Transcript Carcinoma of the Esophagus

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
Esophageal Cancer
EPIDEMIOLOGY OF
ESOPHAGEAL CARCINOMA
 USA -
5 cases per 100,000
 Iran, China, Russia - 500 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
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 Risk
factors for adenocarcinoma
Increased incidence in last 10-15 years (> white male)
 Barrett’s esophagus (50%)
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PROFILE OF ESOPHAGEAL
CANCER IN THE UNITED STATES
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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
BARRETT’S ESOPHAGUS AND
ESOPHAGEAL CANCER
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Precise definition difficult
Incidence of cancer in Barrett’s mucosa is increasing
Risk of cancer 50-100 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
Barrett’s Esophagus
 Columnar
epithelium
replaces
squamous
 “Specialized
intestinal
metaplasia”
 White males
 Increased
incidence of
adenocarcinoma
 Long segment vs
short segment
Natural History of
Dysplasia
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Low-grade dysplasia
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<50% interobserver agreement
10-28% incidence of HGD or Adenoca in 5 years
High-grade dysplasia
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85% path agreement
Study:
– 76 pts; 5 yr follow-up
• 59% incidence of adenocarcinoma
– 100 pts; 8 yr f/u
• 32% incidence of adenocarcinoma
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1/3 of patients have invasive cancer at esophagectomy
Variable progression of dysplasia
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Studies:
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48 pts w/ LGD
– 10% progressed to high-grade dysplasia, 1 patient w/ adenoca at
41 months
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43 pts w/ LGD
– 12% progressed to adenoca in 60 months
Risk of Adenocarcinoma
 Barrett’s
6
patients:
prospective studies
 Mean
annual incidence: 1%
 30-fold
higher risk than general
population
Treatment of Barrett’s
 Treatment
of associated GERD
 Endoscopic
surveillance to detect
dysplasia
 Treatment
of dysplasia
Treatment of High-Grade
Dysplasia
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Esophagectomy
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Endoscopic ablative therapy
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YAG Laser
Photodynamic therapy
Endoscopic mucosal resection
Chemoprevention
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NSAIDS
– COX2 inhibitors
– Meta-analysis- 9 studies: 43% decrease in ca
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Intensive surveillance
PRECANCEROUS CONDITIONS OF
THE ESOPHAGUS
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Barrett’s Esophagus
Lye Stricture
Tylosis
Plummer-Vinson Syndrome
Celiac Sprue
Zenker’s Diverticulum
Achalasia
Chagas Disease
RISK FACTORS
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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)
RADIOGRAPHIC EVALUATION
OF ESOPHAGEAL CANCER
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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
Diagnosis of Esophageal
Cancer
 EsophagusMalignant
Esophageal
Cancer
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Squamous Cell
Ca
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Mid-esophagus
Adenocarcinoma
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Distal Esophagus
Endoscopy
Fungating mass at distal
esophagus
ENDOSONOGRAPHY IN
ESOPHAGEAL CARCINOMA
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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
Endoscopic Ultrasound
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Gives detailed
anatomic information
on local tumor
involvement
T
 Depth of
penetration
N
 Lymph node
involvement
PET Scanning for
Esophageal Cancer Staging
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Evolving
Probably Standard
of Care
Use for extraregional
staging
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Not lymph nodes
Changes
Management in 5%
to 30%
TNM STAGE GROUPING AND
STANDARD TREATMENT
STAGE
Stage 0
Stage 1
Stage IIA
Tis
N0
Stage IV
T1
T2
T3
T1
T2
T3
T4
Any T
Stage IVA
Stage IVB
Any T Any N M1a
Any T Any N M1b
Stage IIB
Stage III
N0
N0
N0
N1
N1
N1
Any N
Any N
M0
M0
M0
M0
M0
M0
M0
M0
M1
STANDARD TREATMENT
Surgery, ?radiation, chemoradiation;
?hematoporphyrins
Surgery or Chemoradiation
Surgery or
Chemoradiation
Surgery or
Chemoradiation
Chemoradiation
Surgery for T3 tumors
Radiation therapy  intraluminal
intubation and dilation  chemotherapy
Surgical Resection
SURGICAL TREATMENT OF
ESOPHAGEAL CANCER
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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
STANDARD SURGICAL APPROACHES
FOR ESOPHAGECTOMY
Technique
Procedures
Comments
Transthoracic
(Ivor Lewis)
Laparotomy: preparation of gastric conduit;
lymph node dissection
Right thoracotomy to mobilize and resect
esophagus
Intra thoracic anastomosis
Near-total thoracic esophagectomy
One of the two most common
techniques in North America
Transhiatal
Laparotomy: preparation of gastric conduit;
lymph node dissection
Left neck exploration; mobilization of
esophagus
Transhiatal resection
Cervical anastomosis
Less radical than en block. Best
for tumors below inferior
pulmonary ligament, especially at
gastroesophageal junction
One of the two most common
techniques in North America
Esophagogastrostomy
“Gastric Pullup”
 Mobilization
of Stomach
 Lengthening of the stomach
 Drainage of the stomach
 Transpositioning of the stomach
 Anastomosis
Gastric Pullup
Mobilization of stomach and
drainage procedure
Gastric Pullup
Creation of gastric tube for
esophageal replacement
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Transhiatal
Esophagectomy
Transhiatal
Esophagectomy “THE”
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Denk 1913
Turner 1933
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Ong 1960
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Antethoracic tunnel
First pharyngogastric
anastomosis
Kirk 1974
Thomas 1977
Orringer 1974
stages
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Abdominal stage
Left cervical incision
– anastomosis
Transposition of Stomach
Gastric Pullup
Cervical Anastomosis
Ivor Lewis
Right Thoracotomy
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)
15-30
IIB (T1 or T2, N1, M0)
10-30
III (T3, N1, M0 or T4, any N, M0)
IV (any T, any N, M1)
<10-20
Rare
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
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NEOADJUVANT THERAPY OF
ESOPHAGEAL CARCINOMA
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Preoperative RT (randomized trial)
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Can reduce tumor bulk, render some specimens
sterile, does not increase postoperative mortality or
morbidity, resection rate or long-term survival
Preoperative chemoradiation therapy
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Complete responders with documented pathologic
remission have better survival (5 yr - 40%)
Operability and resectability rates high
Randomized trials ongoing
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.
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Memorial Sloan-Kettering Cancer Center
J Clin Oncol. 2007 Aug 20;25(24):3719-25.
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
Survival benefits from neoadjuvant
chemoradiotherapy or chemotherapy
in esophageal carcinoma: a metaanalysis
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The Lancet Oncology - Volume 8, Issue 3 (March 2007)
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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
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A significant survival benefit was evident for preoperative
chemoradiotherapy…….The findings provide an evidencebased framework for the use of neoadjuvant treatment in
management decisions.
American Joint Committee on Cancer staging
system does not accurately predict survival in
patients receiving multimodality therapy for
esophageal adenocarcinoma
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J Clin Oncol. 2007 Feb 10;25(5):507-12.
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Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
[email protected]
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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.
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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.
Proposed Revision of the Esophageal Cancer
Staging System to Accommodate Pathologic
Response (pP) Following Preoperative
Chemoradiation (CRT)
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The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Annals of Surgery. Volume 241(5), May 2005, pp 810-820
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
Esophageal Cancer
 Increasing
Incidence
 Presents at later stage
 Overall poor survival, but improving
 Increasing evidence for
neoadjuvant therapy / Surgery
improving outcomes