Transcript Gastric Cancer - St. Luke's

Gastric Cancer:
Current Concepts
David Shin
Dept of Surgery Grand Rounds
August 24, 2005
Epidemiology
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Gastric cancer was the fourth most common
cancer in the world in 2004, and is expected to
remain fourth in 2005.
Worldwide there are 930,000 new cases and
700,000 deaths per year. Sixty percent of new
cases occur in developing countries.
There is tremendous geographic variation, with
the highest death rates in Chile, the former
Soviet Union, China, and Japan.
Epidemiology
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In the United States gastric cancer is the 15th
most common cancer, with 21,860 new cases
expected this year, and 11,550 deaths.
The incidence of gastric cancer has declined
significantly worldwide in the last century, with a
marked decline in the US since the 1930s.
Epidemiology
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In New York State there were an average of
1955 cases annually between 1998-2002, with
1070 deaths.
Male to female ratio of 2:1 in the US; 3:2 in
New York.
Median age at diagnosis is 65 years (40-70).
Incidence increases with age, peaking in the 7th
decade.
Risk Factors
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Diet
Low fat or protein consumption
 Salted meat or fish
 High nitrate consumption
 High complex carbohydrate consumption
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Risk Factors
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Environment
Poor food preparation (smoked/salted)
 Lack of refridgeration
 Poor drinking water (well water)
 Smoking
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Risk Factors
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Social
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Low social class (except in Japan)
Medical
Prior gastric surgery
 H. pylori infection
 Gastric atrophy and gastritis
 Adenomatous polyps
 Male gender
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Risk Factors
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Helicobacter pylori
Presence of IgG to H. pylori in a given population
correlates with local incidence and mortality from
gastric cancer.
 Different strains elicit different antibody responses.
The cagA strain causes more mucosal inflammation
and thus a higher risk of gastric cancer than cagAnegative strains.
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Risk Factors
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Adenomatous polyps
10-20% risk of developing cancer, especially in
lesions greater than 2 cm.
 Multiple lesions increase the risk of developing
cancer.
 Presence of polyps increase the chance of
developing cancer in the remainder of mucosa.
 Endoscopic surveillance is required after removal of
polyps.
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Decreasing Incidence
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Improved nutrition and refrigeration of foods
Lower incidences of H. pylori due to increased
antibiotic use and cleaner water/sanitation leading to
decreased transmission of disease
Earlier detection and treatment in certain countries
Anatomy
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Most of the blood supply to the stomach is
from the celiac artery.
Four main arteries:
Left and right gastric along the lesser curvature
 Left and right gastroepiploic along the greater
curvature.
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Blood supply to the proximal stomach also
comes from the inferior phrenic and short
gastric arteries
Anatomy
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Occasionally (15-20%) an aberrant left hepatic
artery arises from the left gastric – a concern if
the left gastric needs to be divided.
The extensive anastomotic connections between
these arteries allow, in most cases, three of the
four vessels to be ligated as long as the arcades
between the curvatures are not disturbed.
Anatomy
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Venous drainage parallels the arterial supply
Left and right gastric veins drain into the portal vein
 Right gastroepiploic drains into the SMV
 Left gastroepiploic drains into the splenic vein
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Anatomy
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Lymphatic drainage is into four zones:
Superior gastric
 Suprapyloric
 Pancreaticolienal
 Inferior gastric/subpyloric
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All four drain into the celiac group of nodes and
into the thoracic duct.
Gastric cancers drain into any of these groups
regardless of location of the tumor.
Anatomy
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Innervation:
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Parasympathetic via the vagus.
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Left anterior and right posterior.
Sympathetic via the celiac plexus.
Anatomy
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Stomach has five layers:
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Mucosa
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Epithelium, lamina propria, and muscularis mucosae*
Submucosa
 Smooth muscle layer
 Subserosa
 Serosa
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Clinical Presentation
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Symptoms are often absent in early stages, and
when present are often ignored, missed, or
mistaken for another disease process.
Vague discomfort and/or indigestion
 Epigastric pain that is constant, non-radiating, and
unrelieved by food ingestion.
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Proximal tumors may present with dysphagia.
Antral tumors may present with outlet
obstruction.
Clinical Presentation
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Diffuse mural disease may present with early
satiety due to decreased distensibility.
Up to 15% of patients develop hematemesis and
40% are anemic at presentation.
Clinical Presentation
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Unfortunately most patients present in later
stages of disease, with evidence of metastatic or
locally advanced tumor.
Palpable abdominal mass, ovarian mass,
supraclavicular or periumbilical lymph nodes.
 Obstruction from tumor invasion into transverse
colon.
 Hepatomegaly, jaundice, ascites, and cachexia.
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Diagnosis
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Endoscopy is the diagnostic method of choice.
With multiple biopsies (seven or more) the
diagnostic accuracy approaches 98%.
 Cytologic brushings can also be obtained.
 Size, morphology, and location of tumor can be
documented, as well as any other mucosal
abnormalities.
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Endoscopy
Endoscopy
Diagnosis
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Double contrast barium
swallow has 90%
accuracy and is cost
effective.
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No ability to distinguish
between malignant and
benign ulcers.
Diagnosis
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Endoscopic Ultrasound (EUS) is a newer
modality that is being used in some center to
help stage the tumor.
Extent of wall invasion and lymph node
involvement can be assessed.
Overall accuracy is 75%.
Poor for T2 tumors (38%)
 Better for T1 (80%) and T3 (90%)
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Remains operator dependent.
Preoperative Workup
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Once diagnosis of gastric cancer has been made,
CT scan is useful for evaluation of any distant
disease.
Limited in detecting early primary and small (<5mm)
metastatic tumors.
 Accuracy of lymph node staging ranges from 25 to
86%.
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If CT scan is negative, then laparoscopy is
recommended as the next step in evaluation.
Preoperative Workup
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Laparoscopy detected metastatic disease in 23 to
37% of patients deemed eligible for curative
resection by CT scan.
Laparoscopy improves palliation in these
patients by avoiding unnecessary laparotomy in
about one fourth of patients presumed to have
local disease on CT scan.
AJCC Cancer Staging Manual, Sixth Edition
Stomach
(Lymphomas, sarcomas, and carcinoid tumors are not included.)
AJCC Cancer Staging Manual, Sixth Edition
Stomach
(Lymphomas, sarcomas, and carcinoid tumors are not included.)
AJCC Cancer Staging Manual, Sixth Edition
Stomach
(Lymphomas, sarcomas, and carcinoid tumors are not included.)
Treatment
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Surgical resection remains the mainstay of treatment
and is the only curative option.
More recently pre- and post-chemoradiation therapy
has been scrutinized to see if there is any benefit to
survival.
The issue of extent of resection appears to have been
settled. As long as adequate tumor margins are
achieved, subtotal gastrectomy has the same survival as
total, with decreased morbidity.
Neoadjuvant Therapy
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Radiation alone
1970’s in Russia 152 patients were randomly assigned
to surgery alone or preop radiation with 20 Gy a
week prior to surgery. Five year survival rates were
30% and 39% respectively.
 In 1998 a Chinese group reported a prospective
series of 370 patients who underwent surgery only
or had 40 Gy preop radiation. Five year survival was
19.8% vs 30.1% with radiation. Resectability and
radical resection rates were also improved.
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Neoadjuvant Therapy
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Radiation alone
In both studies reported perioperative mortality and
anastamotic leak rates were not significantly
different.
 Further studies in radiation alone were largely
abandoned in favor of studies including
chemotherapy.
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Neoadjuvant Therapy
Neoadjuvant Therapy
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Chemotherapy alone
A randomized Netherlands study (DGCT) was
unable to show any difference with preop
chemotherapy. This may be in part due to the
regimen used – FAMTX (FU, doxyrubicin,
methotrexate).
 In the U.K. the MAGIC trial using ECF (epirubicin,
cisplatin, FU) has shown promising preliminary
results, with 10% more resectable cases and
improved disease-free survival.
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Neoadjuvant Therapy
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Combined chemoradiation therapy
Has shown a beneficial impact on surgical outcomes
in esophageal and rectal cancers, making it an
attractive approach for gastric cancer as well.
 The M.D. Anderson Cancer Center reported several
studies, one in 2004 where patients who underwent
preop chemoradiotherapy – FU, leucovorin,
cisplatin, and 45 Gy in 25 fractions over 5 weeks –
achieved pathological complete and partial response
in 64% of all operated patients.
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Neoadjuvant Therapy
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Chemoradiation therapy
These patients showed a significantly longer median
survival of 64 months in comparison to 13 months
in patients who did not reach complete or partial
response.
 Further clinical trials are warranted to further show
any benefit of neoadjuvant chemoradiation.
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Surgical Treatment
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Aggressive resection of gastric cancer is justified in the
absence of distant metastatic spread.
The surgery is tailored mainly to the location of the
tumor and known pattern of spread.
R0 resection should be achieved, with a minimum of
6cm margins from gross tumor.
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R0 – tumor free margins
R1 – microscopic disease
R2 – gross tumor at margins
Minimum of 15 nodes should be removed.
Surgical Treatment
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Tumors in the cardia and proximal stomach
account for 35-50% of gastric adenocarcinomas.
For these tumors a total gastrectomy should be
performed, as opposed to proximal gastric
resection which is associated with higher
morbidity and mortality rates.
Distal tumors may be removed by distal
gastrectomy as long as adequate margins are
achieved.
Surgical Treatment
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The extent of lymphadenectomy remains controversial.
The JGCA classifies the lymph node basins into 16
basins, and are grouped according to the location of
the primary tumor as either D1, D2, or D3 nodes. In
general:
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D1 – removal of group 1 nodes along the lesser and greater
curvature.
D2 – D1 plus group 2 nodes along the left gastric, common
hepatic, celiac, and splenic arteries.
D3 – D2 plus para-aortic and distal lymph nodes
Lymph Node Stations
Surgical Treatment
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A 1993 survey by the ACS showed a 77.1% resection
rate in 18,365 patients, with a postoperative mortality
rate of 7.2% and 5-year survival rate of 19%. Of these
only 4.7% were D2 dissections.
In comparison, the Japanese routinely perform D2
dissections, with 5-year survival rates above 50%.
Although earlier detection accounts for much of the
survival benefit, when comparing cancers in the same
stage, the Japanese continue to have improved survival.
Survival Outcomes
120
100
80
US
Japan
60
40
20
0
Stage I
Stage II
Stage III
Stage IV
Surgical Treatment
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Based on this and other retrospective data, four
randomized studies comparing D1 to D2
dissections have been conducted.
All four trials, including two large ones from the
Netherlands and Britain all show the same data;
that D2 dissection significantly increases
morbidity and mortality without any significant
increase in survival.
Surgical Treatment
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Splenectomy and pancreatectomy were found to
be important risk factors for morbidity and
mortality after D2 dissection.
In the DGCT trial a subgroup analysis of
patients who underwent D2 without
splenectomy and/or pancreatectomy had a
significantly improved survival benefit.
A randomized British trial also supported these
findings in stage II and III disease.
Surgical Treatment
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Based on these findings, many groups are
recommending “over-D1” lymphadenectomy
for gastric cancers in Western society.
The large difference between the Japanese
results and Western results remains largely an
enigma.
Surgical Treatment
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Choice of reanastamosis depends on extent of
resection.
Very distal gastrectomies may be reanastamosed
via a Billroth I, II, or Roux-en-Y.
Subtotal gastrectomies will require a Billroth II
or Roux-en-Y.
Total gastrectomies are best served with a Rouxen-Y anastamosis.
Surgical Treatment
Surgical Treatment
Surgical Treatment
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In the U.S. 20 to 30% of patients present with
stage IV disease.
Palliative treatment should be geared toward
relief of symptoms with minimal morbidity,
usually non-operative.
Laser recanulization and endoscopic dilatation
with or without stent placement has shown
success in relieving outlet obstruction.
Adjuvant Therapy
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A 1999 review of the National Cancer Database
reported that only 29% of patients undergoing
gastrectomy for cancer had some form of
adjuvant therapy.
This shows the lack of convincing data up to
that point that adjuvant therapy increase survival
in gastric cancer.
Adjuvant Therapy
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In 2001 the Southwest Oncology Group trial
was published, showing for the first time in a
large prospective randomized trial a survival
benefit for patients undergoing gastrectomy for
cancer.
Median survival was 27 months in the surgery
only group, and 36 months after
chemoradiotherapy.
Adjuvant Therapy
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Survival was improved only in the D0 and D1
groups.
Details on late toxicity have yet to be followed
up on and reported.
Radiation toxicity had been improved with the
use of IMRT (intensity modulated RT),
especially renal toxicity.
Adjuvant Therapy
Outcomes
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What can you expect?
Patients who have undergone a potentially
curative resection have an average 5-year survival
of 24 to 57%.
More useful survival rates are stratified by stage
of disease.
Outcomes
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Recurrence rates remain high, from 40 to 80%
depending on the series being quoted.
Locoregional failure rate 38 to 45%, with most
recurrence in the gastric remnant at the
anastamosis, gastric bed, and lymph nodes.
Surveillance is important. Patients should be
followed every 4 months for the first year, then
6 months for 2 more years. Yearly endoscopy
should be performed for subtotal gastrectomies.
Choice of Operation
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Open gastrectomy with lymph node dissection –
at least D1 – is the current operative standard.
Laparoscopic gastrectomy has been shown to be
safe with similar survival for patients with distal
cancer.
Learning curve needs to be overcome, which
may be difficult with the decreasing number of
gastric cancer cases in the U.S.
End