Gastroenterology training and education

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Oesophageal carcinoma

The majority of oesophageal cancers are squamous cell (SCC) or adenocarcinoma (AC).

Adenocarcinoma	Squamous cell carcinoma
Incidence is rising dramatically	Incidence is falling
Largely a disease of male caucasians	Highest rates in blacks and Asians
Alcohol not an important risk factor. Smoking is a risk factor especially in Barrett’s oesophagus	Smoking and alcohol- major risk factors
Predisposing factors- Barrett’s, Chronic reflux, Obesity, absence of H.Pylori (?)	Achalasia, caustic strictures, Tylosis
Majority are located near GO junction	Midportion of the oesophagus

Clinical manifestations

• Dysphagia- usually occurs once the oesophageal lumen diameter is less than 13 mm.
• Weight loss
• Tracheobronchial fistulas-The fistulas are caused by direct invasion through the oesophageal wall and into the main stem bronchus. Life expectancy is less than four weeks following the development of this complication.

Investigations

• OGD and biopsies (at least 8 biopsy samples)- A classification of oesophagogastric tumours, proposed by Siewert and Stein is recommended, as it is uniform, allows data comparison from different centers, and is important for the stratification of patients in prospective studies.
  • Type I tumour-AC of the distal oesophagus, the centre of the tumour lying 1–5 cm above the anatomical cardia.
  • Type II tumour- AC of the cardia with its centre situated between 1 cm above and 2 cm below the anatomical cardia;
  • Type III tumour is a gastric carcinoma with its centre between 2 and 5 cm below the anatomical cardia.
• Staging CT scan of chest, abdomen and pelvis for distant metastasis
• EUS for loco regional staging (T, N staging)
• Laparoscopy may be needed where there is suspicion of peritoneal spread on CT or EUS such as in the presence of small volume ascites.

TNM staging

T1- Tumor invades lamina propria or submucosa (a-lamina propria, b-submucosa) T2- Tumor invades muscularis propria T3- Tumor invades adventitia T4- Tumor invades adjacent structures N1- Regional lymph node metastasis M1- Distant metastasis

Stage I- T1N0M0 Stage IIa- T2T3/N0M0 Stage IIb- T1T2/N1M0 Stage III- T3N1M0, T4, any N, M0 Stage IV- M1

• Tumours of lower thoracic oesophagus- M1a- coeliac nodes involvement, M1b- Other distant metastasis
• Tumours of the mid thoracic oesophagus: M1a- not applicable. M1b- Non regional lymph nodes and/or other distant metastasis
• Tumours of the upper thoracic oesophagus: M1a- Metastasis in cervical nodes M1b- Other distant metastasis.

Management of resectable tumours

Who are surgical candidates?

• Radical surgery is recommended for patients with localised (T1, T2) tumours that are sufficiently fit to tolerate the procedure.
• Combination therapy should be considered for T2 tumours. Preoperative chemotherapy (2 cycles of cisplatin and 5FU) for all patients with operable oesophageal cancer other than those with unequivocally T1 tumours provides a gain in median and two-year survival compared to surgery alone. This is thus the standard of care in the UK based upon the MRC trials. There is no evidence to support the use of preoperative radiotherapy in oesophageal cancer.
• Patients with advanced oesophageal cancer (T3N1) should be considered for RCTs to assess the role of novel multimodality therapies in combination with surgery.

What is the type of surgery needed?

Patients with either AC or SCC involving the middle or lower third of the oesophagus generally require total oesophagectomy because of the risk of submucosal skip lesions. The most popular methods used are the transhiatal and transthoracic (Ivor-Lewis) approaches. Gastric interposition is most commonly used as a conduit for reconstruction following oesophagectomy.
A radical two-field (abdominal and thoracic) lymph node dissection is also undertaken. Japanese do a three field (including neck) lymph node dissection.

What are the risks of surgery?

Clinical anastomotic leakage should not exceed 5%. Curative (R0) resection rates should exceed 30%. Overall hospital mortality for oesophageal resection should be less than 10%.

What is the prognosis?

Five year survival rate is over 80% when tumours are confined to the mucosa and between 50% and 80% when the submucosa is involved.

What is the role of adjuvant chemotherapy?

There is no evidence for a role of adjuvant chemotherapy in oesophageal cancer. However, for patients with completely resected node-positive disease who have not received neoadjuvant therapy, postoperative adjuvant chemotherapy should be considered, although whether chemotherapy alone or chemoradiotherapy should be used is unclear.

Is there any role of chemo-radiation?

• Chemoradiation is the definitive treatment of choice for localised squamous cell carcinoma of the proximal oesophagus.
• Carcinoma of the cervical esophagus (6-8 cms long from cricopharyngeus till thoracic inlet) presents a unique management situation. Radiation combined with chemotherapy is generally preferred over surgery since long-term survival appears to be similar, and major morbidity is avoided in most.

What is the role of local treatments?

All submucosal tumors have a substantial risk of lymph node metastases. Local lymph node invasion occurs early and quickly because the lymphatics in the oesophagus are located in the lamina propria, in contrast to the rest of the gastrointestinal tract, in which they are located in the submucosa. Hence, local treatments like Endoscopic mucosal resection (EMR) and photodynamic therapy (PDT) may be considered in selected patients (especially poor surgical risk patients) as potentially curative options for superficial oesophageal cancer, confined to the mucosa.

Who is fit for surgery?

The previous medical history and concurrent morbidity remain the strongest predictors regarding fitness for surgery. Pre-existing ischaemic heart disease, poorly controlled hypertension, and pulmonary dysfunction are all associated with increased operative morbidity. The American Society of Anaesthesiologists (ASA) classification of physical status is well recognised. Perioperative risk increases with increasing ASA score. Only those patients with an ASA score of 3 or less should be considered for surgery.

How do you follow up these patients post treatment?

There is little consensus for the mode, duration, or intensity of follow up in patients with malignant disease. There is no evidence that intensive follow up improves the speed of detection of recurrent disease in oesophageal or gastric cancers. However, majority of patients prefer regular follow up.

Management of unresectable oesophageal cancer

What is an unresectable tumour?

• Any T4 lesion
• Any M lesion with the exception of coeliac nodes for distal adenocarcinomas.

The current staging system for oesophageal cancer is based largely on retrospective data from the Japanese Committee for Registration of Oesophageal Carcinoma. It is most applicable to patients with SCC of the upper- and middle-thirds of the oesophagus, as opposed to the increasingly common distal oesophageal and GO junction adenocarcinomas. In particular, the classification of involved abdominal lymph nodes as M1 disease has been criticized. The presence of positive abdominal lymph nodes does not appear to carry as grave a prognosis as metastases to distant organs. Patients with regional and/or coeliac axis lymphadenopathy should not necessarily be considered to have unresectable disease due to metastases. Complete resection of the primary tumor and appropriate lymphadenectomy should be attempted when possible.

What are the Palliative options for unresectable disease?

1. First line treatment-

Combined chemoradiotherapy should be first line of treatment as this offer a small but real chance of sustained disease control and long term survival. Approximately 60% of patients would be dysphagia free till death. However, the time to onset of improvement of dysphagia is slow. In a study, median time to improvement in symptoms was two months after radiotherapy, variable but prolonged after chemotherapy, and immediate after stent insertion.

Who is fit for chemotherapy?

Fitness for chemotherapy is generally assessed by using The World Health Organisation performance scale. It has categories from 0 to 4. 
0 – fully active patient.
1 – cannot carry out heavy physical work, but can do anything else.
2 – up and about more than half the day; can look after himself, but not well enough to work.
3 – in bed or sitting in a chair for more than half the day; need some help in looking after him
4 – in bed or a chair all the time and need a lot of looking after
Good performance status is 0 or 1. Poor performance status is 2-4.
Generally patients are considered fit for chemotherapy with good performance status (PS0, PS1). Good PS2 (leaning towards PS1) are also generally considered fit for chemotherapy

2. Endoscopic palliation may be appropriate for palliation of dysphagia in patients awaiting definitive treatment or patients unfit for chemoradiotherapy.
   1. Covered expandable metal stents is the treatment of choice. They are also the treatment of choice for malignant tracheoesophageal fistulation or following oesophageal perforation sustained during dilatation of a malignant stricture. The tumour should be more than 2 cm from the cricopharyngeus for stenting.
   2. Dilatation alone should be reserved for patients who are considered to have an extremely short life span (four weeks or less) and unable to swallow saliva, or as a very short term measure to relieve dysphagia while more definitive treatment is planned. Most malignant strictures can be safely dilated to 16 or 17 mm in several sessions. However, repeat dilatation is usually required every two to four weeks.
   3. Laser or APC- consider it in short segment cardia tumours- where a stent would have a high risk of migration/displacement. APC/Laser could also be used for tumour overgrowth at the end of stents. Treatments are performed every other day and are usually completed in three to four sessions (one week). Relief may last for one to several months and treatments may have to be repeated. Further, Laser therapy or judicious and careful use of oesophageal dilatation is widely held to be the best form of palliative treatment for cervical oesophageal tumours within 2 cm of the upper oesophageal sphincter.

Survival

Reported five-year survival rates for stages I to IV disease are 60, 31, 20, and 4 percent, respectively.

Table 1. ASA Scores.
Class	Physical status	Example
I	A completely healthy patient	A fit patient with an inguinal hernia
II	A patient with mild systemic disease	Essential hypertension, mild diabetes without end organ damage
III	A patient with severe systemic disease that is not incapacitating	Angina, moderate to severe COPD
IV	A patient with incapacitating disease that is a constant threat to life	Advanced COPD, cardiac failure
V	A moribund patient who is not expected to live 24 hours with or without surgery	Ruptured aortic aneurysm, massive pulmonary embolism
E	Emergency case

Normal oesophageal structure:

1. Mucosa-
   1. Nonkeratinized stratified squamous epithelium
   2. Lamina propria- loose network of connective tissue in which blood vessels, scattered lymphocytes,macrophages and plasma cells
   3. Muscularis mucosae- thin layer of circular muscle between lamina propria and submucosa
2. Submucosa- dense network of connective tissue containing blood vessels, lymphatic channels, Meissner’s plexus and oesophageal glands
3. Muscularis propria- inner circular layer, Auerbach’s myenteric plexus and outer circular layer
4. Adventitia-

Ref:

1. British Society of Gastroenterology Guidelines for the management of Oesophageal and gastric cancer
2. http://cancerweb.ncl.ac.uk/cancernet/100089.html

Self assessment

1. Alcohol is an important risk factor for oesophageal adenocarcinoma
2. Oesophageal carcinoma tend to metastasis early
3. Oesophageal lymphatics are situated in the mucosa
4. T4 tumours are unresectable
5. Performance stage 3 patients are generally fit for chemotherapy
6. Siewert and Stein type III tumour is an oesophageal adenocarcinoma
7. Achalasia increases the risk of oesophageal adenocarcinoma
8. M1a (coeliac node positive) for distal oesophgeal carcinoma is unresectable
9. Neoadjuvant chemotherapy should be considered for T1 tumours
10. ASA class III patients can be offered oesophageal surgery.

Answers :
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