Esophageal Cancer

1. 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.

2. 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

3. 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

4. Esophageal CA -- find distant mets • Distant mets • Bronchoscopy in proximal and middle third esophageal CA’s • eval. for posterior tracheal invasion • “slight compression” still resectable • “abnormal tracheal mucosa” unresectable

5. 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

6. Esophageal CA -- eval. lymph nodes • Lymph node status • Laparascopic staging • Laparscopic ultrasound of liver not useful

7. 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

8. 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 peri-gastric => no need to resect these • Invasion of muscularis propria --> 80% LN involvement

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

10. Esophagectomy -- Types of operations • Incision strategies: • Ivor-Lewis • Laparotomy, thoracotomy • Transhiatal • Conduit strategies: • Gastric pull-up • Colonic interposition • Jejunal interposition

11. 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

12. Esophagectomy -- Types of operations • Anastomosis strategies: • Technique: • Stapled (EEA) • Ease • Strictures • Sutured • single layer vs double layer, running vs interrupted

13. 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

14. 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

15. Esophagectomy -- Intra-operative complications • Recurrent laryngeal nerve injury • especially in cervical dissections

16. Esophagectomy -- Operation by stage • Barrett’s 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

17. Esophagectomy -- Operation by stage • Barrett’s 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

18. 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

19. 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”)

20. 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

21. 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

22. 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)

23. 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

24. 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

25. 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

26. 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

27. 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)

28. 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

29. 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

30. 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

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

32. 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

33. Esophageal CA -- chemoradiation • Pre-op chemoradiation (cisplatin/5-FU) • Increases surgical M/M by 5-15% • With high does rad’n (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

34. 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

35. 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)

36. 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

37. 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

38. 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 -- can’t detect regional nodes well • Histologic response -- not avail. without resection • Future: biologic serum markers ?