Carcinoma of esophagus is the sixth most common cancer in the world. Carcinoma of esophagus is notorious in the sense that it spreads very early and only 25% of the patients are diagnosed at a stage where cure can be achieved. An estimated 80% of primary esophageal neoplasms are malignant. Squamous cell carcinoma and adenocarcinoma are the most common histologic subtypes of esophageal cancer. Both histologic subtypes have very different biological and epidemiologic profiles; consequently, esophageal squamous cell carcinoma and esophageal adenocarcinoma should be viewed as separate disease entities. Squamous cell carcinoma primarily occurs in the middle third of the esophagus, while
adenocarcinoma predominantly occurs in the lower third of the esophagus. Squamous cell carcinoma remains the most common histologic subtype of esophageal cancer worldwide.
Causes: causative factors are different for adenocarcinoma and squamous cell carcinoma
Adenocarcinoma: (lower 1/3rd)
Barrett's esophagus.
GERD
Obesity
High fat intake
High alcohol intake
Smoking
Squamous cell carcinoma: Middle 1/3rd
Smoking
Alcohol
Nitrosamine diet
Vitamin 'A ,C zinc and molybdenum' deficiency
Stricture
Long standing achalasia
Celiac disease
Tylosis: an autosomal dominant disorder characterized by hyperkeratosis of palmsand soles
Human papillomavirus
Presentations:
Dysphagia is the most common presenting symptoms
Retrosternal discomfort
Extension of tumor into tracheobronchial tree :stridor, coughing, choking and aspiration pneumonia
Hoarseness of voice: it may be due to paralysis of left recurrent laryngeal nerve or by direct invasion of tumor into the vocal cords:
Weight loss and anemia
Cervical lymphadenopathy
Investigations:
Endoscopy:
It is the first line investigation, providing direct visualization of the tumor and histology specimen for accurate diagnosis. Once the diagnosis is established the other investigations are only performed for accurate staging of the disease, these include
CT scan chest, abdomen and pelvis
Endoscopic ultrasonography (EUS)
Positron emission tomography (PET) in selected cases for liver Metastasis)
Bronchoscopy and laparoscopy
CT scan chest, abdomen and pelvis:
It provides useful information about the local extent of the tumor, invasion into the surrounding structures, mediastinal and abdominal lymph nodes involvement. It can also demonstrate disseminated disease (lungs, liver, peritoneum which are most common sites of involvement) if present.
Endoscopic Ultrasound (EUS):
In this technique a mini ultrasound probe is attached to the tip of the endoscope. By this method, the depth of wall penetration by the tumor (T1-T4) and presence of lymph nodes metastasis (NO or N1) can be determined with 80% accuracy. Curative resection should not be encouraged if tumor has invaded the adjacent structures (T4) and or more than 5 lymph nodes are involved
Bronchoscopy:
Upper one third and middle one third of the tumor are mostly advanced at the time of diagnosis. Bronchoscopy may reveal impingement or invasion of the main airway which is a sign of unresectability
Laparoscopy:
It is a useful technique to detect peritoneal disease.
Positron Emission Tomography:
PET relies on the high metabolic activity of the cancerous cells as compared to the normal cells. The patient is given a small dose of radiopharmaceutical agent 18F fluorodeoxyglucose (FDG). This enters the cells and is phosphorylated. FDG-6 phosphate cannot be metabolized further and being a high polar molecule cannot diffuse back out of the cell.
It emits gamma rays which are picked up by the gamma camera (hot spots) and thus tumor (metastatic) is identified. This technique is very useful to identify liver metastasis.
Staging:
The TNM Staging System for Esophageal Cancer:
PRIMARY TUMOR (T)
T1: Tumor invades lamina propria, muscularis mucosae, or submucosa
Tla: Tumor invades lamina propria or muscularis mucosae.
Tib: Tumor invades submucosa.
T2: Tumor invades muscularis propria.
T3:Tumor invades adventitia.
T4:Tumor invades adjacent structures.
REGIONAL LYMPH NODES (N)
NO: No regional lymph node metastasis.
N1: Regional lymph node metastasis.
DISTANT METASTASIS:
MO: No distant metastasis
M1: Distant metastasis.
Principles of treatment:
High grade dysplasia or subcentimeter nodule:
Endoscopic mucosal resection (EMR)
T1a, No = esophagectomy.
T1b, NO, T2 NO= esophagectomy + Local lymphadenectomy.
T3, NX = Esophagectomy + Lymphadenectomy,+ chemo and radiotherapy.
T4=Palliative treatment.
Stenting
Laser
Ethanol injection
Chemotherapy
Radiotherapy
It should be remembered that more than two third of the patients with esophageal cancer present to the hospital when the disease has crossed the limit of curative treatment, so most of
our treatment is palliative one. When the disease is confined to the esophagus T1-T3, there is no hematogenous spread and the patient is fit enough To undergo major surgery, the surgery is the best modality of treatment in adenocarcinoma as well as squamous aii carcinoma.
The tumors of the proximal third of esophagus the laryngopharyngectomy is also needed in are very difficult to be treated by surgery because these tumors get tumor free area and this extensive procedure carries high mortality and morbidity.
The patients who are unfit for surgery should be treated by chemo radiotherapy. Squamous cell
Carcinoma is considered to be radiosensitive tumors.
Contra-indications to surgery:
Systemic metastasis.
Involvement of vessels e.g. aorta.
Cervical lymphadenopathy.
Patients unfit for surgery due to severe cardio-pulmonary insufficiency
Esophagectomy should not be performed when RO resection is not possible
What is RO, R1 and R2 resection?
RO Resection:
Complete resection with no microscopic residual tumor (margins are microscopically negative according to the pathologist).
R1 Resection:
Complete resection with no grossly visible tumor as defined by the surgeon, but microscopic cancer may be left behind (margins are microscopically positive according to the pathologist
R2 Resection:
Partial resection, with grossly visible tumor left behind
Esophagectomy:
Esophagectomy is a major surgical intervention and should be performed after thorough assessment of the tumor (staging) and condition of the patient. 5cm of tumor free margin should be achieved on either side while doing esophagectomy
Esophagectomy can be performed by various methods which are given as.
Minimal invasive esophagectomy
Transhiatal esophagectomy
Ivor Lewis/Lewis-Tanner or two phase operation (Most widely practice)
McKeown or three phase operation
Salvage esophagectomy
Ivor lewis Procedure:
This is a two staged procedure. First upper midline incision is given, stomach and lower end of esophagus is mobilized preserving the right gastroepiploic artery and vein, then a right thoracotomy is performed during which the esophagus is resected and stomach is brought into the thorax to be anastomosed with the remaining esophagus.
McKeown Three Stage esophagectomy:
This is the same as Ivor Lewis procedure plus a third an incision is made in the neck. The esophagus is resected and the mobilized stomach is pulled up into the neck and cervical anastomosis is made. Mediastinal and abdominal lymphadenectomy can be performed under direct vision in Ivor Lewis and McKeown procedure
Transhiatal Resection:
In this procedure the stomach and upper midline incision are mobilized, another incision is given in the neck and cervical esophagus is mobilized through it. The diaphragm is opened through abdominal incision and posterior mediastinum is entered. The lower esophagus and the tumor are mobilized under direct vision and upper esophagus is mobilized by blunt dissection. The stomach is brought into the neck and cervical anastomosis is carried out after resecting the tumor bearing area with adequate tumor free margins (5cm on each side). The advantage of this procedure is that operation can be performed without opening the thorax but adequate lymphadenectomy cannot be performed by this method
All these procedures can also be performed by minimally invasive techniques. Abdominal part of the operation is performed via laparoscopy while the thoracic part can be performed via vide assisted thoracoscopy
Complications of esophagectomy:
Esophagectomy carries a morbidity of 20-80% and mortality ranges from 0-22%.various
complications include
Pulmonary complications: these are the major cause of morbidity and mortality and includes:
Atelectasis
Pneumonia
ARDS
Empyema
Leakage of anastomosis. It is more serious complication and occur in 0-40% of cases
Injury to thoracic duct leading to chylothorax and chyloperitoneum
Injury to recurrent laryngeal nerve
Injury to aorta (to arch of aorta in case of left thoracotomy) leading to hemorrhage
Wound complications.
Cardiac complications:
Acute atrial fibrillation
Myocardial infarction
Heart failure
Diaphragmatic herniation
Radiotherapy:
Radiotherapy is a very effective treatment modality in squamous cell carcinoma but adenocarcinoma is thought to be radio resistant. Studies are available, where radiotherapy found to be curative for squamous cell carcinoma but recurrence of the disease was high after radiotherapy and main disadvantage of radical radiotherapy was development of fibrous structures in about half of treated patients. The main contraindication of radiotherapy includes tracheoesophageal fistula and large size tumor (9cm). Radiotherapy is also used in combination with surgery to prevent local recurrence of the disease. It is also used as palliative treatment in advanced carcinoma to relieve dysphagia
.
Chemotherapy:
Various chemotherapeutic agents are available but their role is limited. It is mainly used in
combination with radiotherapy and surgery.
Commonly used anticancer drugs for esophageal cancer are Cisplatin and 5FU
Prognosis:
In general esophageal cancer has poor prognosis as most of the patients present a late stage, overall 5year survival is 15% but largely depends upon the stage of the disease.5 year survival according to the stage of disease is given below
T1:80%
T2:50%
T3:20%
T4: 07%
M1:03%
Palliative treatment:
In more than two third of the patients the esophageal carcinoma is diagnosed at the time when the limit of cure has crossed so most of the treatment is palliative (to relieve the symptoms) than curative. The main aim of palliative treatment is to relieve dysphagia. Nowadays
surgery is not performed as a palliative procedure. Following options are used to relieve the dysphagia caused by advanced esophageal
Intubations:
The tube can be passed across tumors through which food particles could pass.
Various types of tubes include souttar, Celestin, Atkinson and Procter living stone. Now the technology of intubations has improved by the development of expandable stents.
These stents are passed in collapsed form under radiological and endoscopic control. After placement these stents are expanded up to the desired diameter.
Laser therapy:
Endoscopic lasers can be used to destroy the tumor and to unblock the stents which have been encroached by the tumor. Other endoscopic methods include bipolar diathermy argon beam plasma coagulation and alcohol injection.
Radiotherapy:
Radiotherapy can be used to relieve dysphagia and to relieve bony pain caused
by metastatic deposits in the bones.
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