusions, etc. Causes

Increased risk

Barrett's esophagus is considered to be a risk factor for esophageal adenocarcinoma.

There are a number of risk factors for esophageal cancer.Some subtypes of cancer are linked to particular risk
factors:

 Age. Most patients are over 60, and the median in US patients is 67.
 Sex. It is more common in men.
 Heredity. It is more likely in people who have close relatives with cancer.
 Tobacco smoking and heavy alcohol use increase the risk, and together appear to increase the risk more
than either individually.
 Gastroesophageal reflux disease (GERD) and its resultant Barrett's esophagus increase esophageal cancer
risk due to the chronic irritation of the mucosal lining (adenocarcinoma is more common in this condition,
while all other risk factors predispose more for squamous cell carcinoma).
 Human papillomavirus (HPV)
 Corrosive injury to esophagus by swallowing strong alkalines (lye) or acids.
 Particular dietary substances, such as nitrosamine.
 A medical history of other head and neck cancers increases the chance of developing a second cancer in
the head and neck area, including esophageal cancer.
 Plummer-Vinson syndrome (anemia and esophageal webbing)
 Tylosis and Howel-Evans syndrome (hereditary thickening of the skin of the palms and soles).
 Radiation therapy for other conditions in the mediastinum.
 Coeliac disease predisposes towards squamous cell carcinoma.
 Obesity increases the risk of adenocarcinoma fourfold. It is suspected that increased risk of reflux may be
behind this association.
 Thermal injury as a result of drinking hot beverages
 Alcohol consumption in individuals predisposed to alcohol flush reaction
 Achalasia

Decreased risk

 Risk appears to be less in patients using aspirin or related drugs (NSAIDs).[13]

  The role of Helicobacter pylori in progression to esophageal adenocarcinoma is still uncertain, but, on the
basis of population data, it may carry a protective effect. [14][15] It is postulated that H. pylori prevents chronic
gastritis, which is a risk factor for reflux, which in turn is a risk factor for esophageal adenocarcinoma.
 According to the National Cancer Institute, "diets high in cruciferous (cabbage, broccoli, cauliflower) and
green and yellow vegetables and fruits are associated with a decreased risk of esophageal cancer."
 Moderate coffee consumption is associated with a decreased risk.
 According to one Italian study of "diet surveys completed by 5,500 Italians"—a study which has raised
debates questioning its claims among cancer researchers cited in news reports about it—eating pizza more
than once a week appears "to be a favorable indicator of risk for digestive tract neoplasms in this
population."

[edit] Diagnosis

Endoscopy and radial endoscopic ultrasound images of submucosal tumor in mid-esophagus.

Clinical evaluation

Although an occlusive tumor may be suspected on a barium swallow or barium meal, the diagnosis is best made with
esophagogastroduodenoscopy (EGD, endoscopy); this involves the passing of a flexible tube down the esophagus
and visualizing the wall. Biopsies taken of suspicious lesions are then examined histologically for signs of
malignancy.

Additional testing is usually performed to estimate the tumor stage. Computed tomography (CT) of the chest,
abdomen and pelvis, can evaluate whether the cancer has spread to adjacent tissues or distant organs (especially
liver and lymph nodes). The sensitivity of CT scan is limited by its ability to detect masses (e.g. enlarged lymph nodes
or involved organs) generally larger than 1 cm. FDG-PET (positron emission tomography) scan is also being used to
estimate whether enlarged masses are metabolically active, indicating faster-growing cells that might be expected in
cancer. Esophageal endoscopic ultrasound (EUS) can provide staging information regarding the level of tumor
invasion, and possible spread to regional lymph nodes.

The location of the tumor is generally measured by the distance from the teeth. The esophagus (25 cm or 10 inches
long) is commonly divided into three parts for purposes of determining the location. Adenocarcinomas tend to occur
distally and squamous cell carcinomas proximally, but the converse may also be the case.

Histopathology

Most tumors of the esophagus are malignant, only about 0.5% are benign. A very small proportion (under 10%) is
leiomyoma (smooth muscle tumor) or gastrointestinal stromal tumor (GIST). Malignant tumors are generally
adenocarcinomas, squamous cell carcinomas, and occasionally small-cell carcinomas. The latter share many
properties with small-cell lung cancer, and are relatively sensitive to chemotherapy compared to the other types.

Management

Self-expandable metallic stents are used for the palliation of esophageal cancer.

General approaches

Esophageal cancer affecting the lower esophageus. Insets show the tumor in more detail both before and after
placement of a stent.
The treatment is determined by the cellular type of cancer (adenocarcinoma or squamous cell carcinoma vs other
types), the stage of the disease, the general condition of the patient and other diseases present. On the whole,
adequate nutrition needs to be assured, and adequate dental care is vital.

If the patient cannot swallow at all, a stent may be inserted to keep the esophagus patent; stents may also assist in
occluding fistulas. A nasogastric tube may be necessary to continue feeding while treatment for the tumor is given,
and some patients require a gastrostomy (feeding hole in the skin that gives direct access to the stomach). The latter
two are especially important if the patient tends to aspirate food or saliva into the airways, predisposing for aspiration
pneumonia.

Esophagectomy is the removal of a segment of the esophagus; as this shortens the length of the remaining
esophagus, some other segment of the digestive tract (typically the stomach or part of the Colon or jejunum]) is
pulled up to the chest cavity and interposed.[20] If the tumor is unresectable or the patient is not fit for surgery,
palliative esophageal stenting can allow the patient to tolerate soft diet.

Types of esophagectomy:

 Thoracoabdominal approach- which opens the abdominal and thoracic cavities together.
 Two stage Ivor Lewis (also called Lewis-Tanner) approach- with an initial laparotomy and construction of a
gastric tube, followed by a right thoracotomy to excise the tumor and create an esophagogastric
anastomosis.
 Three stage McKeown approach- where a third incision in the neck is made to complete the cervical
anastomosis.

Endoscopic Therapy for Localized Disease There is accumulating data that endoscopic therapy is a safe, less
invasive, and effective therapy for very early esophageal cancer. The candidates for endoscopic therapy are Stage 1
patients with tumors invading into the lamina propria (T1 mucosal) or submucosa (T1 submucosal) that do not have
regional or distant metastasis. Patients with carcinoma in-situ or high-grade dysplasia can also be treated with
endoscopic therapy. Submucosa cancers with increased risk of nodal metastases may not be as amenable to
curative therapy.

The two forms of endoscopic therapy that have been used for Stage 0 and I disease are endoscopic mucosal
resection (EMR) and mucosal ablation using photodynamic therapy, Nd-YAG laser, or argon plasma coagulation.

EMR Endoscopic Mucosal Resection has been advocated for early cancers (that is, those that are superficial and
confined to the mucosa only) and has been shown to be a less invasive, safe, and highly effective nonsurgical
therapy for early squamous cell esophageal cancer. Preliminary reports also suggest its safety and efficacy for early
adenocarcinoma arising in Barrett’s esophagus. The prognosis after treatment with endoscopic mucosal resection is
comparable to surgical resection. This technique can be attempted in patients, without evidence of nodal or distant
metastases, with differentiated tumors that are slightly raised and less than 2 cm in diameter, or in differentiated
tumors that are ulcerated and less than 1 cm in diameter. The most commonly employed modalities of endoscopic
mucosal resection include strip biopsy, double-snare polypectomy, resection with combined use of highly
concentrated saline and epinephrine, and resection using a cap.

The strip biopsy method for endoscopic mucosal resection of esophageal cancer is performed with a double-channel
endoscope equipped with grasping forceps and snare. After marking the lesion border with an electric coagulator,
saline is injected into the submucosa below the lesion to separate the lesion from the muscle layer and to force its
protrusion. The grasping forceps are passed through the snare loop. The mucosa surrounding the lesion is grasped,
lifted, and strangulated and resected by electrocautery. The endoscopic double-snare polypectomy method is
indicated for protruding lesions. Using a double-channel scope, the lesion is grasped and lifted by the first snare and
strangulated with the second snare for complete resection.

Endoscopic resection with injection of concentrated saline and epinephrine is carried out using a double-channel
scope. The lesion borders are marked with a coagulator. Highly concentrated saline and epinephrine are injected
(15–20 ml) into the submucosal layer to swell the area containing the lesion and elucidate the markings. The mucosa
outside the demarcated border is excised using a high-frequency scalpel to the depth of the submucosal layer. The
resected mucosa is lifted and grasped with forceps, trapping and strangulating the lesion with a snare, and then
resected by electrocautery.
A fourth method of endoscopic mucosal resection employs the use of a clear cap and prelooped snare inside the cap.
After insertion, the cap is placed on the lesion and the mucosa containing the lesion is drawn up inside the cap by
aspiration. The mucosa is caught by the snare and strangulated, and finally resected by electrocautery. This is called
the "band and snare" or "suck and cut" technique. The resected specimen is retrieved and submitted for microscopic
examination for determination of tumor invasion depth, resection margin, and possible vascular involvement. The
resulting "ulcer" heals within 3 weeks.

Although most lesions treated in the esophagus have been early squamous cell cancers, endoscopic snare resection
can also be used to debulk or completely treat polypoid dysplastic or malignant lesions in Barrett’s esophagus. In a
preliminary report from Germany, EMR was performed as primary treatment or adjunctive therapy following
photodynamic therapy for early adenocarcinomas in Barrett's esophagus. The "suck and cut" technique (with and
without prior saline injection) was used as well as the "band and cut" technique. Although all tumors were resected
without difficulty, 12.5% developed bleeding (which was managed successfully by endoscopic therapy). Eighty-one
percent of the lesions were completely resected. The other lesions were also treated with other endoscopic
techniques. While this report suggests it is feasible to completely resect local, circumscribed, early adenocarcinomas
arising in Barrett's esophagus, the relative safety and efficacy of EMR in conjunction with photodynamic therapy is
unknown.

The major complications of endoscopic mucosal resection include postoperative bleeding and perforation and
stricture formation. During the procedure, an injection of 100,000 times diluted epinephrine into the muscular wall,
along with high frequency coagulation or clipping can be applied to the bleeding point for hemostasis. It is important
to administer acid-reducing medications to prevent postoperative hemorrhage. Perforation may be prevented with
sufficient saline injection to raise the mucosa containing the lesion. The "non-lifting sign" and complaints of pain when
the snare strangulates the lesion are contrainidications of EMR. When perforation is recognized immediately after a
procedure, the perforation should be closed by clips. Surgery should be considered in cases of endoscopic closure
failure. The incidence of complication range from 0–50% and squamous cell recurrence rates range from 0–8%.

Laser therapy is the use of high-intensity light to destroy tumor cells; it affects only the treated area. This is typically
done if the cancer cannot be removed by surgery. The relief of a blockage can help to reduce dysphagia and pain.
Photodynamic therapy (PDT), a type of laser therapy, involves the use of drugs that are absorbed by cancer cells;
when exposed to a special light, the drugs become active and destroy the cancer cells.

Chemotherapy depends on the tumor type, but tends to be cisplatin-based (or carboplatin or oxaliplatin) every three
weeks with fluorouracil (5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin
(ECF) was better than other comparable regimens in advanced nonresectable cancer.Chemotherapy may be given
after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible; in
this case, cisplatin and 5-FU are used. Ongoing trials compare various combinations of chemotherapy; the phase II/III
REAL-2 trial – for example – compares four regimens containing epirubicin and either cisplatin or oxaliplatin and
either continuously infused fluorouracil or capecitabine.

Radiotherapy is given before, during or after chemotherapy or surgery, and sometimes on its own to control
symptoms. In patients with localised disease but contraindications to surgery, "radical radiotherapy" may be used with
curative intent.

Follow-up

Patients are followed up frequently after a treatment regimen has been completed. Frequently, other treatments are
necessary to improve symptoms and maximize nutrition.