Oesophageal cancer

Section: UGI Sub-section: Oesophagus Curriculum: Curriculum, page 94

Definition

Malignant neoplasia of the oesophagus, which is mostly carcinoma

Incidence

• Uncommon (< Pancreatic Ca!)
• M > F (SCC 3:1, adenocarcinoma 7:1)
• Occurs in 5th-7th decades of life
• SCC more common than adenocarcinoma
  • Incidence of adenocarcinoma increasing
  • Esp. in White men → ~ 50:50
• Incidence of SCC in Western countries decreasing
  • 5 / 100,000 in US/UK
  • Most common in China (100 / 100,000), Singapore, Iran, Russia, S Africa

Classification

• Histologic
  • SCC
    • Further sub-classified on histology type
  • Adenocarcinoma
  • Undifferentiated
  • Other
• Location
  • Cervical
  • Upper-thoracic
  • Mid-thoracic
  • Lower-thoracic/GOJ
    • GOJ adenocarcinomas classified further by Siewert & Stein Classification

Location of Tumour

• Cervical
  • Between UOS and Sternal Notch
    • 15-20cm from incisors
  • Upper Thoracic
    • Between Sternal Notch and Azygous Vein
      • 20-25cm from incisors
  • Mid Thoracic
    • Between Azygos Vein and Inferior Pulmonary Vein
      • 25-30 cm from incisors
  • Lower Thoracic/GOJ
    • Below Inferior Pulmonary Vein

    • 30cm from incisors

  • GOJ tumours further classified by Siewert & Stein Classification (See Gastric adenocarcinoma notes)

Risk Factors/Aetiology

• SCC
  • Smokers and drinkers, oesophageal carcinogen exposure
• Adenocarcinoma
  • Fat white male with GORD

Risk Factors for Oesophageal SCC

• Smoking (RR17) and EtOH exposure (RR10) account for 90%
  • Synergistic effect
• Achalasia
• Pharyngeal pouch
• Caustic Ingestion (esp. Alkali)
• Post-Radiation (Breast Ca etc.)
• Plummer-Vinson Syndrome
• Tylosis
• Autosomal dominant condition
  • Hyperkeratosis of skin, Papillomas
• ? Achlorhydria from chronic PPI use
  • Possible low acid leads to bacteria making carcinogenic nitrosamine compounds (not proven)
• Dietary
  • Nitrosamines (fish, cured meat bacon, BBQ/pickled foods)
  • Hot food/drink
• Human papillomavirus has also been implicated

Risk Factors for Oesophageal Adenocarcinoma

• Barrett’s Oesophagus (RR = 50)
• GORD (RR = 8)
  • GORD ⇒ Metaplasia ⇒ Dysplasia ⇒ Ca
• Smoking (RR = 3.4)
• Obesity (RR = 2.4)
• Hx of Breast Ca with Rtx (RR = 4.8)
• Low SES
• H. Pylori

Clinical Presentation

• Progressive dysphagia 75%
  • Late sign, lumen usually well narrowed by this point
• Weight loss 50%
• Voice change / hoarseness
  • Very late sign
• Coughing & Aspiration
  • May be due to a tracheo-oesophageal fistula
• Fatigue
• Anaemia
• Most patients are node +ve at presentation
  • 80%; or 50% if tumor < 5cm
• May have palpable Virchow Node
  • Look for metachronous smoking-related cancer (head, neck or lung)

Pathophysiology

• NB: Often a significant submucosal extension of tumor (cranial > caudal) beyond the visible mucosal edge
• Therefore wide margins required
• 10cm proximal & 5cm distal

Pathophysiology of Oesophageal SCC

• Found Upper/Middle/Lower Oesophagus
• 1:5:2
• Invade both horizontally and vertically
• Upper tumours spread to cervical and upper mediastinal nodes
• Significant proportion also track down to perigastric nodes
• Distant mets spread to Liver, Lung, Adrenals, Kidneys

Macroscopic

• Appearance depends on depth of invasion
• 60% exophytic or fungating
• 25% ulcerative
• 15% infiltrative
• Can use lugols iodine to stain during endoscopy
  • Normal mucosa stains (glycogen content)
  • SCC doesn’t, stays white

Microscopic

• Get nests of cells with
  • Central Keratin Pearls
  • Intercellular bridges
  • Abundant eosinophilic cytoplasm
• Graded well, moderately or poorly based on
  • Extent of mitotic activity
  • Nuclear atypia
  • Degree of squamous differentiation (keratinisation)
• NB: Histology changes dramatically after neoadjuvant therapy
  • Get necrosis, inflammation, fibrosis and granulomas
• Main variants
  • Verrucous Carcinoma
    • Locally aggressive, usually large before clinical presentation
    • Well differentiated with minimal atypia
  • Spindle Cell
    • Mixed SCC and high-grade spindle cell component
    • Highly aggressive with 5 yr survival only 10-15%
  • Basaloid
    • Highly aggressive with poor prognosis

Molecular Pathology

• 80% show mutation with loss of tumour suppressor gene p53
• Also have mutations in retinoblastoma gene RB and p16

Pathophysiology of Oesophageal Adenocarcinoma

• Found in Lower Oesophagus and GOJ (80%)
• Incidence increasing heavily
  • Related to GORD and obesity
• Micro
  • Glandular structures formed by irregular columnar cells with mucus secretion
  • Typically papillary or tubular histology
• Macro
  • 50% have macroscopically infiltrative growth pattern
  • Rarely polypoid
• Graded well, moderately or poorly differentiated
  • According to glandular architecture
• 10% are mucinous/signet ring
• Up to 75% have LN involvement at diagnosis

Investigations

Clinical Assessment

• Determine symptoms and duration
• Family hx
• Medical comorbidities/fitness for surgery
• Assess nutritional status
• Pt wishes

Upper GI Endoscopy

• Main diagnostic tool
• Perform on any patient with dysphagia
• Endoscopic appearance varies, but usually seen as friable, ulcerated masses
  • Earlier tumours can appear as nodules or ulcers
• Need to document
  • Location – distance from incisors
  • Nature – friable, firm, polypoid, ulcerated (Unlikely to be T1)
  • Proximal & distal extent
  • Relationship to Cricopharyngeus, GOJ, cardia
  • Degree of obstruction
  • Describe any co-existing Barrett’s
  • Distensibility of stomach
• Do multiple biopsies, gives greater sensitivity – minimum 6-8
  • Use Lugol’s iodine for suspected SCC
• Do not dilate stenotic tumours at initial endoscopy until histology back and pt further staged
• Contrast swallow only recommended if endoscopy cannot be done for some reason

CT Chest/Abdomen

• Initial staging for
  • Nodal and distant disease
    • N – stage ~ 30-80% accuracy
  • Poor for T stage; accuracy 57%
    • Can not differentiate T1 + T2
    • T1a – nodal involvement 1-2%
    • T1b – 20%

CT PET

• Routine, but should be 2nd line after CT
  • Before EUS
    • If distant disease, then they do not need EUS
    • If suspicious local node can guide EUS location
• Best M staging tool
  • Upstages in 15%
• NB: 10% GOJ cancers not PET AVID
  • Cancers with diffuse infiltration less PET avid
• Recommended to differentiated ‘indeterminate lesions’ dx on CT
• NB: Risk of false positives or other findings that would need workup

EUS

• Better for T & N staging than CT
• Be selective
  • Early-stage disease
    • ? Deeper than T1 and would need neoadjuvant therapy
  • Suspect T4 (aortic or airway involvement)
  • Suspect nodal disease on PET
• Recommended for pts without obvious locoregional or distant disease on CT scan
  • Determine T stage and N stage accurately
  • Best T stage (accuracy 90%; sens 59-74%)
  • N staging (sens 75%; spec 85-98%, *) – increased sensitivity/specificity with EUS-FNA
• Over-stages T, under-stages N
• If finding of ascites → Cancer incurable in 75%, even with no other evidence of disease
• EUS-FNA can be useful for assessing nodal mets
• EUS changes management in up to 25% of pts + should be the test of choice for diagnosing mediastinal lymphadenopathy
• NB: May be impossible if obstructing tumour to get complete EUS

Staging Laparoscopy and Peritoneal Washings

• For patients with GOJ cancer only
  • Involvement of the intra-abdo portion
  • If finding of metastatic disease would alter management
• Do washings and send for cytology routinely
• May see occult liver disease
• Can see extent of tumour and nodes around left gastric pedicle
• Can see extent of tumour along greater curve of stomach
  • Can this still be used as a conduit?

Bronchoscopy or Endobronchial USS (EBUS)

• Consider if concerns for tracheobronchial invasion on other workup (EUS etc.)
• EBUS better than bronchoscopy
• Sensitivity 90% and spec 90% for upper/middle third Ca if tracheobronchial invasion suspected
• Presents clinically as cough
• Also useful for examining carinal/tracheal nodes
• NB: Only useful for tumours above T4/Carina

Staging

AJCC 8th Edition TNM Staging

T stage

• T1a – Into Lamina Propria/Muscularis Mucosa but not into Submucosa
  • Possible endoscopic rx
• T1b – Into Submucosa
• T2 – Into Muscularis Propria
• T3 – Into Adventitia
• T4a – Into surrounding structures that are resectable, e.g. Pleura, Pericardium, Azygos Vein, Diaphragm, Peritoneum
• T4b – Into surrounding structures that are not resectable
  • Aorta, Vertebral Body, Trachea

N stage

• N0: No regional LN mets
• N1: Mets to 1 or 2 regional LN
• N2: Mets to 3 to 6 regional LN
• N3: Mets in 7 or more regional LN

M stage M0: No distant mets M1: Distant mets

Staging System differs from SCC vs. Adenoca

• Staging Complex
  • If no neoadjuvent treatment - also depends on grade of tumour and location
  • If neoadjuvent treatment - then just TNM
• Generally:
  • Stage 1 - T1
  • Stage 2 - T2 or T3
  • Stage 3 = LN involvement or T4
  • Stage 4 = Distant mets or Significant LN involvement or T4

Pre-operative workup (for Fitness to Surgery)

• Medical Hx and clinical exam
• Bloods
  • FBC, U+E, LFTs, ABGs
• ECG
• Echo
• Pulmonary Function Tests – FEV1/FVC
• Basic exercise tolerance
  • Distance on flat, ? 2 flights of stairs
• CPET testing if borderline

Management

• All patients discussed at MDM
• HGD or T1a
  • Consider EMR if appropriate
• T1b
  • Oesophagectomy and Lymphadenectomy
• T2+
  • Neoadjuvant treatment
    • Adenocarcinoma
      • FLOT4 as per ESOPEC trial
    • SCC
      • Proximal
        • Definitive chemoradiotherapy
      • Junctional or mid
        • Young
          • Neoadjuvent CROSS Trial + surgery (Trimodal therapy)
            • Slightly better survival and local recurrence rates then definitive chemoradiotherapy
        • Old
          • Definitive chemoradiotherapy
          • Salvage surgery can be considered
          • Issue: If you give some one with a junction cancer definitive chemorads then with surgery there is a high chance of conduit necrosis as the stomach will have been in the radiation field.

Unresectable Disease

• T4b
• No plane between Aorta and Oesophagus
• Invading Trachea
• Distant mets
• Life expectancy < 12 months

Endoscopic Therapy

• Consider in high-grade dysplasia or T1 cancer
• Needs to be
  • Unifocal, and entire lesion can be removed
  • Intramucosal disease
  • Healthy oesophagus
  • Usually if can’t lift, will be T2
• At best, EMR will get complete resection (of T1a)
• At worst gives very good biopsy (for T1b)
• But no lymphadenectomy
  • NB: T1a Adenoca should have no LN involvement
  • But SCCs can have involved nodes (3.5-5.6%) due to different lymphatic drainage patterns in the Thoracic oesophagus
• Need to ablate the remaining Barrett’s (RFA, HALO)
• Complications – Bleed (1%), Perforation (0.5%), Stricture (up to 30% depending on amount excised)
• Require close ongoing surveillance, risk of metachronous Ca 20%
• T1a tumours with high risk factors (LVI, large, Poorly Differentiated) may be better served by Oesophagectomy if pt fit

Neoadjuvant Therapy

• Background
  • High morbidity and mortality with surgery
  • Positive radial margins in 20%
  • Locoregional recurrence 40-60%
  • 5Y survival poor
  • Palliative studies of radiotherapy & chemotherapy shown to have benefit
  • Neoadjuvant studies have show improved outcomes
• Benefits of neoadjuvant treatment:
  • Improved tumour oxygenation pre-op than post-op
    • Therefore more penetration of chemo/rad
  • Potential to improve resectability and reduce risk of tumour spillage
    • Increase chance of R0 resection and reduced risk of local recurrence
  • Improved chance of treating undetectable micrometastasis
  • Patient able to tolerate neoadj treatment better prior to major surgery
  • May reduce tumour volume pre-op
    • Improve dysphagia/nutrition prior to surgery
  • Spare patients with early progression from major surgery
• Disadvantages:
  • Poorly tolerated by some pts
  • May make pt physiologically less well prior to major surgery
  • May have disease progression prior to surgery
    • Though generally these patients would have done poorly anyway

Treatment paradigm

• Adenocarcinoma
  • FLOT4 as per ESOPEC trial
    • Of note prior to ESOPEC (and similar evidence prior) CROSS was the standard and prior to that MAGIC (ECF) was the standard.
• SCC
  • Proximal
    • Definitive chemoradiotherapy
  • Junctional or mid
    • Young
      • Neoadjuvent CROSS Trial + surgery (Trimodal therapy)
        • Slightly better survival and local recurrence rates then definitive chemoradiotherapy
    • Old
      • Definitive chemoradiotherapy
      • Salvage surgery can be considered
      • Issue: If you give some one with a junction cancer definitive chemorads then with surgery there is a high chance of conduit necrosis as the stomach will have been in the radiation field.

Summary of papers

• OEO2 trial
  • 2002 + updated 2009:
    • Long term follow-up shows pre-op chemo improves survival
    • 5yr survival 23% (chemo + surgery) and 17% (surgery alone)
    • Higher R0 resections and good evidence of down-staging
    • Included SCC and AC. 400 each arm
    • Chemo = Cisplatin & 5FU
  • Other studies
    • Neoadjuvant chemo increases survival: 34 → 43% at 2YS
    • Neoadjuvant chemo decreases circumferential margin positivity
  • But previous studies in potentially resectable cancer have possibly shown a non-significant survival advantage in the long term
    • e.g. RTOG 8991 = Intergroup 0113
• MAGIC Trial
  • NEJM 2006; 355:11
    • Showed survival advantage out to 5yrs for ECF
    • MAGIC trial, page 1
    • Pre & post-operative ECF and surgery, vs surgery alone (503 patients)
    • Inclusions:
      • Any age, WHO 0-1
      • Histologically confirmed adenocarcinoma
      • ≥ T2
      • Gastric or distal 1/3 oesophagus
      • No metastatic disease, resectable
    • Exclusions
      • Previous chemo/rad, poor heart/kidneys
    • Epirubicin, Cisplatin, 5FU (ECF)
      • 3 x pre-op cycles and 3 x post-op cycles
    • Surgery
      • 6/52 post chemo, then restart 6-12/52 post surgery
      • NB: Only 40% completed post-op cycles
      • Type and extent of surgery operator dependent
    • NB: 74% of study was Gastric Ca
    • Results
      • Decreased tumour size and stage
      • Significantly improved progression free and overall survival
      • 5yr survival 23% vs 36%
• CROSS Trial
  • CROSS Trial (NEJM 2012)
    • CROSS Trial, page 1
    • Neoadjuvant chemoradiation vs surgery alone
      • Carboplatin and Paclitaxel + radiotherapy 40g in 23F for 5 weeks
      • Surgery within 4-6/52 post
    • Inclusions
      • T1/N1, or T2/T3 NO or N1
      • Oesophageal and GOJ cancers (22% SCC, 75% adeno)
    • Results
      • 368 patients
      • Significantly higher R0 resection (56 vs 90%)
      • 5yr survival advantage
        • 46% vs 36%
        • Overall survival longer 48m vs 24m
        • SCC 80m vs 50m
        • Adenocarcinoma 40m and 28m
      • Results not as good for adenocarcinoma as they are for SCC
• ESOPEC, page 1
  • Methods
    • RCT - FLOT4 vs CROSS Trial
    • Inclusion: cT1 cN+, cT2–4a cN+, or cT2–4a cN0 disease
      • Excluded T1 N0, T4b
    • Primary end pointL overall survival
  • Results
    • FLOT4: 221 and CORSS 217 patients
    • OS 57% FLOT vs 50% CROSS - HR 0.7 for death
    • Progression free survival - 51% FLOT, 35% CROSS
    • Adverse event (g3 or above) 58% FLOT vs 50% CROSS
    • Mortality 3.1% FLOT vs 5.6% CROSS
  • Conclusion
    • FLOT led to improved survival

Surgery

• Indicated for T1b tumours or higher
• If < 75yrs and fit
• If possible to achieve R0 resection (T3 or less, no distant mets)
• Margins need to be large due to submucosal spread
  • Aim 10 proximal, and ideally 10cm distally
  • R0 if > 1mm clear
• Lymphadenectomy
  • Gives optimal staging and improved locoregional control
  • 2 or 3 field procedure – 2 stage done in our institution
  • Optimal no. of LN removed = 18
  • No clear differences/survival advantage for neck dissection
• Type of Operation
  • High (within 5cm of Cricopharyngeus) – Definitive chemo/rad
  • Proximal 1/3 – 3 stage
  • Middle 1/3 – Ivor Lewis Oesophagectomy
  • Distal 1/3 – Ivor Lewis Oesophagectomy
• Gastric conduit (95%)
  • Can use colon or jejunum
• Post-op jejunostomy
• Not done as a palliative operation

Lymphadenectomy Fields in Oesophagectomy

• Three-field Lymphadenectomy
  • Removal of the first and second fields along with a neck dissection clearing the Brachiocephalic, deep lateral and external Cervical nodes, as well as right and left Recurrent Nerve lymphatic chains (deep anterior cervical nodes)
• Two-field Lymphadenectomy
  • Removal of Para-aortic nodes, right and left pulmonary hilar, Paraoesophageal nodes, Subcarinal and Right Paratracheal nodes
• One-field Lymphadenectomy
  • Removal of Diaphragmatic, Right and Left paracardiac, Lesser Curvature, Left Gastric, Coeliac, Common Hepatic and Splenic Artery nodes

Route of Reconstruction

• Pre-sternal
  • Only if both other routes compromised by previous reconstructions
• Retrosternal
  • Used if emergency treatment of anastomotic dehiscence causing posterior mediastinal sepsis
• Posterior mediastinal
  • Preferred rout

Presternal Route

• Historical only
• Longest route
• 4cm longer than posterior mediastinal
• 2cm longer than retrosternal
• Only indication is if both other routes compromised by previous reconstructions

Retrosternal Route

• Potential space between sternum and anterior mediastinum developed
• 2cm longer than posterior mediastinal
• Unnatural position of cervical oesophagus in front of trachea, causes unpleasant sensation when swallowing
• Used for reconstruction when anastomotic leak causes posterior mediastinal sepsis

Posterior Mediastinal Route

• Preferred route of reconstruction in primary surgical excision of the oesophagus
• Shortest route between abdomen, apex of thorax and neck
• Gastric or colonic substitutes easily passed through posterior mediastinum after completion of mediastinal dissection in thorax
• No attempt made to close pleura

Organ of Reconstruction

• Determined by site of the primary lesion
• Should be kept as simple as possible
• Stomach
• Colon
• Jejunum

Reconstruction Using Stomach

• Best conduit if anatomy allows

• Five broad principles and practices to prepare stomach as conduit

  • Use isoperistaltic stomach maintaining vascular supply
  • Excision of the lesser curve
  • Preservation of the intramuscular vascular arcade
  • High point of the stomach
  • Gastric Drainage

• Additional methods of stomach lengthening

  • Kocher manoeuvre
  • Excision of lesser curve of stomach
  • Incision of serosa on gastric wall

• Isoperistaltic stomach maintaining vascular supply

  • Right Gastroepiploic and Right Gastric Arteries and Veins are vital to stomach viability when used as conduit
  • Greater omentum opened
    • Gastroepiploic Artery is carefully identified and preserved
  • Vascular arcade interrupted at point where right gastroepiploic meets Left
  • Short Gastrics ligated and divided

• Excision of the Lesser Curve
  • Any cancer of lower 2/3 oesophagus requires clearance of lesser curve nodes
    • +Left gastric, common hepatic, and proximal splenic A nodes
  • Left Gastric Artery should be ligated at its origin
  • Resect proximal ½ of lesser curve, including cardia
    • Preserve Right Gastric
      • Maintains intramural vascular network
  • Aim gastric conduit 5cm width or greater
    • Less risk ischaemia

• Preservation of the Intramuscular Vascular Arcade

  • Extensive intramuscular anastomoses exist between greater and lesser curves
  • Need to maintain this by not resecting too much of lesser curve
    • Maintain right gastric supply to lesser curve
  • Take care when ligating short gastrics, do away from greater curvature to avoid damage to intramural network
  • Fundus blood supply from Right Gastroepiploic Artery through this intramural arcade
    • Important as this is the region for anastomosis

• High Point of the Stomach

  • Stomach very flexible
  • High point is the logical place for anastomosis
  • Easily identified
  • Traction in upward direction after all mobilisation complete

• Gastric Drainage
  • Pyloroplasty or pyloromyotomy contentious
    • Some evidence pyloroplasty reduces incidence of gastric outlet obstruction
    • Minimal short-term complications
  • Pyloroplasty routinely done by Companion series authors
    • Reduces early life-threatening complications of:
      • Gastric stasis and aspiration
    • And late complications of
      • Vomiting and bloating
  • Heineke-Mikulicz Pyloroplasty
    • Longitudinal incision, closed horizontally

Reconstruction Using Colon

• Indications

  • Tumours needing extensive oesophageal and gastric resection
    • NB: With thorough staging, very few are actually suitable for resection
  • Previous gastric resection
  • Can consider if failed gastric conduit (necrosis) in initial attempted anastomosis

• Colon recommended over jejunum as gives larger reservoir

• Disadvantage

  • Function of the conduit deteriorates over time
  • Not as durable as stomach in the long term

• Aim to use isoperistaltic segment depending on individual variations in vascular anatomy

  • Transverse Colon based on Left Colic vessels
    • Cannot perform if Marginal Artery not sufficient at Splenic Flexure
  • Right Colon based on Middle Colic vessels

• Technical Considerations

  • Colonoscopy and CT-Angio prior
  • Pre-op mechanical bowel prep and PO antibiotic cover to sterilise bowel for 48hrs pre-op
  • Free omentum from hepatic flexure, transverse, splenic flexure
  • Mobilise entire colon to deliver outside, to inspect blood supply
  • Sigmoid mobilisation gives length to tunnel transverse to chest
  • Divide proximal colon, make anastomosis to oesophagus, then get rid of redundancy by anchoring sutures to hiatus
  • Re-establish continuity of colon (end-to-end anastomosis)
  • Perform colo-jejunostomy or colo-gastrostomy with the conduit

Reconstruction Using Jejunum

• Third choice after stomach and colon

• Can do

  • Roux-en-Y
  • Segmental interposition
  • Free jejunal transfer with microvascular anastomosis
    • If high in the neck

• Anastomotic Principles

  • Adequate blood supply
  • Tension free
  • Epithelial to epithelial approximation
  • Precise layer to layer sutures
  • No difference in single/double layer
  • No difference in sutures/staples
  • ? wrap with transposed omentum

See Oesophagectomy

Complications of Surgery

• 60% get complications
  • Clavien-Dindo ≥ 3 17%
  • 30-day mortality 2%
  • 90-day mortality 4.5%
• Immediate
  • Intra-op
    • Bleeding
    • Injury to other structuresàRLN, Phrenic N, thoracic duct, L)MB etc
    • Anaesthetic complications
• Early
  • Pulmonary complications
    • Aspiration
    • Pneumonia
  • CV complications
    • AF (Common)
    • MI
  • Chylothorax (5%)
  • Anastomotic leak (2-5%)
    • Conduit already relatively ischaemic, and if in the neck then may be under a
  • degree of tension o Conduit Ischaemia
  • DVT/PE
• Late
  • Functional Conduit Disorders
    • Dysphagia (65%, 3-5% severe) – Need to consider stricture
    • Reflux (60-80% depending on how diagnosed)
    • Delayed emptying (50%, vagotomy)
    • Dumping (up to 50% , improves with time)
    • GOO
  • Hernia
    • Ventral
    • Thorax
    • Diaphragmatic

Long Term Issues

• GORD 60%
• Diarrhoea 50%
• Bloating 45%
• Dysphagia 40%
• Dumping Syndrome 15%

Anastomotic Leak and Leak from Gastric Conduit

• Early leak (48-72hours)
  • Technical fault
  • If condition of patient good – reoperate to correct fault
• Late leak (5-10 days)
  • Usually due to conduit ischaemia or tension on anastomotic line
  • If leak at the oesophagogastric join
    • Operating at this time is hazardous and often detrimental
    • Use intensive non-operative management
      • NG decompression
      • Radiologically guided percutaneous drains – chest and mediastinum
      • Antibiotics
      • Jejunostomy feeding
      • Don’t stent
    • Late anastomotic leakage does not result in high mortality
  • If leak at Gastric resection line dehiscence
    • Need to re-operate as large amounts of leakage
  • Anastomotic leak, cervical oesophagogastrostomy ≈ 20%
    • Can drain

Conduit Necrosis

• Can be catastrophic complication
• Must diagnose early with endoscopy
• Resuscitate
• IV abx
• Return to theatre
  • Exclude with cervical oesophagostomy
  • Close viable gastric remnant
  • Place feeding jejunostomy (if haven’t already)
• Once stable – colonic interposition

Chylothorax

• Transthoracic 2-3%, trans-hiatal up to 10%
• Apparent by day 7
  • Increase in chest fluid after commencement of diet
• Results in massive malnutrition, immunosuppression and reduction in CD4 count due to loss of WCC/fat nutrition
• Chyle = intestinal lymphatic fluid enriched with fat
  • Confirm by measuring TAG concentration of drain output
• Low output leak < 500ml/day
  • Treat with enteral feed with medium chain fatty acids or TPN
    • Thoracic duct should transport 4L/day
• Large leak
  • Should be managed with return to OT and ligation of thoracic duct
• Prophylactic abx with Cotrimoxazole (covers pneumocystis)

RLN Palsy

• At risk during cervical oesophagectomy or high anastomosis
• Usually only unilateral – usually contralateral nerve can compensate
• Unilateral RLN injury
  • Varying degrees of hoarseness
  • Microaspiration
  • Coughing
  • Other symptoms seriously affecting patients’ quality of life
• Bilateral RLN injuries
  • May induce aphonia
  • Dyspnoea
  • Asphyxia
  • Can be life threatening

Gastric Outlet Obstruction

• Prevented by routine pyloroplasty
• Always bring entire stomach conduit into chest
• Prevents changes of pressure across stomach
• Low dose erythromycin or metoclopramide can reduce effects

Other Complications

• Dumping Syndrome
  • Relatively common but most resolves in 12 months
  • Manage by avoidance of high carb loads
• Duodeno-gastro-oesophageal reflux
  • Common, can be acid or alkaline reflux
  • Control with motility agents and PPI
  • Symptoms can be troublesome
  • More common for thoracic anastomosis than cervical
• Benign anastomotic stricture
  • Common
  • Usually respond to single dilation

Adjuvant Therapy

Adjuvant Treatment

• Chemotherapy
  • Low quality of evidence - each patient should be discussed at an MDT
  • In patients who have had neoadjuvent treatment
    • Residual pathological disease
      • Approach undefined
      • Can consider with different chemotherapy regime
    • No residual pathological disease
      • Not recommended
  • If patient has not had neoadjuvent treatment
    • SCC
      • Not indicated after R0 resection of SCC
        • Irrespective of nodal status
    • Adenocarcinoma
      • Treatment can be considered in > T2 / N+
• ChemoRTx:
  • ? some survival advantage in patient who have not had neoadjuvent treatment
    • based on Intergroup 0116 Trial:
      • Inclusion - primaries ≥ T3 and/or node-positive, gastric / GOJ
      • Med survival 27 vs 36 months
        • But this study has been criticized, as only 40% of pts had a R0 resection
• Radiotherapy alone
  • not recommended in one RCT
  • If radiotherapy given; 60-64Gy total - 5 days a week for 7 weeks
• Immune checkpoint inhibitors
  • Indicated for patients with residual disease (not funded currently in NZ)
  • Nivolumab
    • CheckMate 577 trial
      • 794 patients who had received neoadjuvant CRT for esophageal or EGJ cancer (70 percent AC)
      • Nivolumab (240 mg) or placebo every 2 weeks for 16 weeks followed by nivolumab 480 mg or placebo every 4 weeks
      • Primary end point
        • median disease-free survival- (22.4 versus 11 months) across all groups

Radical Chemoradiotherapy

• Consider if
  • Very proximal tumour (cervical)
  • Locally advanced (unable to get R0 resection)
  • Patient not fit for resection
  • SCC
• Chemoradiotherapy vs surgery alone:
  • Survival rates are similar (German study & FFCD 9120 trial)
    • But there are no major RCTs so Rx has to be tailored
  • If no surgery, get increased local recurrence
  • If surgery, get increased early (post-op) mortality
  • 2yr survival 35-39% no different (but DFS better in surgery group)
• ChemoRTx vs Surgery + ChemoRTx for advanced SCC: (FFCD 9102 trial)
  • No diff
  • Advanced disease should only be treated with CRT
• ChemoRTx vs RTx alone in SCC:
  • ChemoRTx better
  • Median survival 14 vs 9 months
  • 5yr survival 27% vs 0

Management of Mets, Palliation, Recurrence

• Indications for palliation:
  • Patient choice/comorbid
  • Clinical/radiological distant metastatic disease
  • T4 with invasion into airway/aorta (T4b)
  • Peritoneal disease on laparoscopy
• Options depend upon previous treatment
  • If patient had surgery previously
    • → Chemoradiation
• If patient had no previous surgery
  • → Consider palliative surgery, if operable
  • Palliative options = “Best supportive care”

Endoscopic Options

Self-Expanding Metal Stents (SEMS)

• Partially covered best (uncovered gets ingrowth, fully covered migrates)
• 3cm longer than tumour, prox + distal flange
• Deployed by endoscopy under fluoroscopic guidance
• Indications:
  • Recurrence following chemoradiotherapy
  • Contraindications to chemoradiotherapy
  • Actual or impending fistula
    • If Tracheo-oesophageal fistula – use covered SEMS
  • Total dysphagia, incl. pts who are candidates for multimodal therapy
• Contraindications:
  • Curable by multimodal therapy (unless total dysphagia)
  • Stent placement < 2cm from UES
  • Complete luminal occlusion
  • Multiple multi-angulated lesions
  • Inability to tolerate, high ECOG, or significant bleeding tendency/anticoags

Laser/Photodynamic Therapy

• Relieves dysphagia in up to 70%
• Rare as time consuming and requires multiple sessions.
• Indications:
  • Ingrowth of stents
  • Cervical oesophagus lesions that cannot be stented
• Duration of dysphagia free usually 4-16 weeks
• Pulses of energy that cause tissue necrosis and vaporization – tissue damage only occurs for 0.5mm beyond treatment site so rare to cause perforation
• Complications:
  • Early:
    • Chest pain (mucosal burn)
    • Perforation – 5%
    • Haemorrhage 1%
• Late:
  • Tumour regrowth – usually require monthly tx
  • Delayed strictures
  • Persistent dysphagia

Argon Plasma Coagulation

• Argon emitted as a jet of gas that then has high-freq electrical energy passed through it to ionize gas into ‘plasma’ which distributes a superficial ‘burn’ to tissues
• As tissue dries out and desiccates it becomes less conductive therefore limiting risk of perforation

Intra-Tumour 100% EtOH injection

• Consider if bleeding tumour etc.
• 0.5ml-1ml aliquots – can use as much as needed.
• Irregular tissue necrosis can occur
• Often need repeated treatments

Palliative Radiotherapy

• Successful in relieving dysphagia in ≈ 50% of patients
• SCC much more radiosensitive
• External beam
  • 30-60Gy over 5-6 weeks
  • Complications:
    • Pulmonary fibrosis
    • Stricture
    • Fistula
    • Recurrent dysphagia (only 40% pts have acceptable dysphagia)
• Brachytherapy (? Available in NZ)
  • Brachytherapy applicator passed over the guidewire and positioned at the tumour by fluoroscopy.
  • Pt the moved to a protected treatment room and connected to the ‘Selectron’ machine – transfers caesium-137 micropellets
  • Usually given as a single dose of 10-15Gy
  • RCT found this to have better effect for dysphagia with less morbidity
• NB: Initial response is for tumour to swell = Dysphagia initially worsens
  • May heal with a stricture

Palliative Chemotherapy

• Improves survival from 9 → 12mths
• Cisplatin + 5-FU + Paclitaxel
• Response rates 20-50%
• Cisplatin, 5-FU, paclitaxel & anthracycline → promising response (Cochrane 2006)
• NJ or PEG
  • ? Appropriateness of feeding in terminal cancer

Prognosis/Natural History

Main determinants:

• Depth of invasion
• Presence of LN mets (these correlate)
• Non-resectable Ca → 8-month average survival
• Post-op ≈ 5% mortality; morbidity 30-40%
• Post-op 5yr Survival ≈ 15-20%
• For SCC:
  • 5YS after surgery =10-20%
  • 35% if neoadjuvant Rx is given
• NB: Similar survival if SCC treated with chemoradiotherapy only

Follow-up

• Unit specific protocols
• ? 6/12 for 2yrs then annually
• May look at doing closer if radical chemo/rad used
  • Could potentially benefit from earlier salvage surgery
• Most of discussion is about functional status and reflux symptoms
  • Long term PPIs
• CT based on symptoms
  • Weight loss etc.
• No evidence for routine scans
• No evidence that early diagnosis of stage 4 helps
• Follow-up routine endoscopy also contentious

Rarer Forms of Oesophageal Malignancy

• Account for approx. 2%
• Neuroendocrine
  • Most common, usually distal, poor prognosis
• Carcinosarcomas
  • ? Two separate tumors that have collided,
  • Polypoid, lower 2/3
• Melanomas
  • Lower 2/3, look for satellite lesions, poor prognosis
• Sarcomas
  • Kaposi’s leiomyosarcomas
  • Equal distribution along oesophagus