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LOCATION MATTERS: LIGAMENTS
AND LYMPHATIC PATHWAYS IN
STAGING OF GASTRIC
ADENOCARCINOMA
Jennifer J. Young, MD, MPH 1, Anokh Pahwa, MD2,
Maitraya Patel, MD1,2, Matilda Jude, MD2,
Monica Deshmukh, MD2, Michael Nguyen, MD2,
Shaden F. Mohammad, MD2
1UCLA
Department of Radiological Sciences, David Geffen School of
Medicine
2Olive
View-UCLA Medical Center, Department of Radiology
No relevant financial disclosures
EDUCATIONAL GOALS AND TARGET AUDIENCE
1. Review gastric anatomy
2. Identify spread of disease via perigastric ligaments
3. Describe pathways of lymphatic involvement
4. Correlate imaging of gastric adenocarcinoma with the new
American Joint Committee on Cancer (AJCC) staging system
and summarize prognostic and management implications
• Target audience: practicing Radiologists, Gastroenterologists,
Residents and Fellows in training.
BACKGROUND INFORMATION
• More than 988,000 cases of gastric cancer annually worldwide. 5 th most
common cause of cancer-related mortality in Western populations.
• Adenocarcinoma is the most common histology of gastric cancer in the
United States, comprising >90% of new diagnoses.
• 65% of patients in the US present at an advanced stage (T3/T4) with nearly
85% of those accompanied by lymph node metastasis.
• CT and endoscopic ultrasound (EUS) are important tools in the preoperative
evaluation, with complete staging achieved at the time of surgery.
• Local, extra-gastric regional and distant involvement have clinical
implications in patient management and prognosis.
• It is vital for the Radiologist to be aware of the new American Joint
Committee on Cancer (AJCC) TNM (tumor, node, metastasis) staging system
for gastric cancer, to accurately stage the disease and help guide patient
management.
GASTRIC ANATOMY
Image courtesy of Lisa Nishiyama and Christina Ma, MD
EMBRYOLOGY OF THE STOMACH AND
Embryologic development of peritoneal
LIGAMENTS
organs and ligaments
•
The stomach is derived from the primitive foregut
and is suspended by the:
FL
Liver
GHL
Stomach
• Ventral mesogastrium- attaches the foregut
to the anterior abdominal wall and forms:
GSL
Pancreas SRL
• Falciform ligament (FL)
Spleen
• Gastrohepatic ligament (GHL)
• Hepatoduodenal ligament (HDL)
• Dorsal mesogastrium- connects the foregut
to the posterior abdominal wall and forms:
Adult position of peritoneal organs and
ligaments
FL
• Gastrocolic ligament (GCL)
• Gastrosplenic ligament (GSL)
• Splenorenal ligament (SRL)
Liver
GHL
Stomach
GSL
Pancreas SRL
Spleen
EMBRYOLOGY OF THE STOMACH AND
PERIGASTRIC LIGAMENTS
The gastrohepatic and hepatoduodenal ligaments
are continuous and form the lesser omentum and
the anterior border of the lesser sac. The
hepatoduodenal ligament contains the portal triad.
Sagittal view shows the gastrocolic ligament,
greater omentum and transverse mesocolon.
Stomach
Liver
Pancreas
GCL
GHL
HDL
Transverse
mesocolon
Stomach
Transverse colon
Greater
omentum
PERIGASTRIC LIGAMENTS
Ligament
Course
Gastrohepatic ligament Left hepatic lobe to lesser
curvature of stomach
Associated vasculature
Left gastric artery and vein
Hepatoduodenal
ligament
Hepatic hilum to the lesser Hepatic artery, portal vein,
curvature of the stomach extrahepatic bile ducts
Gastrocolic ligament
Greater curvature of the
stomach to transverse
colon
Right and left
gastroepiploic arteries
Greater omentum
Fatty apron from the
transverse colon covering
the small bowel
Epiploic arteries and
branches of the
gastroepiploic arteries
Gastrosplenic ligament
Fundus and proximal body Short gastric and left
of stomach to splenic
gastroepiploic arteries
hilum
Splenorenal ligament
Spleen to tail of pancreas
Distal splenic artery and
proximal splenic vein
PERIGASTRIC LIGAMENTS ON CT
Perigastric ligaments contain blood vessels (arteries, veins, lymphatics), lymph nodes, and nerves
Gastrohepatic ligament
A
Hepatoduodenal ligament
B
Gastrocolic ligament Greater omentum
D
C
Hepatoduodenal ligament
Gastrosplenic ligament
E
Splenorenal ligament
F
F
Axial, coronal and sagittal CECT demonstrates the location of the: (A) gastrohepatic ligament with the left gastric artery as anatomic
landmark (green arrow), (B) hepatoduodenal ligament with portal vein and hepatic artery as anatomic landmarks (blue arrow), (C)
gastrocolic ligament containing gastroepiploic vessels (yellow arrow) (D) greater omentum extending from the transverse colon and
covering the small bowel (pink arrows). (E) gastrosplenic ligament containing left gastroepiploic arteries (purple arrow) and (F)
splenorenal ligament containing distal splenic artery and proximal splenic vein (orange arrow).
PRE-OPERATIVE STAGING
Gastric cancer spreads through the
following mechanisms:
•
1. Regional: directly to contiguous
organs or through perigastric ligaments.
•
2. Distant: lymphatic, hematogenous, or
peritoneal
Patients are staged using a combination of:
•
Endoscopic evaluation with endoscopic
ultrasound (EUS)
•
CT of the chest, abdomen, and pelvis
•
If results are equivocal for distant
disease:
• Staging laparoscopy
• PET-CT - not helpful for
locoregional disease, but detects
metastatic disease
AMERICAN JOINT COMMITTEE ON
CANCER (AJCC): Gastric Cancer TNM
Staging System
• 7th edition released in 2009
• TNM staging system goals:
• Delineating anatomic markers for
categorizing esophageal versus
proximal gastric cancers
• Consistency in staging with other
GI tract malignancies
• Worldwide applicability for gastric
cancer cases in Asian countries
and Western countries
7TH AJCC GASTRIC CANCER STAGING SYSTEM
UPDATE TO TUMOR LOCATION
•
Cancers with the tumor epicenter within the
proximal 5 cm of the stomach that DO cross
the esophagogastric (EG) junction are now
staged using esophageal cancer system.
•
Cancers with the tumor epicenter within the
proximal 5 cm of the stomach that DO NOT
cross the esophagogastric junction are
staged using gastric cancer system.
•
Rationale: The 6th edition left the
classification of a tumor as esophageal or
gastric to the discretion of the physician.
Though controversial, the new system
standardizes the classification.
Esophageal cancer. Coronal and axial CECT demonstrate marked thickening
of the gastric cardia with extension into the distal esophagus (green arrows).
Based on the 7th AJCC, this is esophageal cancer as the tumor arises within
the proximal 5 cm of the stomach AND crosses the EG junction.
7TH AJCC GASTRIC CANCER STAGING SYSTEM
UPDATES TO TUMOR STAGING
•
•
Several Tumor (T) categories have been
upstaged.
T-staging of gastric cancer, AJCC 7th manual.
Rationale:
T1a
Tumor invades the lamina propria or muscularis
mucosa. Previously Tis (in situ).
T1b
Tumor invades the submucosa.
T2
Tumor invades the muscularis propria.
T3
Tumor penetrates the subserosal connective
tissue, extends into the gastrohepatic and
gastrocolic ligaments, or into the greater or lesser
omentum, without perforation of the visceral
peritoneum. Previously T2b.
T4a
Tumor invades the serosa (visceral peritoneum).
Previously T3.
T4b
Tumor invades adjacent structures, such as the
spleen, transverse colon, liver, diaphragm,
pancreas, abdominal wall, adrenal gland, kidney,
small intestine, and retroperitoneum.
• T categories have been harmonized with
those of the esophagus, small and large
intestine.
• Tis reclassified as T1a since lymph node
metastasis may be present when tumor is
confined to the lamina propria, due to
abundance of lymphatic channels in the
gastric mucosa.
• T2b has been reclassified as T3, and T3
as T4a to reflect shorter 5-year survival for
subserosal and serosal invasion.
TUMOR STAGING
Anatomically, the stomach has multiple layers,
however on CECT portal venous phase we visualize
only three layers :
•
•
•
• Mucosa
• Muscularis mucosa
• Submucosa
• Muscularis propria
• Subserosa
• Serosa
CT limitations:
Enhancing layer
Hypoenhancing layer
Enhancing layer
•
Limited in differentiating T1a from T1b
•
Limited in differentiating T3 from T4a
T2 TUMOR
T2 tumor: Axial CECT
shows normal layers of the
greater curvature (green
and blue arrows, yellow
star), and diffuse
enhancement and
thickening of the lesser
curvature and gastric
antrum with loss of
hypoenhancing submucosal
stripe (purple arrows).
Adenopathy is present
(white arrow).
EUS is more effective for delineating these stages
Tumor (T) staging by CT:
T1a
Not visible on CT.
T1b
Mucosal thickening and enhancement. Preserved hypoenhancing submucosal
stripe.
T2
Loss of submucosal hypoenhancing stripe.
T3
Contiguous spread of disease into the perigastric ligaments, greater or lesser
omentum.
T4a
Linitis plastica, infiltration of the surrounding peritoneal fat.
T4b
Contiguous spread to adjacent organs and structures.
T2 tumor: Coronal CECT demonstrates circumferential wall
thickening of the gastric antrum with loss of the normal
hypoenhancing submucosal stripe (yellow arrow). Note
normal appearance of gastric fundus (white arrow).
TUMOR STAGING- T3
Gastrohepatic ligament
Hepatoduodenal ligament
T3 tumor: Axial CECT demonstrates lesser
curvature thickening with extension into the
gastrohepatic ligament encasing the left
gastric artery (green arrow).
T3 tumor: Coronal CECT demonstrates
diffuse thickening and enhancement of
the gastric fundus (white arrow) with
extensive extragastric spread of disease
including periportal extension of tumor
along the hepatoduodenal ligament to
the liver with narrowing of the portal vein
(blue arrow). Adenopathy is present
(purple arrows).
Gastrocolic, gastrohepatic and
gastrosplenic ligaments
T3 tumor: Axial CECT demonstrates
diffuse gastric wall thickening with soft
tissue infiltration along the gastrocolic
ligament containing gastroepiploic vessels
(yellow arrow). There is extension into the
gastrohepatic ligament (green arrow) and
into the gastrosplenic ligament containing
short gastric arteries (orange arrow).
TUMOR STAGING- T4A
T4a tumor: Axial CECT
demonstrates linitis plastica
with marked diffuse
thickening and
enhancement of the
stomach invading the
subserosa and serosa
without invading adjacent
structures (red arrow).
T4a tumor. Axial CECT demonstrates marked
thickening of the gastric body and soft tissue
infiltration of the peritoneal fat in the left upper
quadrant (orange arrow). Direct spread along the
gastrohepatic ligament containing left gastric
artery (green arrow), gastrosplenic ligament
containing left gastroepiploic vessels (blue arrow),
and splenorenal ligament containing distal splenic
artery and proximal splenic vein (purple arrow) is
present.
T4a tumor: Axial CECT
shows marked thickening
and enhancement of the
gastric antrum with
infiltration of the peritoneal
fat (orange arrow).
TUMOR STAGING- T4B
T4b tumor: Coronal CECT
demonstrates marked diffuse gastric
thickening invading the left hepatic lobe
(yellow arrow). Tumor extends into the
gastrocolic ligament (brown arrow) and
has metastasized to the liver (pink
arrow).
T4b tumor: Axial CECT
demonstrates asymmetric
mural thickening of the
gastric fundus with soft
tissue infiltration along the
celiac axis (orange arrow)
and left adrenal gland (blue
arrow).
T4b tumor: Axial CECT demonstrates
diffuse mural thickening of the stomach
with fistulization between the gastric body
and a thickened colonic splenic flexure
(green arrow).
T4b tumor: Axial CECT demonstrates marked
diffuse gastric thickening invading the
pancreas (red arrow). Tumor extends along
the hepatoduodenal ligament (peach arrow).
7TH AJCC GASTRIC CANCER STAGING SYSTEM
UPDATES TO NODAL STAGING
• Upstaging in number of involved lymph nodes
• Rationale: In many centers, particularly in the US and Europe,
less than 15 lymph nodes are dissected, limiting the ability to
stage patients. The new system adjusts guidelines.
N- Staging of gastric cancer, AJCC
6th manual
N
N- Staging of gastric cancer, AJCC
7th manual
No regional lymph node metastasis
N0
No regional lymph node metastasis
Metastasis in 1 to 6 regional lymph
nodes
N1
Metastasis in 1 to 2 regional lymph
nodes
Metastasis in 7 to 15 regional lymph
nodes
N2
Metastasis in 3 to 6 regional lymph
nodes
Metastasis in ≥16 regional lymph
nodes
N3
Metastasis in 7 or more regional lymph
nodes
NODAL STAGING
•
High frequency of lymph node involvement at
diagnosis- 5-24% of early gastric cancer (T1) can
have lymph node involvement.
•
Prognosis depends on the total number and
regional versus metastatic location of lymph nodes.
•
Lymph nodes are divided into 23 stations by
Japanese Gastric Cancer Association (JGCA), for
purposes of staging regional (N) versus metastatic
(M) lymph nodes, and for surgical approach.
• 1-6 are perigastric
• 7-18 are adjacent to major vessels, behind the
pancreas, and along the aorta
• 19-20 and 110-112 are around the diaphragm,
supradiaphragmatic, and paraesophageal
•
CT characteristics of abnormal
lymph nodes:
• ≥ 8 mm in short axis
• round shape
• marked or heterogeneous
enhancement
• cluster of 3+ nodes in a
lymph node station
JGCA LYMPH NODE
STATIONS
Regional lymph nodes (LNs) (in gray,
classified as N disease): 1-11, 14v
• Jejunal LNs adjacent to gastrojejunostomy
anastomosis in recurrent cancer after
partial gastrectomy
Distant LNs (in orange, classified as M
disease): 13, 15-20, 110-112
• 12*: Hepatoduodenal lymph nodes are
regional by JGCA, but distant by AJCC.
Group LN station
2
3
4
LN station
Location
7
Left gastric artery trunk
8
Common hepatic artery
9
Celiac artery
10
Splenic hilar
11
Splenic artery
12*
Hepatoduodenal ligament
13
Posterior surface of the pancreatic head
14v
Superior mesenteric vein
15
Middle colic
16
Paraaortic
17
Anterior surface of the pancreatic head
beneath the pancreatic sheath
18
Inferior border of pancreatic body
19
Infradiaphragmatic LNs along
subphrenic artery
20
Paraesophageal LNs in diaphragmatic
hiatus
Location
Perigastric lymph nodes
1
Group
1
Right paracardial
2
Left paracardial
3
Lesser curvature
4
Greater curvature
110
Paraesophageal LNs in lower thorax
5
Suprapyloric
111
Supradiaphragmatic
6
Infrapyloric
112
Posterior mediastinal
NODAL STAGING
•
Lymphatic involvement correlates with
the degree of gastric wall invasion.
Frequently involved lymph nodes by tumor location
•
Lymphatic drainage of the stomach is
complex and multidirectional.
Portion of
stomach
Perigastric lymph
nodes
Non-perigastric
lymph nodes
•
The distribution of nodal metastasis is
variable.
Upper third
- lesser curvature
- paracardial
•
Depending on the location of the primary
tumor – upper, middle and lower third,
certain lymph node stations have a
Middle third
higher frequency of involvement.
- celiac artery
- left gastric artery
- splenic hilum
- para-aortic
- lesser curvature
- greater curvature
- right paracardial
- splenic hilum
- para-aortic
- infrapyloric
- lesser curvature
- greater curvature
- common hepatic
artery
- celiac artery
•
•
Skip metastasis may occur, with
uninvolved perigastric lymph nodes and Lower third
involved metastatic distant lymph nodes.
Upper and middle third tumors have a
higher incidence of skip metastasis.
NODAL STAGING (N) – REGIONAL GROUP 1
Station 3. Axial CECT demonstrates wall
thickening and enhancement of the proximal
lesser curvature, with enlarged lesser curvature
lymph nodes (blue arrow).
Station 4. Axial CECT demonstrates diffuse wall
thickening of the proximal two thirds of the
stomach, and enlarged greater curvature lymph
nodes (yellow arrow).
Stations 5 and 6. Coronal CECT in a patient with
diffuse gastric wall thickening due to chronic
gastritis and a malignant ulcer along the lesser
curvature (green arrow). There is station 5
suprapyloric (pink arrow) and station 6
infrapyloric (orange arrow) adenopathy. An air
and fluid collection is seen subdiaphragmatically
due to perforation (red arrow).
NODAL STAGING (N) – REGIONAL GROUP 2
Station 7. Axial CECT in a patient with
adenocarcinoma of the gastric antrum (not
shown) demonstrates enlarged lymph nodes
along the left gastric artery (green arrow). A
gallbladder mass is present.
Stations 8, 10 and 11. Axial CECT
demonstrates irregular thickening and
enhancement of the lower third of the
stomach (white arrow). There is station 8
common hepatic artery (yellow arrow),
station 10 splenic hilum (green arrow) and
station 11 splenic artery (orange arrows)
adenopathy, as well as right portal vein
thrombosis (blue arrow), and liver metastasis
(red arrow).
Station 9. Axial CECT demonstrates
diffuse thickening of the middle third
of the stomach (white arrow) and
celiac axis adenopathy (peach arrow).
NODAL STAGING (M) – DISTANT LYMPH NODES
Station 12. Coronal CECT demonstrates diffuse wall
thickening and enhancement of the upper two thirds
of the stomach (white arrow), and hepatoduodenal
adenopathy (blue arrow). Regional (N) lymph nodes
are seen in the celiac axis (peach arrow) and
infrapyloric (orange arrow) stations.
Station 16. Coronal CECT demonstrates
diffuse wall thickening of the gastric cardia and
proximal stomach (white arrows), and
extensive paraaortic adenopathy (green
arrows).
Station 15. Axial CECT demonstrates focal
thickening of the distal third of the stomach
(white arrow) and middle colic adenopathy (red
arrows).
LYMPH NODE DISSECTION TYPES
•
D0 dissection- fewer lymph nodes than D1
•
D1 dissection- Group 1 nodes (gray nodes)
•
D2 dissection- Group 1 and 2 nodes (orange nodes
part of D1+ dissection, red nodes included in D2)
•
D3 dissection- Group 1, 2, and 3 nodes
•
D4 dissection- Group 1, 2, 3, and 4 nodes
•
Depending on the type of gastrectomy (distal vs
total), the lymph nodes removed may be modified.
•
Typically the more extended dissections (D2 or D3
and beyond) are performed in Japan and may
account for better survival rates as compared to
Western countries, however, others argue that
extended lymph node dissection is associated with
higher post-operative morbidity and mortality.
4
4
Stomach
6
2
3
5
12
9
8
7
Pancreas
Duodenum
4
1
11p
11d
Spleen
7TH AJCC GASTRIC CANCER STAGING SYSTEM
UPDATES TO METASTASIS AND TNM STAGING
• Peritoneal carcinomatosis/ + peritoneal washing cytology is now M1 disease.
• Only M1 patients may be classified as Stage IV.
• Rationale: patients with peritoneal disease and patients with M1 disease have
significantly worse survival.
M-staging of gastric cancer, American Joint
Committee on Cancer 7th manual
Stage groupings
M0
No distant metastases
M1
Metastasis:
-Distant metastasis
-Involvement of hepatoduodenal, retropancreatic,
mesenteric, retroperitoneal, and para-aortic lymph
nodes are considered distant metastases
-Peritoneal carcinomatosis/ positive peritoneal
washing cytology New from prior system
N0
N1
N2
N3
T1
IA
IB
IIA
IIB
T2
IB
IIA
IIB
IIIA
T3
IIA
IIB
IIIA
IIIB
T4a
IIB
IIIA
IIIB
IIIC
T4b
IIIB
IIIB
IIIC
IIIC
M1 (any T or N)
IV
METASTASIS STAGING
• Distant metastases occur through
multiple mechanisms:
• Hematogenous: liver is the
most common site, other sites
include lung, bones, and
adrenal glands
• Lymphatic: distant nodal
stations, lymphangitic spread
of tumor
• Peritoneal: ascites, soft tissue
plaques or nodules, peritoneal
fat stranding, thickening or
enhancement, Krukenberg
tumor
Hematogenous metastases. Anterior and posterior
Tc99m MDP bone scan images demonstrate multiple
areas of increased radiotracer uptake consistent with
diffuse bone metastases.
METASTASIS STAGING
Lymphatic metastases. Coronal PET and
axial CECT images demonstrate FDGavid gastric mass (green arrow) and
enlarged Virchow nodes in the left axillary
and supraclavicular stations (orange
arrows), consistent with Stage IV disease.
Peritoneal metastases. Coronal CECT
demonstrates a large pelvic mass (purple
arrow) from gastric adenocarcinoma
metastasis to the right ovary (Krukenberg
tumor), and ascites, consistent with Stage
IV disease.
Lymphangitic carcinomatosis. Axial
CECT demonstrates nodular septal
thickening in a patient with gastric
adenocarcinoma, consistent with
Stage IV disease.
Peritoneal carcinomatosis. Axial CECT
demonstrates omental plaques and
nodules (red arrows) in a patient with
gastric adenocarcinoma, consistent
with stage IV cancer.
MANAGEMENT AND PROGNOSIS
•
Accurate staging influences management and is
an important prognostic indicator.
5-year survival rate by stage
N0
N1
N2
N3
• Localized disease is treated with endoscopy,
surgery, and lymph node dissection.
T1
71%
57%
46%
33%
T2
57%
46%
33%
20%
• Locally advanced and systemic disease with
distant metastases is not curable and requires
a combination of surgery, chemotherapy, and
radiation.
T3
46%
33%
20%
14%
T4a
33%
20%
14%
9%
T4b
14%
14%
9%
9%
M1 (any T or N)
4%
Resection options:
Indications:
Endoscopic mucosal resection or endoscopic submucosal
dissection
For early gastric cancer (EGC)- gastric cancer that invades no deeper
than the submucosa, regardless of lymph node metastasis (T1, any N).
Lymph node involvement affects decision for chemotherapy.
Surgical
Total Gastrectomy
- Proximal or upper 1/3 tumors
- Large midgastric or infiltrative tumor (linitis plastica)
Partial/subtotal gastrectomy
- Lower two-third tumors
MANAGEMENT- UNRESECTABLE CANCER
• Unresectable cancers are not curable and typically undergo local or
systemic therapy, or a combination of both, for palliation.
• Features of unresectability:
• Distant metastases
• Invasion of a major vascular structure, such as the aorta
• Disease encasement or occlusion of the hepatic artery or
celiac axis/proximal splenic artery
• Lymph nodes in the aortocaval region, mediastinum, porta hepatis,
or behind or inferior to the pancreas are usually considered
outside of the surgical field
• Linitis plastica
CONCLUSION
• Imaging plays an essential role in the TNM staging of gastric
adenocarcinoma based on updated criteria of AJCC.
• Radiologist knowledge of common patterns of disease spread
based on locoregional pathways and metastatic spread is
essential for management and prognosis.
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Contact information: [email protected]