2. Esophageal Cancer J. Timothy Sherwood MD Thoracic Surgeon
Virginia Cardiovascular and Thoracic Surgery
Mary Washington Hospital
Fredericksburg, VA
Assistant Professor of Surgery
The Johns Hopkins School of Medicine
Baltimore, MD

3. Esophageal Cancer

4. EPIDEMIOLOGY OF ESOPHAGEAL CARCINOMA
USA - 5 cases per 100,000
Iran, China, Russia cases per 100,000
Risk factors for squamous cell cancer
Geography, age, sex, race (> black men), smoking
(5-10 times)
Alcohol, dietary and nutritional factors
Risk factors for adenocarcinoma
Increased incidence in last years (> white male)
Barrett’s esophagus (50%)

6. PROFILE OF ESOPHAGEAL CANCER IN THE UNITED STATES
Represents approximately 1% of all cancers
Annual incidence of 4 per 100,000 population
Estimated 12,300 new cases in 1998
Estimated 11,900 deaths in 1998
Male-to-female ratio of 3-4:1
Median age is 67 (adenocarcinoma occurs most often in fourth decade of life)
Death rate among African-Americans is 3 times that of whites
Squamous cell carcinoma mainly affects African-Americans
95% of patients with adenocarcinoma are young white males

7. BARRETT’S ESOPHAGUS AND ESOPHAGEAL CANCER
Precise definition difficult
Incidence of cancer in Barrett’s mucosa is increasing
Risk of cancer times normal
Dysplasia precedes malignancy
Low grade dysplasia often remains stable or regresses
High grade dysplasia is equivalent to carcinoma in situ
High grade dysplasia predicts imminent or existing cancer (50%)
75% of resected cancers are associated with adjacent high grade dysplasia
Endoscopic surveillances detects cancer early and improves survival

8. Barrett’s Esophagus Columnar epithelium replaces squamous
“Specialized intestinal metaplasia”
White males
Increased incidence of adenocarcinoma
Long segment vs short segment

10. Natural History of Dysplasia
Low-grade dysplasia
<50% interobserver agreement
10-28% incidence of HGD or Adenoca in 5 years
High-grade dysplasia
85% path agreement
Study:
76 pts; 5 yr follow-up
59% incidence of adenocarcinoma
100 pts; 8 yr f/u
32% incidence of adenocarcinoma
1/3 of patients have invasive cancer at esophagectomy
Variable progression of dysplasia
Studies:
48 pts w/ LGD
10% progressed to high-grade dysplasia, 1 patient w/ adenoca at 41 months
43 pts w/ LGD
12% progressed to adenoca in 60 months

11. Risk of Adenocarcinoma
Barrett’s patients:
6 prospective studies
Mean annual incidence: 1%
30-fold higher risk than general population

12. Treatment of Barrett’s
Treatment of associated GERD
Endoscopic surveillance to detect dysplasia
Treatment of dysplasia

13. Treatment of High-Grade Dysplasia
Esophagectomy
Endoscopic ablative therapy
YAG Laser
Photodynamic therapy
Endoscopic mucosal resection
Chemoprevention
NSAIDS
COX2 inhibitors
Meta-analysis- 9 studies: 43% decrease in ca
Intensive surveillance

14. PRECANCEROUS CONDITIONS OF THE ESOPHAGUS
Barrett’s Esophagus
Lye Stricture
Tylosis
Plummer-Vinson Syndrome
Celiac Sprue
Zenker’s Diverticulum
Achalasia
Chagas Disease

15. RISK FACTORS Cultural patterns Tobacco use
Alcohol consumption (particularly whiskey)
Diet
High-nitrosamine foods
Vitamin-deficient diets (particularly vitamins C and E deficient)
Micronutrient deficiency (eg, niacin, magnesium, molybdenum, zinc and riboflavin)
Scalding beverages
Head and neck cancers
Obesity (3 fold higher risk)

16. RADIOGRAPHIC EVALUATION OF ESOPHAGEAL CANCER
Barium swallow and endoscopy are complimentary in early detection
CT pathologic correlation shows a sensitivity and specificity of 50%, with an overall accuracy 40-70%
CT is useful in the detection of distant metastasis
CT is useful as surveillance tool postoperatively
MRI does not have a defined role
Laparoscopy and PET scanning

17. Diagnosis of Esophageal Cancer
Esophagus- Malignant
Esophageal Cancer
Squamous Cell Ca
Mid-esophagus
Adenocarcinoma
Distal Esophagus

18. Endoscopy Fungating mass at distal esophagus

19. ENDOSONOGRAPHY IN ESOPHAGEAL CARCINOMA
Most noteworthy advance in gastrointestinal endoscopy during this decade
Provides detailed images of the esophageal wall and adjacent structures utilizing ultrasound technology
Ideally suited for staging esophageal cancer
Better than CT in assessing depth of tumor infiltration (T stage) and regional lymphadenopathy

20. Endoscopic Ultrasound
Gives detailed anatomic information on local tumor involvement T
Depth of penetration N
Lymph node involvement

21. PET Scanning for Esophageal Cancer Staging
Evolving
Probably Standard of Care
Use for extraregional staging
Not lymph nodes
Changes Management in 5% to 30%

22. TNM STAGE GROUPING AND STANDARD TREATMENT
STAGE STANDARD TREATMENT
Stage Tis N M Surgery, ?radiation, chemoradiation; ?hematoporphyrins
Stage T N M Surgery or Chemoradiation
Stage IIA T N M Surgery or
T3 N M Chemoradiation
Stage IIB T1 N M Surgery or
T N M Chemoradiation
Stage III T N M0 Chemoradiation
T Any N M0 Surgery for T3 tumors
Stage IV Any T Any N M1 Radiation therapy  intraluminal intubation and dilation  chemotherapy
Stage IVA Any T Any N M1a
Stage IVB Any T Any N M1b

23. Surgical Resection

24. SURGICAL TREATMENT OF ESOPHAGEAL CANCER
Extent of esophageal resection
Extent of dissection
Conduit alternatives
Stomach, colon, jejunum
Surgical approaches
Right thoracic (Ivor-Lewis), right thoracotomy-abdominal-cervical
Left thoracotomy, left thoracoabdominal, left thoracoabdominal cervical
Transhiatal esophagectomy
Trans-sternal
Video assisted esophagectomy

25. STANDARD SURGICAL APPROACHES FOR ESOPHAGECTOMY
Technique Procedures Comments
Transthoracic Laparotomy: preparation of gastric conduit; Near-total thoracic esophagectomy
(Ivor Lewis) lymph node dissection One of the two most common
Right thoracotomy to mobilize and resect techniques in North America
esophagus
Intra thoracic anastomosis
Transhiatal Laparotomy: preparation of gastric conduit; Less radical than en block. Best lymph node dissection for tumors below inferior
Left neck exploration; mobilization of pulmonary ligament, especially at
esophagus gastroesophageal junction
Transhiatal resection One of the two most common
Cervical anastomosis techniques in North America

26. Esophagogastrostomy “Gastric Pullup”
Mobilization of Stomach
Lengthening of the stomach
Drainage of the stomach
Transpositioning of the stomach
Anastomosis

27. Mobilization of stomach and drainage procedure
Gastric Pullup
Mobilization of stomach and drainage procedure

28. Gastric Pullup
Creation of gastric tube for
esophageal replacement

29. I prefer THE
Avoids painful thoracic incision
Anastomosis done easier in neck
If leak, neck leak easier to manage than thoracic
OR time 4 hours

30. Transhiatal Esophagectomy
Transhiatal Esophagectomy “THE”
Denk 1913
Turner 1933
Antethoracic tunnel
Ong 1960
First pharyngogastric anastomosis
Kirk 1974
Thomas 1977
Orringer 1974
stages
Abdominal stage
Left cervical incision
anastomosis

31. Transposition of Stomach
I prefer THE
Avoids painful thoracic incision
Anastomosis done easier in neck
If leak, neck leak easier to manage than thoracic
OR time 4 hours

32. Gastric Pullup Cervical Anastomosis

33. Ivor Lewis Right Thoracotomy

34. SURVIVAL BY DISEASE STAGE
Stage 5-Year Survival Rate (%)
0 (Tis, N0, M0) >90
1 (T1, N0, M0) >50-80
IIA (T2 or T3, N0, M0)
IIB (T1 or T2, N1, M0)
III (T3, N1, M0 or T4, any N, M0) <10-20
IV (any T, any N, M1) Rare

35. NEOADJUVANT THERAPY OF ESOPHAGEAL CARCINOMA
Rationale
Reducing bulk and downstaging tumor
Eradicating tumor in lymph nodes
Reducing tumor dissemination during surgery
Prevention of chemo resistant clones
Assessment of tumor responsiveness
Delivery prior to surgical disruption of blood supply

36. NEOADJUVANT THERAPY OF ESOPHAGEAL CARCINOMA
Preoperative RT (randomized trial)
Can reduce tumor bulk, render some specimens sterile, does not increase postoperative mortality or morbidity, resection rate or long-term survival
Preoperative chemoradiation therapy
Complete responders with documented pathologic remission have better survival (5 yr - 40%)
Operability and resectability rates high
Randomized trials ongoing

38. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer.
Memorial Sloan-Kettering Cancer Center
J Clin Oncol Aug 20;25(24):
216 patients received preoperative chemotherapy,
227 underwent immediate surgery
no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group

39. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in esophageal carcinoma: a meta-analysis
The Lancet Oncology - Volume 8, Issue 3 (March 2007)
Ten randomized comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1209) and eight of neoadjuvant chemotherapy versus surgery alone (n=1724) in patients with local operable esophageal carcinoma were identified
A significant survival benefit was evident for preoperative chemoradiotherapy…….The findings provide an evidence-based framework for the use of neoadjuvant treatment in management decisions.

40. American Joint Committee on Cancer staging system does not accurately predict survival in patients receiving multimodality therapy for esophageal adenocarcinoma
J Clin Oncol Feb 10;25(5):
Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
The current AJCC staging system is not a good predictor of survival after CRT. Although patients with a pCR do have improved long-term survival relative to patients with residual disease, this method places too much emphasis on residual depth of invasion and fails to identify patients with residual disease who have good long-term survival.
Recursive partitioning analysis more accurately identifies nodal disease and metastatic disease as the most important prognostic variables. Degree of treatment response is less prognostic than nodal involvement.

41. Proposed Revision of the Esophageal Cancer Staging System to Accommodate Pathologic Response (pP) Following Preoperative Chemoradiation (CRT)
The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Annals of Surgery. Volume 241(5), May 2005, pp
Our analyses demonstrate that following CRT, pTNM continues to predict survival. The extent of pathologic response following CRT is an independent risk factor for survival (pP) and should be incorporated in the pTNM esophageal cancer staging system to better predict patient outcome in esophageal cancer

42. Esophageal Cancer Increasing Incidence Presents at later stage
Overall poor survival, but improving
Increasing evidence for neoadjuvant therapy / Surgery improving outcomes