Oesophageal Cancer
DEFINITION
Oesophageal Ca
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EPIDEMIOLOGY

Incidence
Increasing due to GORD / Barrett's and obesity
 
Age
Later decades

Geographical distribution
SCC in East, AdenoCa in West

Risk factors - SCC
Personal
Tobacco, alcohol, caustic injury
Environmental
Poor socioeconomic status
Smoked foods, hot drinks
Predisposing conditions
Achalasia
Past head & neck cancer
Plummer Vinson syndrome
Thoracic irradiation
Tylosis A

Risk factors - AdenoCa
Personal
Reflux, Barrett's, Obesity, Tobacco
Predisposing conditions
Meds lowering LES tone
Thoracic irradiation.
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AETIOLOGY

90% - AdenoCa or SCC
- others GIST, carcinoid, melanoma etc = rare

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BIOLOGICAL BEHAVIOUR

Pathophysiology
Aggressive
SCC tend to invade locally and involve airway / other adjacent structures.
- usually diagnosed late
- LN spread is typically around the regional mediastinal nodes and cervical LN.
AdenoCa typically is distal; related to metaplasia.
- as for SCC, 2/3 have locoregional LN spread at diagnosis
- tends to be lower mediastinum and upper abdomen, including coeliacs.

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MANIFESTATIONS

Symptoms

Local
Usually dysphagia (50-75%)
Odynophagia 20%
Systemic
Weight loss (50-60% at dx)
Metastatic
Dyspnoea, hoarseness, back pain

Rest on surveillance.
Signs
If advanced disease:
- cachexia, effusions, hepatomegaly, Virchow's node
D E A B M I M

INVESTIGATIONS

Endoscopy
Best diagnostic tool, biopsy.

Staging
CT chest/abdo/pelvis
PET
- routinely recommended by Cameron authors
--> determines resectability.
EUS
- if CT/PET ok for spread
--> depth of invasion and regional LN involvement; very accurate 80% for TN
- (EMR can provide even better staging for pts with early cancer in Barrett's)
Laparoscopy / thoracoscopy
- in rare cases when suspect lesions remain that are not confirmed.

TNM (AJCC)
Tx
T0
Tis = high-grade dysplasia
T1a = lamina propria
T1b = submucosa
T2 = muscularis propria
T3 = Adventitia
T4a = Invades adjacent structures eg pleura, pericardium, diaphragm, but resectable
T4b = Invades structures eg aorta, vertebrae, trachea (unresectable)

N0
N1 = 1-2
N2 = 3-6
N3 = 7+

M0
M1

G1 = well differentiated
G2 = moderately
G3 = poorly
G4 = undifferentiated

Location
Upper (20-25cm from incisors)
Mid (25-30)
Low (30-40)
GOJ

Grade
0 = Tis
I = T1N0M0
IIA = T2N0M0
IIB = T3N0M0 or T1/2N1M0
IIIA = T1/2N2M0, T3N1M0, T4aN0M0
IIIB = T3N2M0
IIIC = T4aN1-2M0, T4bNanyM0, TanyN3M0
IV = TanyNanyM1 
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MANAGEMENT

MDT
Yes.
Increased morbidity from oncology Rx

Early
I.e. in context of Barret's
- they are more likely to have in-situ or mucosal cancer than early invasive cancer (only ~10%).
Therefore, more conservative approaches suitable.
T1aN0M0 --> EMR, dual treatment with ablation for any remaining columnar mucosa.
T1bN0M0 --> conventional esophagectomy
- if invading submucosa LN risk >30%, hence esophagectomy; if T1N0M0 but limited to lamina propria, then LN Risk <5%, hence EMR
- vagal-sparing oesophagectomy is an option.

Regionally-Advanced Disease
T2-4aN0-3
Surgery alone pretty dismal; multi-modal therapy now favoured.
Key Points
1. No diff between pre-op radiotherapy and surgery or surgery alone
--> hence no role for pre-op radiation in any pt with indication for surgery.  Both are locoregional therapies.
2. Small benefit for neoadjuvant chemotherapy
- aim is elimination of micromets, downstaging, recurrence reduction, improved resectability
- and can often better tolerate the chemo before surgery (complications mean they may not get it at all)
--> RCTs somewhat variable but overall likely modest survival benefit of 3months+ with more at 5 yr follow-up.
3. Possible benefit for neoadjuvant tri-therapy (chemorad then surgery)
--> better survival, but see pt 1; radioRx not better in itself; may be chemo effect. 
4. No evidence for adjuvant radio
- no improved survival and harm from side effects
5. Response to chemo predicts outcome
--> complete response = >50% better survival at 5 yrs
6. Adjuvant chemo regionally advanced disease (T3+Nany)
--> probably should have post op chemo if have not had pre-op, but no good evidence for survival benefit
--> there is good evidence for post-op chemorad, but nasty to go through.
7. The lack of clear benefit from any modality has led to questions about the benefit from surgery at all (e.g. vs radioRx)
--> unresolved; but becoming more common practice for SCCs

Bottom line
Neo-adjuvant chemo = yes, survival benefit.
Americans also give rad = nasty but reasonable.
Adjuvant = unclear role.

Advanced Disease
T4b or T3/4a with Many nodes (>6)
--> bimodal chemoradio Rx most suitable. Very poor survival.

Surgical Considerations

Principles
R0 resection
Remove lymph nodes for long term survival
Recover normal diet

Keys to success
Meticulous patient selection
Experienced team of intensivists and nurses
Careful technique with meticulous preparation of the conduit, thorough LN dissection and attention to detail.

Incisions - options
Transthoracic (TTE)
- Ivor-Lewis when distal GOJ tumour
- or "three-hole" McKeown modification for high tumours
Transhiatal (THE)
- left cervical incision and blunt dissection of esophagus with cervical anastomosis
Minimally-invasive oesophagectomy (MIE)
- right thoracoscopic mobilization
- lap mobilization of stomach and intrathoracic or cervical anastomosis
- can do laparoscopic THE

Advantages / Disadvantages
TTE and MIE allow direct vision
- less bleeding, complete soft tissue dissection,
- more complete LN excision
However, TTE = higher morbidity
- if intrathoracic anastomosis, can get devastating mediastinitis
THE avoids thoracic morbidity
- and if leaks, can simply open cervical wound at bedside.
- but blunt dissection of oesophagus can lead to inadequate LN excision and understaging.
- and increased risk of injury to azygous, other intrathoracic structures with poor vision.
Meta-analysis of RCTs has shown:
- 8 LNs more in THE than TTE
- Longer length of stay in TTE
- No difference in survival at 5 yrs, but TTE tended to be performed on more advanced Ca, so ?biased evidence.
- Significant heterogeneity.
--> At present, either is fine, case by case basis appropriate
MIE
- significant learning curve, increased complications in first 30-50 procedures.
- safe in high-volume centers and appears to have equivalent outcomes with open
--> by LN retrieval and survival.

Conduit / Reconstruction
Regardless of approach, gastric conduit preferred for reconstruction
Preserve the right gastroepiploic artery
Colon or jejenum if stomach unusable.

Nodal Dissection
2 goals, as always: local control and staging.
- appropriate goal for staging unclear, but perhaps 15-30.
The lymphatic drainage is extensive and complex... (Cameron 10th p51)
- no single pattern or spread
--> hence SLN has no role
--> hence need for extensive lymphadenectomy.
80% of T2 tumours will have +ve LNs
- does extended lymphadenectomy confer greater survival?
- THE can include a lymphadenectomy, but only with blunt dissection.
- TTE/MIE can achieve formal 2 (thoracic / abdominal) 3 (+cervical) field.
20-40% of mid or distals have involved cervical nodes.
- should cervical resection be routine?
--> no difference in RCT, only in weaker studies
- note the usual problem of more LNs means better staging so stage-migration may explain the survival observations.
--> bottom line is that there is no evidence for extended lymphadenectomy in oesophageal cancer.

Extent of Soft Tissue Resection?
En-bloc esophagectomy aims to include a buffer zone of soft tissue in continuity with oesophagus
- avoids violating tissue planes.
- includes azygous vein, thoracic duct, a rim of diaphragm.
Currently no evidence for this extensive en-bloc resection.

Other Controversies
Pyloroplasty or pyloromyotomy?
In general, this is supported by the literature
- allows emptying, does not lead to more dumping or reflux.
Feeding jejunostomy?
In general, not supported by the literature.
- nasojejunal or TPN feeding is adequate in peri-op period
- but does allow optimal nutrition if post-op complications
- and helps prevent overgrowth and translocation
- permits nutritional supplementation if required
--> and most of these factors have not been considered in studies
--> can defend either doing it or not

Post-operative Management
High-dependency of ICU setting
Restrictive approach to fluids is usually appropriate
- esp. to help prevent pulmonary complications.
J-feeding on day 1 and slowly progress to goal rate as tolerated.
NG tube that traverses the anastomosis is kept for 3-5d
- i.e. until return of bowel function
No evidence for routine evaluation of anastomosis w Ba swallow
- advance diet as tolerated after NG withdrawn
Workup for anastomic leak:
- CXR, Ba swallow, chest CT
---> if fever, leukocytosis, on or after d3, or SVT, or confusion / sepsis / confusion / hypotension / tachy / desats.

Follow-up / Surveillance
Recurrence:
- us. within 2 yrs, median time 8.5m
- most with recurrence do not survive 2-3y
--> hence, early intensive follow up is reasonable.
Early disease
EMR, Tis or T1 disease - EGD 3monthly
Esophagectomy
History and exam every 3 months, for 2y, then annually.
- CT chest abdo every 6m for 2y,  then annually for 5y
- no known advantage for routine blood work
- EGD if dysphagia to ascertain stricture vs cancer
Surveillance EGD q2y for Barrett in the remnant or new cancer.

Metastatic Disease
50% at diagnosis.
Chemorad
- response is 15-50%
Dismal survival at 1y
Stents and dilations have removed the indications for palliative surgery.

Stents
Palliative
Self expanding metal stents have revolutionised minimally invasive care, with a low perforation rate.
Low profile delivery; can be inserted at endoscopy.
+/- under fluoroscopy
Uncovered, partially covered or completely covered varieties
- stainless steel or nitinol
- mostly covered are used; prevent ingrowth (outweighs higher risk of migration)
--> e.g. Polyflex stent
When stent coils embed into mucosa / submucosa, they induce an inflammatory reaction, helps prevent migration.
Flared ends that remain bare, for luminal anchorage.
Variey of sizes, 10 most common, can get longer.
Increased internal diameter helps with normal diet.
Technique:
GA
Identify ends of stricture, radio-opaque markers.
Guidewire through stricture, gentle dilation if reqd.
Delivery system over guidewire.
Grasping forceps if reqd, reposition stent.
Problems
GORD if placed over GEJ
Migration if not anchored distally,
GEJ angulation may increase ulceration complication or worse
Cervical oesophagus are less well tolerated; globus, migration, aspiration risk.

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REFERENCES
Cameron 10th