Esophageal Cancer

Approx. 13,000 cases/year in USA

Post-esophagectomy overall 5 yr survival = 18% At presentation, 57% patients are Stage 3, with a 10% post-esophagectomy surv. At presentation, 24% patients are Stage 2, with a 35% post-esophagectomy surv. At presentation, patients who are Stage 1, have an 80% post-esophagectomy surv.

Esophageal CA -- pre-op staging

TNM staging somewhat overbroad
If T1, but tumor is in mucosa only:
Lymph node metastases < 10%

If T1, but tumor extends into submucosa:

Lymph node metastases = approx. 30

Distant mets, lymph nodes, wall penetration

Esophageal CA -- find distant mets

Distant mets
CT chest and abdomen -- mostly useful in trying to detect distant mets but, CT chest and abdomen -- only 60% accurate in detecting regional lymph node disease but, CT chest and abdomen -- underestimates tumor stage in 40% of patients Addition of PET may improve accuracy

Esophageal CA -- find distant mets

Distant mets
Bronchoscopy in proximal and middle third esophageal CAs
eval. for posterior tracheal invasion
slight compression still resectable abnormal tracheal mucosa unresectable

Esophageal CA -- eval. lymph nodes

Lymph node status
Thoracoscopic staging can find LNs, but poorly predicts unresectability Laparoscopic staging can change treatment in 30% of distal esophageal Cas
Matted celiac nodes Carcinomatosis Small liver lesions

Esophageal CA -- eval. lymph nodes

Lymph node status
Laparascopic staging
Laparscopic ultrasound of liver not useful

Esophageal CA -- pre-op staging

Wall penetration
Endoscopic ultrasound -- incorrect in determining wall depth 15-20% of the time Endoscopic ultrasound -- incorrect in determining nodal status 25 - 30% of the time Endoscopic ultrasound -- less accurate after neoadjuvant therapy

Esophageal CA -- pre-op staging

Wall penetration
High grade dysplasia = 43% occult adeno CA Tumor limited to submucosa --> 19% LN involvement
3% had more than 4 nodes Nodes limited to peri-esophageal, not spleen or perigastric => no need to resect these

Invasion of muscularis propria --> 80% LN involvement

Esophageal CA -- chemoradiation
Treatment of choice for Stage 4 (mets)
Stent esophageal lesion, chemo and radiation
SCC responds to radiation better than Adeno CA

Esophagectomy -- Types of operations

Incision strategies:
Ivor-Lewis
Laparotomy, thoracotomy

Transhiatal

Conduit strategies:
Gastric pull-up Colonic interposition Jejunal interposition

Esophagectomy -- Types of operations

Anastomosis strategies:
Location:
Cervical Intrathoracic
Anastomotic technique does not affect leak rate Radiation, vascular supply does

Post-op feeding strategies:

Jejunosotmy feeding tube placed at time of esophagectomy

Esophagectomy -- Types of operations

Anastomosis strategies:
Technique:
Stapled (EEA)
Ease Strictures

Sutured
single layer vs double layer, running vs interrupted

Esophagectomy -- Types of operations

Anastomosis strategies:
Tension issues
Tacking sutures not often used in stapled anastomoses

Gastric emptying strategies

15% pyloric obstruction rate Pyloroplasty, pyloromyotomy ?
+/- Graham patch

Vagotomy

Esophagectomy -- Intra-operative complications

Bleeding
average < 800 cc for Ivor-Lewis transhiatal esophagectomy bleeding
left thoracoabdominal extension vs. left thoractomy Aortic a., bronchial a., azygous v. bleeding --> pack, then upper sternal split

Tracheobronchial injury
secure airway by advancing ETT, then repair
primarily vs. pedicled flap buttress

Esophagectomy -- Intra-operative complications

Recurrent laryngeal nerve injury

especially in cervical dissections

Esophagectomy -- Operation by stage

Barretts esophagus with High-grade dysplasia or intramucosal adeno-CA
No visible tumor on endoscopic U/S
but again, U/S may not be accurate in distinguishing mucosal vs. submucosal confinement

Vagal sparing esophagectomy, transhiatal esophagectomy

If no regional disease detected

Esophagectomy -- Operation by stage

Barretts esophagus with High-grade dysplasia or intramucosal adeno-CA
No visible tumor on endoscopic U/S
but again, U/S may not be accurate in distinguishing mucosal vs. submucosal confinement

Investigational: Mucosal ablation (laser, photodynamic), endoscopic mucosal resection

Esophagectomy -- Operation by Stage

Tumor confined to submucosa on U/S
Visible tumor on endoscopic U/S
75% have tumor past mucosa into submucosa and beyond when seen on U/S 56% have lymph node metastases (both limited to and extending past submucosa)

Extended transhiatal esophagectomy Complete lower mediastinal and upper abdominal lymph node resection
since only 19% had LNs if limited to submucosa not en bloc since only 3% had > 4 LNs

Esophagectomy -- Operation by Stage

Tumor into or through muscularis propria
75% to 85% LN involvement 45% have > 4 LNs 30 - 40% have distant LNs involved (25% celiac LNs)

radical en bloc esophagectomy (DeMeester)

1-5 % local recurrence rate

however, most surgeons do not perform radical en bloc resections, relying on adjuvant therapy
35% local recurrence operation alone (i.e. not en bloc)

Esophagectomy -- Operation by Stage

Radical en bloc esophagectomy (DeMeester)
1-5 % local recurrence rate
Compare 35% local recurrence overall after esophagectomy

Five-year survival for Stage 3 is 23 - 50%

Compare overall five-year Stage 3 post-esophagectomy survival rate of 10%

Cervical lymph node dissection

Mid-thoracic tumors and upper third tumors have 45% cervical lymph node mets

Esophagectomy -- Operation by Stage

Cervical lymph node dissection
Mid-thoracic tumors and upper third tumors have 45% cervical lymph node mets No survival advantage to cervical LN resection (Nishimaki, 1999)
Exception was 1 to 4 LNs (but how can you tell in advance?)

Significant additonal morbidity (80%) with additional lymph node (three-field) dissection

Esophagectomy -- Complications
Mortality 3 - 5%, Morbidity 15-18% Anastomotic leaks -- 1 - 5%
Cervical
leak rate 0-12%, post-op day 5-10 fever, crepitance, drainage, erythema, leukocytosis requires wide incision and drainage, not repair 1/3 develop stricture --> I&D (not repair)

Esophagectomy -- Complications
Thoracic --> Gastrograffin swallow vs. CT
With-hold feeding additional 5-7 days if < 1 cm contained leak
Repeat esophagogram

Exploration if free leak or > 1 cm contained leak (risk of erosion by mass effect) Pediatric endoscope at exploration time (?) Assess for large disruptions or necrosis of conduit

Esophagectomy -- Complications
Conduit necrosis or large disruptions
Resect anastomosis, debride edges End cervical diverting esophagostomy Gastric remnant returned to abdomen Drainage Reconstruction in several months

Esophagectomy -- Complications
Conduit obstruction at diaphragm
Two fingers width alongside conduit at diaphragm Resect head of left clavicle, first rib, manubrium in cervical anastomoses as needed

Diaphragmatic bowel herniation

Prevent by suturing conduit to hiatus with 3 - 4 sutures Vague lower thoracic/upper abd. cramping pains CXR; CT or contrast study if in doubt Repair with hiatal closure and anchoring sutures

Esophagectomy -- Complications
Chylothorax
1 - 3% Ligate intraoperatively when identified Massive (800 cc/day) chest tube output at 5 - 7 days post-op vs. tension chylothorax if no Chest Tube Feed cream -- note change in chest tube character Stop enteral feeds; start TPN Explore promptly and ligate thoracic duct through right thoracotomy, VATS, or prior thoracotomy

Esophagectomy -- Complications
Anastomotic strictures -- 5 - 42%
More often if lye, leak, small EEA staplers, suture technique, irradiation Requires dilatation (80% dilatation success)
Early after leak Combined with endoscopy Use 46 Fr or larger Maloney dilators, balloons when necessary Repeat until 6 months of stability use extra care if colon, small bowel conduit

Chronic (> 12 mo) cervical anastomotic strictures

Stricturoplasty / SCM flap (50% failure) / Lat. Dorsi flap / free radial arm flap / pectoralis myocutaneous flap (like ENT flaps)

Esophagectomy -- Complications
Delayed hemorrhage (rare)
Consider splenic injury

Aspiration pneumonia -- 3%
Videoesophagogram before re-feeding 5-7 days

Dysphagia Regurgitation Delayed emptying

Only 15% develop pyloric obstruction Balloon dilatation, erythromycin, metoclopramide

Dumping

Esophagectomy -- Post-op diet

Smaller, more frequent meals Drink liquids after meals to avoid gastric distension Avoid high carbohydrate diets Liberal anti-diarrheal use
Dumping symptoms usually resolve in 6 - 12 months

Esophageal CA -- radiation
20 to 40 Gy over 2 - 4 weeks (1.75 to 3.75 Gy/fx) Squamous cell carcinoma -- more radiosensitive Preoperative radiation versus surgery alone no improved survival in long-term randomized trials Post-op radiation versus surgery alone no improved survival, but higher stricture rate improved local recurrence rates in node negative mid- to upper-third SCCs

Esophageal CA -- chemo
Pre-operative chemo (Cisplatin, 5-FU)
Only 19% response No change in survival No change in local recurrence rates or patterns

Esophageal CA -- chemoradiation
Pre-op chemoradiation (cisplatin/5-FU)
40% (histologic) response rate (average)
Similar response rates for SCC and AdenoCA Response rate dependent on time to surgery following chemoradiation What is ideal delay to surgery?
In rectal CA, 6-8 week gap allows more restorative surgery than does a 2 week gap Allow healing ability to recover Allow clinical tumor shrinkage

Esophageal CA -- chemoradiation
Pre-op chemoradiation (cisplatin/5-FU)
Increases surgical M/M by 5-15%
With high does radn (high dose (3.5 Gy) /fraction (TE fistula) Anastomotic leaks, strictures Toxicities
myelotoxicity if Mitomycin C, etoposide, vinblastine added

Average results, not controlled by delay to surgery

Esophageal CA -- chemoradiation
Pre-op chemoradiation (cisplatin/5-FU)
Non-significant improvements yet seen
Urba(2001, AdenoCA only) : 3 year survival 16% -> 30% (P=0.15)
Local recurrence 41% --> 19%

Clark(2000abstract) : 2 year 35% --> 45% (P=.002)

median survival difference 4 months, short F/U

Walsh (1996, adenoCA only) : highly controversial: 6% --> 32% Bossett(1997, Stage 1 and 2 SCC only): no difference

Esophageal CA -- chemoradiation
Pre-op chemoradiation (cisplatin/5-FU)
Survival differences may be lost by 5 years Benefits not yet substantiated by long-term studies (2002 review)

Esophageal CA -- chemoradiation alone

Chemoradiation instead of surgery
Studies show pathologic and clinical response rates comparable to historical esophagectomy survivals in Stage 2 and 3 carcinomas
EORTC trial in progress -- 30 Gy with 5 FU/Cisplatin

Comparisons are not against en bloc resections

Esophageal CA -- chemoradiation alone

Chemoradiation (CRT) instead of surgery
40-60% of CRT alone die with local recurrence/failure Compare 9% with CRT plus surgery

Surgical salvage following CRT alone

no difference in salvage versus CRT alone

Esophageal CA -- chemoradiation alone

Chemoradiation instead of surgery
Current methods to determine complete (clinical) response are inadequate to predict which patients might not require surgery in addition to chemoradiation
Endoscopic U/S or MRI -- accuracy inadequate in determining local and regional tumor PET, CT -- cant detect regional nodes well Histologic response -- not avail. without resection Future: biologic serum markers ?