Oesophageal cancer is the 14th most common malignancy in the UK. There are two major types - squamous cell carcinoma and adenocarcinoma. The main risk factors are smoking, alcohol consumption, and chronic reflux. Symptoms include dysphagia. Diagnosis involves endoscopy with biopsies. Treatment depends on staging and may include surgery, chemotherapy, radiotherapy, or palliative care. Prognosis is poor with a 5-year survival of around 16% but depends on stage, with early-stage disease having a better prognosis if treated.

1. z Yahya Berke DEMIREL
Odessa National Medical University
1st Group
5th Course

2. z
Oesophageal cancer is the 14th most common malignancy in adults in the UK.
 The oesophagus is a muscular tube that is situated within the thorax and runs from the
pharynx to stomach. It is pivotal in the transfer of food material to the stomach and
broadly divided into upper, middle and lower.
 There are two major types of cancer that arise from the oesophagus, depending on the
cell of origin.
• Squamous cell carcinoma (SCC): usually located in the upper or middle oesophagus.
Accounts for >90% of cases worldwide.
• Adenocarcinoma (AC): usually located in the lower oesophagus. Due to chronic reflux
and development of a columnar metaplasia, which is a precursor lesion known
as Barrett’s oesophagus.
 Rarer forms of oesophageal cancers include small cell carcinoma, sarcoma, lymphoma,
melanoma and choriocarcinoma.
 The hallmark clinical feature of oesophageal cancer is dysphagia, which refers to
difficulty swallowing. This is due to obstruction of the oesophageal lumen.

3. z
Epidemiology
 The incidence of oesophageal adenocarcinoma, particularly at
the gastro-oesophageal junction, has increased dramatically.
 Oesophageal cancer is rare in young people and more common
as we age. The peak incidence is seen in the 7-8th decades.
 Globally, SCC is the most common cause of oesophageal
cancer, but the incidence of AC is increasing, particularly in
Western countries. This is due to an increase in AC risk factors
such as obesity.
 AC is more commonly seen in men, whereas the male-to-female
ratio is more equal in SCC.

4. z
Etiology
 Smoking and alcohol consumption are the two major risk factors
for the development of SCC.
 Oesophageal neoplasia develops due to sequential mutations
that occur in the oesophageal epithelium, which allows cells to
proliferate uncontrollably. Several risk factors for both SCC and
AC increase the likelihood of developing these mutations.

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 Squamous cell carcinoma
 The biggest risk factors for development of SCC include alcohol
consumption and smoking.
• Smoking
• Alcohol consumption
• Foods containing N-nitroso compounds
• Chewing of areca nuts
• Previous partial gastrectomy
• Atrophic gastritis
• Human papillomavirus (HPV): mainly genotypes 16 and 18
• Tylosis: rare condition leading to hyperkeratosis of hands and feet
Squamous cell carcinoma of the esophagus

6. z
 Adenocarcinoma
 The majority of AC cases arise from Barrett’s oesophagus, which refers to
columnar metaplasia of the lower oesophagus due to chronic reflux. This a
pre-malignant lesion.
• Chronic reflux
• Barrett’s oesophagus: 30-fold increase risk of AC
• Smoking
• Obesity
• Zollinger-Ellison syndrome: gastrin-secreting tumour leading to excess
hydrochloric acid.

7. z
T1a adenocarcinoma of esophagus with
further subdivision according to the depth pf
invasion.

8. z
Pathophysiolog
y
 The majority of oesophageal SCCs arise from the mid-
oesophagus and ACs from near the gastro-oesophageal junction
(GOJ).
 Squamous cell carcinoma
 The majority of SCCs occur due to chronic alcohol consumption and
smoking, which damage cellular DNA. This leads to development of
genetic mutations that promote abnormal cell growth. Overtime, the
cells proliferate uncontrollably leading to invasive cancer.
 SCC may be seen as an infiltrating and ulcerated mass in the middle
oesophagus, especially if advanced. There is early invasion into
surrounding lymph nodes and the tumour may metastasize to liver,
bone and lung.

9. z
 Adenocarcinoma
 Typically, chronic reflux leads to inflammation and damage of the lower
oesophageal mucosa. This results in columnar metaplasia, which refers
to the transformation of the mature squamous cell type to columnar cell
type.
 This metaplastic epithelium may become dysplastic, which refers to
cells with abnormal growth and development. The dysplastic epithelium
acquires further genetic mutation that promotes development of
invasive carcinoma. AC is most commonly located near the GOJ and
there is usually early lymph node involvement.

10. z
 The hallmark feature of oesophageal cancer is dysphagia, which refers to difficulty
swallowing.
 Symptoms
• Constitutional symptoms: fevers, anorexia, lethargy, weight loss
• Dysphagia: difficulty swallowing
• Weight loss: due to tumour-related anorexia and poor nutrition from swallowing difficulties
• Bleeding: haematemesis and melaena
• Pain: typically retrosternal pain
• Aspiration: cough, shortness of breath, fever
• Hoarseness: if there is extension to involve the recurrent laryngeal nerve
Clinical features

11. z
 Signs
• Lymphadenopathy: if local tumour spread
• Cachexia
• Pallor: due to anaemia
• Hepatomegaly: if metastatic spread

12. z
Suspected cancer
referral
 The NICE (NG12) guideline outlines recommendations for the referral of suspected
cancer cases including upper gastrointestinal cancers. Below details the
recommended referral for suspected oesophageal cancer.
 Urgent (two week wait) referral
 This means referring a patient for appropriate investigations (e.g. gastroscopy) for
suspected oesophageal cancer within two weeks. It is usually combined with a clinic
appointment and CT imaging.
• Dysphagia, OR
• > 55 years with weight loss and one of the following:
• Upper abdominal pain
• Reflux
• Dyspepsia

13. z
 Non-urgent referral
 This means referral for a non-urgent gastroscopy to assess for oesophageal
pathology. Usually performed within 6 weeks.
• Haematemesis, OR
• > 55 years with treatment resistant dyspepsia, OR
• > 55 years with upper abdominal pain and anaemia, OR
• Thrombocytosis with one of the following:
• Nausea/vomiting
• Weight loss
• Reflux
• Dyspepsia
• Upper abdominal pain

14. z
• Nausea/vomiting with one of the following:
• Weight loss
• Reflux
• Dyspepsia
• Upper abdominal pain
 NOTE: Upper and lower gastrointestinal (GI) investigations should
also be considered to investigate for GI malignancy (inc.
oesophageal cancer) in all postmenopausal female and male
patients where IDA has been confirmed unless there is a history of
significant overt non-GI blood loss. According to British Society of
Gastroenterology guidelines 2011.

15. z
Diagnosi
s
 Oesophageal cancer is diagnosed using upper GI endoscopy
and biopsies of suspected lesions.
 The principle test for the diagnosis of oesophageal cancer is an
upper GI endoscopy known as a gastroscopy. This a camera
test that allows direct visualisation of the upper gastrointestinal
tract including oesophagus and gastro-oesophageal junction.

16. z
Oesophageal cancer seen at endoscopy

17. z
Investigations
 Further investigations allow assessment of distant spread and key-organ
function to help guide management.
 Bloods
• Full blood count
• Serum iron, transferrin saturation, total iron binding capacity (TIBC)
• Urea & electrolytes
• Liver function tests
• Bone profile
• Clotting screen
• Renal function

18. z
 Imaging
• CT chest/abdomen/pelvis: patients with suspected oesophageal
cancer undergo CT imaging to help stage the cancer. See
staging below.
• Abdominal ultrasound: may be used to assess for liver
metastasis. Usually superseded by CT.
• PET-CT: offered to patients with potentially resectable disease
(i.e. candidates for surgery) to assess for distant disease not
detected by conventional CT.

19. z

20. z
 Special
• Gastroscopy: principle investigation for diagnosis.
• Endoscopic ultrasound (EUS): can be performed at time of endoscopy.
Sometimes completed to help more accurately stage oesophageal cancer
if it will change management.
• Diagnostic laparoscopy: may be used to more accurately stage
oesophageal cancer if it will alter management.
 HER2 testing
 Human epidermal growth factor receptor 2 (HER2) testing should be
completed on tumour or biopsy specimens. Targeted therapy against the
HER2 receptor may be offered to patients with HER2 positive metastatic
oesophageal cancer.

21. z

22. z
Staging
 Tumour
• TX: Primary tumour cannot be assessed
• T0: No evidence of primary tumour
• Tis: Carcinoma in situ/high-grade dysplasia
• T1: Tumour invades lamina propria or submucosa
• T1a: Tumour invades mucosa or lamina propria or muscularis mucosae
• T1b: Tumour invades submucosa
• T2: Tumour invades muscularis propria
• T3: Tumour invades adventitia
• T4: Tumour invades adjacent structures
• T4a: Tumour invades pleura, pericardium, diaphragm or adjacent peritoneum
• T4b: Tumour invades other adjacent structures such as aorta, vertebral body or trachea

23. z
 Node
• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1: Metastasis in 1–2 regional lymph nodes
• N2: Metastasis in 3–6 regional lymph nodes
• N3: Metastasis in 7 or more regional lymph nodes
 Metastasis
• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1: Distant metastasis
 NOTE: Non-regional lymph node spread is considered M1a disease.

24. z
Management
principles
 Treatment options
 There are numerous treatment options for the management of oesophageal cancer:
• Surgery: resection of oesophageal or gastro-oesophageal tumours (e.g. oesophagectomy).
• Endoscopic techniques: mucosal resection or mucosal dissection.
• Radiotherapy: use of high energy rays to destroy cancer cells.
• Chemotherapy: use of anti-cancer medications to destroy cancer cells.
• Targeted cancer drugs: monoclonal antibodies against certain receptors (e.g. HER2).
• Palliative care: use of chemotherapy/radiotherapy or stenting to control disease
and/or symptoms without aiming to cure.
• Best supportive care: focus primarily on symptoms and quality of life without systemic
treatments.

25. z
 Determining choice
 The choice of treatment depends on whether the cancer is limited,
locally advanced or advanced/metastatic.
• Limited: refers to small tumours without lymph node involvement or
distant spread
• Locally advanced: refers to larger tumours with/without lymph node
involvement but without distant spread
• Advanced/metastatic: refers to metastatic disease with spread to
distant sites

26. z
Limited and locally
advanced
 The treatment of choice for limited disease is surgical or
endoscopic resection.
 Surgical resection, radiotherapy, chemotherapy, or a
combination, may be used for patients with limited or locally
advanced disease.
• Limited disease (Staging: T1-2, N0, M0)
• Locally advanced disease (Staging: T3-4 or N1-2, M0)

27. z

28. z
 Surgery
 Surgical resection of oesophageal cancer is the treatment of choice if the patient is fit to
undergo an operation and the disease is limited. Surgery may be an option for patients
with locally advanced oesophageal cancer. This can be considered following systemic anti-
cancer therapy (e.g. chemoradiotherapy). The idea is to shrink the tumour, which then
becomes resectable.
 The surgical technique of choice is an oesophagectomy, which refers to removal of part of
the oesophagus and subsequent joining of the remaining oesophagus to the stomach. If
the tumour involves the GOJ or proximal stomach then an oesophago-gastrectomy or
extended total gastrectomy may be undertaken. In addition to surgical removal of the
oesophagus, lymph node dissection may be considered at the time of surgery.
 Surgical resection is an option for:
• Limited disease
• Locally advanced disease (deemed resectable following neoadjuvant chemoradiotherapy)

29. z
 Endoscopic therapy
 Patients with limited disease may be suitable for endoscopic
therapy to remove the oesophageal cancer.
 Two options include:
• Endoscopic mucosal resection (EMR)
• Endoscopic submucosal dissection (ESD)
 These are typically performed in specialist upper gastrointestinal
centres any may require preoperative assessment with endoscopic
ultrasound (EUS) to ensure no localised lymph node spread.

30. z
 Systemic anti-cancer therapy
 The two main systemic anti-cancer therapies used in both SCC and AC
are chemotherapy and radiotherapy.
• Squamous cell carcinoma: a combination of chemotherapy (e.g.
cisplatin/5-fluorouracil) and radiotherapy may be given as neoadjuvant
therapy to shrink the tumour prior to resection or as definite treatment.
SCC is highly chemo/radio sensitive, which is why it can be used as
radical therapy. Patients undergoing radical chemoradiotheray are
followed-up regularly to assess whether a salvage resection should be
undertaken.
• Adenocarcinoma: either chemotherapy (e.g. cisplatin/5-fluorouracil) alone
or in combination with radiotherapy should be given to patients as
neoadjuvant therapy. If there is a response to treatment and the tumour
shrinks becoming resectable on restaging then surgical intervention should
be considered. Radial chemoradiotherapy (i.e. main treatment to cure
cancer) is not an option in AC.

31. z
 Palliative management
 Palliative treatment should be considered in patients with locally advanced
disease who are not operative candidates or not fit enough to undergo
radical treatment (e.g. poor performance status, extensive co-morbidities).
 Options include:
• Radiotherapy: if tumour lies within a radiotherapy field that allows high-
doses to be applied.
• Chemotherapy: regimens depend on fitness of the patient.
• Local tumour treatment: endoscopic stenting, palliative radiotherapy.
• Best supportive care: focusing on symptom control only.
 NOTE: oesophageal stenting involves endoscopically placing a stent within
the oesophagus to keep the lumen open and prevent dysphagia.

32. z
 Nutritional support
 Patients being considered for radical treatment (e.g. surgical
resection or chemoradiotherapy) need to have their nutrition
optimised. This may mean temporary enteral or parenteral
nutrition.
 In patients undergoing chemoradiotherapy, they should be
considered for enteral nutrition with placement of a radiologically
inserted gastrostomy (RIG) tube. This is because
chemoradiotherapy will damage the oesophagus leading to
localised inflammation during treatment that will impair nutritional
intake. A percutaneous endoscopic gastrostomy (PEG) is not
suitable in these cases due to the risk of tumour migration from
endoscopic pull through of the tube.

33. z
Prognosis
 The five year survival of oesophageal cancer is poor at ~16%
 Survival from oesophageal cancer depends on stage. The five
year survival for stage 1 disease is 52.8% but only 16% for
stage 3 disease. Early diagnosis and treatment is potentially
curative, especially if the disease is resectable. However,
oesophagectomy is a major operation with significant morbidity
and mortality.

34. z
Prepared by: Yahya Berke DEMIREL
ONMU
1st Group
5th Course