Esophageal Cancer

Question 1

What is esophageal cancer?

Answer 1

Malignancy of esophagus, mostly SCC or adenocarcinoma

Question 2

What is the epidemiology of esophageal cancer?

Answer 2

Age >60, males>females 10th most common cause of cancer death SCC - 3.85/100K in males, 0.81/100k in females Adenocarcinoma - 0.5/100k in males, increasing due to GERD and obesity

Question 3

What are the risk factors for esophageal cancer?

Answer 3

Common risk factors - Age, gender, family history SCC and AC have differing risk factors

Question 4

What are the risk factors for SCC

Answer 4

Race - African/American, esophageal belt of china/africa Males Alcohol and smoking Hot beverages, nutritional deficiencies, betel nut, nitrosamine ingestion Achalasia, caustic injuries, HPV, radiotherapy, esophageal diverticulum and webs, Plummer Vinson syndrome

Question 5

What are the risk factors for AC?

Answer 5

White race Males Smoking (Not alcohol) Obesity Chronic GERD/Barrett’s esophagus

Question 6

What is the pathology of SCC esophagus?

Answer 6

1. Can arise anywhere, but typically found in middle third 2. Exophytic fungating growth, 25% ulcerative, 15% infiltrative 3. Development - Dysplasia -> Ca is -> Invasive SCC -> Metastatic disease

Question 7

What is the pathology of AC esophagus?

Answer 7

1. Distal third 2. Malignancy with glandular differentiation that arises in the background of chronic GERD 3. Metaplasia -> dysplasia ->adenocarcinoma

Question 8

What is the clinical presentation of esophageal cancer?

Answer 8

Most patients with early-stage disease are asymptomatic or may have symptoms of reflux, non-specific i.e. retrosternal discomfort, “indigestion”. However, approximately 50% of patients have unresectable lesions or distant metastasis on presentation. 1. Rapidly progressive dysphagia (first and most common presentation) – fluid and soft food better tolerated than hard/bulky food 2. Odynophagia (20%): pain develops late, usually due to extra-esophageal involvement 3. Weight loss: secondary to reduced appetite, malnutrition and active cancer 4. Regurgitation of saliva or undigested food (without gastric acid): secondary to tumour disrupting normal peristalsis and causing esophageal obstruction (risk of aspiration pneumonia) 5. Anemia (with or without melena/frank hematemesis – bleeding is usually occult): tumour surface may be fragile and bleed

Question 9

What are the features of complicated esophageal Ca?

Answer 9

Locally advanced 1. Bleeding 2. Obstruction 3. Hoarsness 4. Horner’s syndrome (invasion of brachial plexus) 5. Respiratory symptoms (Trachea-esophageal fistula) Systemic - SCC will spread through thorax, AC spreads through abdomen Nodes - supraclavicular, gastric/celiac Bone - Back/bone pain Liver - RHC pain, ascites, jaundice Lung - Hemoptysis, cough, SOB, pleural effusion Others - adrenals, cutaneous, muscle brain (Rare)

Question 10

What are the modes of spread of esophageal Ca?

Answer 10

Direct extension into surrounding regions (trachea, pericardium) Lymphatic spread along submucosal lymphatic channels Hematogenous spread to liver, lung adrenal glands and kidney

Question 11

What lymphatics drain the esophagus?

Answer 11

Superior 1/3 - Deep cervical Middle 1/3 - Mediastinal Inferior 1/3 - Gastric and celiac

Question 12

What investigations are required for esophageal Ca?

Answer 12

1. OGD with biopsy Circumferential, fungating, sloughy, obtsructive, ulcerative lesion Biopsy of specimen to confirm - Diagnosis - Simultaneous lesions in stomach (needed for esophagectomy) - Lumen diameter -Barrett’s -Measurement of tumour location and extent 2. Barium swallow (less invasive) - Can access tumour complications like tracheo-esophageal fistula -Access for proximal dilatation, mucosal irregularities or constrictions -Low diagnostic rate Less commonly performed

Question 13

What are the staging studies for confirmed esophageal Ca?

Answer 13

1. CT TAP +/- Neck 2. Endoscopic ultrasound + FNA 3. PET scan with CT scan 4. Surgical laparascopic staging

Question 14

What are the findings for CT TAP/Neck?

Answer 14

Modality of choice for staging distant metastasis, If proximal tumour, include CT neck ▪ Can be used for T, N, and M staging - Nodes > 10mm are considered to be metastatic - Nodal involvement outside area of resection (i.e. supraclavicular or paraaortic lymph nodes – M1 disease) – contraindication to esophagectomy ▪ CT Thorax - Presence of any lung metastases - Aspiration pneumonia – pleural effusion, collapse, consolidation - Pleural and/or pericardial effusion - Tracheal deviation or extrinsic compression of tracheobronchial system - Widened superior mediastinum in an upper oesophageal tumour - Raised hemi-diaphragm with phrenic nerve involvement - Any chronic respiratory conditions

Question 15

What are the findings for EUS?

Answer 15

Endoscopic ultrasound (EUS) +/- FNA ▪ EUS combines endoscopy with high frequency ultrasound within the oesophageal lumen which allows for high resolution image of the tumour, the oesophageal wall and adjacent structures ▪ EUS is good for T staging of small tumours (determine depth of wall invasion), and N staging (identify malignant (>10mm, sharp borders, hypoechoic, homogenous) lymph nodes) ▪ Role in early stage esophageal cancer, if endoscopic resection is feasible

Question 16

What are the findings of PET Scan in esophageal Ca?

Answer 16

Positron Emission Tomography with integrated CT Scan (PET/CT)* ▪ Essential, most useful test to r/o distant metastatic disease (identified in ~20% if patients who are free of metastases on CT / EUS to prevent unnecessary high morbidity surgery) ▪ Essential staging investigation in identification of distant metastases not evident on CT ▪ Can also be used for assessing recurrence or re-staging after neoadjuvant therapy

Question 17

What are the surgical laparascopic staging findings in esophageal Ca?

Answer 17

Surgical Laparoscopic Staging (most beneficial for patients with adenocarcinoma) (controversial) ▪ For patients with distal esophageal tumour who appear free of distant metastases on CT scan (T3-T4) ▪ Can r/o occult liver metastasis and peritoneal carcinomatosis not evident on CT scan ▪ Peritoneal lavage also performed at time of laparoscopy

Question 18

What tests are run to measure complications of the disease?

Answer 18

Blood Tests ▪ FBC: low hemoglobin (anemia from chronic blood loss), raised TW (? aspiration pneumonia) ▪ U/E/Cr: electrolyte derangement for vomiting, poor oral intake ▪ LFTs: low albumin with nutritional deprivation 2. Rigid Bronchoscopy with biopsy and brush cytology ▪ For patients with supracarinal primary tumours and suspicion of airway involvement (trachea-oesophageal fistula) ▪ Patients with tracheo-oesophageal fistula are not for surgery. For palliative care (survival ~6 months) 3. Laryngoscopy: assess vocal cord paralysis

Question 19

What are the pre operative investigations to be carried out?

Answer 19

1. Blood tests - Full blood count - Liver function test - Prothrombin/INR/aPTT - Group cross match 2. Cardiac investigations -ECG, 2D echogram 3. Respiratory investigations - Lung function test to ensure patient can tolerate single lung ventilation during op

Question 20

What is the TNM Staging for Esophageal Ca?

Answer 20

Question 21

What is the management of esophageal Ca?

Answer 21

Multimodal approach of

1. Surgery
2. Chemotherapy
3. Radiotherapy

Exceptions are for very early disease which can be managed with endoscopic resection and for metastatic disease which is palliative

Question 22

What is the approach to selection of treatment modality?

Answer 22

1. Staging
2. Obstruction
3. Localized disease
4. Neoadjuvant therapy

Question 23

How does the stage of esophageal cancer affect managment?

Answer 23

1. Very early tumours (Tis, T1a) → endoscopic submucosal dissection (ESD)

Advocated for early cancers such as T1a (mucosa)
▪ T1a tumours have 1-5% chance of LN spread as compared to T1b tumours (involve submucosa) which have 17-20% risk
of LN spread
▪ ESD better than EMR in terms of recurrence rates, curative rates with equivalent rates of complications (perforation, stricture,
bleeding)

2. Tumour confined to oesophagus (T1b, T2) → controversial can either do upfront surgery or neoadjuvant chemoRT
   (adenocarcinoma) → at present, current staging modalities are not reliable to confidently stage tumours clinically as T2
3. Locally advanced tumours (T3-4, N1-3) → multimodal therapy with neoadjuvant chemoRT or neoadjuvant chemotherapy
   followed by surgical resection
   - Upfront esophagectomy has high rates of recurrence and low 5 year survival, hence multi-modality therapy preferred
   - Depending on histology, SCC and Adenocarcinoma have different sensitivities to radiotherapy
4. Metastatic Disease (M1) → palliative treatment (endoscopic methods to treat malignant dysphagia or fistulous disease)
   ▪ Malignant dysphagia (M1) → expandable oesophageal stent or RT (for GEJ cancer, as stents leads to severe GERD)

Question 24

When is feeding done in esophageal Ca?

Answer 24

Feeding via PO route is preferred unless the passage is obstructed (i.e. risk of aspiration)
- If still able to pass NG tube around tumour, then feed via NG (but also consider complications with long-term NG placement e.g.
erosions around nasal area, sinusitis); consider PEG placement* for long-term feeding if able to get scope around tumour
- If unable to pass tube or scope around tumour, consider total parenteral nutrition or open gastrostomy
- Relief of obstruction via endoscopic stenting and/or radiotherapy helps to enable oral feeding, but most techniques are not longlasting
and dysphagia will return with tumour growth

Question 25

What the neoadjuvant therapy for esophageal Ca?

Answer 25

Long-term survival advantage with the use of trimodal therapy with neoadjuvant chemoradiotherapy followed by surgery in the
treatment of oesophageal cancer as compared to surgery alone
- Varying sensitivities between SCC and Adenocarcinoma with radiotherapy hence different centres have different neoadjuvant
approaches
- Some centres practice neoadjuvant chemoRT for SCC and neoadjuvant or peri-operative chemotherapy (i.e. chemotherapy
before and after surgery) for adenocarcinoma

Question 26

What are the broad types of esophagectomies?

Answer 26

Transthoracic and trans-hiatal

Question 27

What are the types of transthoracic esophagectomies?

Answer 27

Ivor Lewis (2-stages) which involves gastric mobilisation (first stage, done through upper midline abdominal incision),
oesophagectomy, extended lymphadenectomy and intra-thoracic esophagogastric anastomosis (second stage, through
right posterolateral thoracotomy)
▪ McKeown (3-stages) which involves right posterolateral thoracotomy or thoracoscopy, then abdominal (via laparotomy)
and then cervical portion (for cervical esophagogastric anastomosis via left neck incision)
▪ Minimally invasive esophagectomy (MIE)* – can be total MIE, hybrid MIE or robotic MIE

Question 28

What is a transhiatal esophagectomy?

Answer 28

▪ Two incisions – one in the abdomen (via upper midline laparotomy) and one in the neck (left neck incision)
▪ Avoids thoracotomy and involves a cervical esophagogastric anastomosis
▪ Blunt esophagectomy(removal of oesophagus), gastric mobilisation with creation of neo-oesophagus* (gastric conduit) and
cervical esophagogastrostomy (translocation of the stomach)
▪ Less morbidity than Ivor-Lewis as the chest is not opened
▪ The colon or jejunum can also be used if the stomach is not a suitable conduit

But it is sub optimal as there is no lymph node clearance

Question 29

What is the management of a patient post esophagectomy?

Answer 29

1. Analgesia – IV or epidural (i.e. morphine or bupivacaine)
2. Gastrointestinal
   ▪ NBM – 5 to 7 days
   ▪ Jejunostomy feeding tube – placed during surgery and start feeding on POD 2-3
   ▪ NG tube on low level intermittent suction
   ▪ Gastrografin swallow – day 5 to 7 to check for anastomotic leak before initiating oral intake, can also add blue dye to check
   for leakage of dye into chest tube suggesting anastomotic leak
   ▪ Escalation of feeds as tolerated – aim for 6 to 8 small frequent meals each day
3. Prevention of complications
   ▪ Early mobilization (sit out of bed from post op day 1)
   ▪ Aggressive Pulmonary Rehabilitation (i.e. incentive spirometry, chest physiotherapy)

Question 30

What is the indication for palliative treatment for esophagectomy?

Answer 30

The aim is to relieve obstruction and dysphagia

Indication:
▪ Metastatic oesophageal cancer (M1)
▪ Cancer with invasion of adjacent organs (T4b)
▪ Aortic oesophageal fistula (~100% lethal)
- > 50% of patients at presentation is only suitable for palliative treatment
- Nutritional support with percutaneous endoscopic gastrostomy (PEG) or jejunostomy tube (PEJ)
- 2 arms of treatment (local treatment - treat dysphagia, and systemic treatment)

Question 31

What is the local palliative treatment for esophageal Ca?

Answer 31

Endoscopic Intraluminal Prosthesis
▪ Mostly only pureed diet tolerated
▪ Self-expanding metal stents (i.e. SEMS, uncovered metal stent) preferred over plastic stents
▪ Procedural related mortality ~ 1-2%, early complication rates ~ up to 30%
- Risk of perforation, malposition, incomplete stent expansion, migration of stent (1%), obstruction of tube by food,
tumour ingrowth or overgrowth
- Pyloric stents may be used as first line treatment in patients with poor prognosis requiring palliation of gastric outlet
obstruction. If patient is fit with longer life expectancy, can consider gastro-jejunostomy

External Beam Radiotherapy (EBRT)
▪ Compared to stenting, EBRT have slower relief of dysphagia, but is effective for patients whose tumour are bleeding
▪ Palliation of dysphagia is successful temporarily in 80% of patients but rarely provide relief for longer than several months
▪ Usually given in combination with palliative chemotherapy

Question 32

What are the systemic palliative treatments for esophageal Ca?

Answer 32

Chemotherapy
- Targeted Therapy → herceptin (for patients with Her-2 overexpression)

Question 33

What are the complications of surgical intervention for esophageal Ca?

Answer 33

Cardiovascular Complications: post-esophagectomy atrial fibrillation, AMI / VTE
- Pulmonary Complications: atelectasis, pneumonia, ARDS
- Oesophageal anastomosis complications: anastomotic leak and resultant mediastinitis (chest anastomosis), anastomotic
strictures secondary to healed anastomotic leaks, conduit Ischemia
- Gastric Outlet Obstruction (transected vagal nerve)
- Other local traumatic complications: chylothorax (can be low or high volume), bleeding, injury to recurrent laryngeal nerve

▪ Low volume chylothorax (<500ml/day), manage conservatively (i.e. enteral intake with medium chain TG, NBM with parental
nutrition ±octreotide), if chylothorax persists – consider talc pleurodesis

▪ High volume chylothorax (>1000ml/day), thoracic duct embolization or thoracic duct ligation or talc pleurodesis