Introduction
Gastric cancer is the second most common cause of cancer-related death in Indian men
and women aged between 15 and 44 years.[1] Most patients present at an advanced stage of disease. Surgically resectable disease
usually requires a standard gastric resection and D2 lymphadenectomy. Imaging, especially
with computed tomography (CT) scan of abdomen as well as thorax, is necessary for
localization, nodal mapping, and metastatic workup of gastric cancer.
Risk Factors and Etiopathogenesis
Risk factors may differ for proximal and distal gastric cancers. The important risk
factors include gastric adenomas or dysplasia, chronic atrophic gastritis, previous
gastric surgery, Helicobacter pylori infection, high intake of pickled, smoked, salted, or preserved foods, smoking and
alcohol consumption, obesity, and family history.[2]
[3]
[4]
Epidemiology and Clinical Presentation—India and Global
Gastric carcinoma is currently the fifth most common cancer worldwide and accounts
for 8.2% of all cancer-related deaths globally.[5] There is substantial geographic variation in gastric cancer incidence. High age-standardized
incidence rate is seen in the high-income Asia Pacific region (Japan, South Korea),
with incidences of 29.5 per thousand population, followed by Eastern Europe and Andean
Latin America. In contrast, India has relatively low rates of gastric carcinoma, with
an age-standardized incidence rate of 7.5 per 100,000 population.[6] Gastric cancer is the second most common cause of cancer-related death in Indian
men and women aged between 15 and 44 years.[1] Highest incidence is reported from north-eastern and southern parts of India.[7] Most patients present at an advanced stage of disease. Standard gastric resection
and D2 lymphadenectomy offer the best chance of survival. The overall survival for
gastric carcinoma is poor and the 5-year survival rate with surgical treatment alone
ranges between 23 and 25%.[8]
Clinical features of gastric carcinoma include weight loss, persistent abdominal pain,
dysphagia (proximal tumors), gastric outlet obstruction and/or vomiting (distal tumors),
occult gastrointestinal bleeding with or without iron deficiency anemia, and signs
or symptoms of distant metastases that include palpable nodes such as left supraclavicular
node (Virchow's node), periumbilical nodes (Sister Mary Joseph node), and left axillary
node (Irish node). Patients may also present with ascites from peritoneal spread.
Diagnostic Workup
Other than history, physical examination, and cross-sectional imaging, the diagnostic
workup of suspected gastric cancer includes:
-
Complete blood count and comprehensive chemistry profile.
-
Endoscopy and biopsy. In case of metastatic disease, human epidermal growth factor
receptor 2 (HER-2), Programmed cell death protein 1 (PD-1) and Microsatellite instability
(MSI) testing are recommended. Histology should be reported according to the World
Health Organization criteria. A histopathology confirmation is mandatory before definitive
treatment.
-
Biopsy of metastatic disease, as clinically indicated.
-
Staging laparoscopy: Staging laparoscopy can upstage up to 30% of tumors. It is indicated
for stage IB to III gastric cancer (as assessed by clinicoradiological examination)
to determine treatment intent before commencement of neoadjuvant therapy.[9] It is desirable to collect peritoneal washings during laparoscopy.[10]
Imaging Guidelines
Screening
Some countries with high incidence of gastric carcinoma (such as Japan) have national
screening programs. These programs allow early diagnosis of gastric carcinoma when
the disease is potentially curable.[11] Japanese guidelines recommend screening endoscopy for adults more than 50 years
of age.[12]
Diagnosis and Staging
Goal of Imaging
-
Identify resectable disease.
-
Plan resection:
-
Siewert classification (Location of midpoint of the tumor in relation to the gastroesophageal
junction).
-
Determine nodal involvement (N+ or not) and nonregional, metastatic nodes.
-
Vascular and root of mesentery encasement. Encasement of aorta or its major branches,
except splenic artery, is a contraindication to curative surgery.
-
Identify and assess the burden of metastases.
-
Response assessment (following neoadjuvant chemotherapy or palliative chemotherapy)
-
Identify postoperative complications.
Imaging Methods
Endoscopic ultrasound is the most accurate preoperative staging modality of early gastric carcinoma with
an accuracy ranging between 78 and 94%.[13]
Method of choice of cross-sectional imaging for staging of gastric cancer is contrast-enhanced CT (CECT) scan thorax including lower neck, abdomen, and pelvis (CT TAP). CT scans perform better
at T-staging of advanced (T3 and T4) carcinomas versus early (T1 and T2) carcinomas.
Positron emission tomography (PET-CT) evaluation from skull base to midthigh is recommended in locally advanced gastric
cancer for metastatic workup especially if metastases are not evident on conventional
CECT. Routine use of 18F-fluorodeoxyglucose (FDG) PET-CT offers no significant incremental value over and
above CECT as up to one third of cases of gastric cancer are not FDG avid.[7] In one retrospective study, only a small percentage of nodes were spotted in PET-CT
that were not identified by conventional staging CT.[14] Some studies support the use of PET in gastric cancer staging, particularly in characterizing
distant metastases or lymphatic metastases beyond D1 or D2 compartment. In postoperative
cases with suspected recurrence, equivocal findings on CECT can be better characterized
with the added metabolic information of FDG-PET as disease recurrence may be difficult
to identify in some cases due to altered anatomy.
Technique of CECT
CECT for gastric cancer is done in two phases: noncontrast and portal venous phase
([Table 1]). An additional arterial phase is optional and may be helpful in the evaluation
of arterial anatomy and detection of very early lesions. Iodinated contrast media
(Iodine concentration 300/320/350) is usually given as intravenous (IV) contrast at
a dose of 1.5 mL/ kg body weight through the antecubital vein at a rate of 3 mL/s.
Neutral or negative oral contrast is preferred for optimal distension of stomach and
duodenum. Approximately 1,000 to 1,200 mL of plain water usually provide sufficient
distension. Injection Buscopan is not recommended.
Table 1
Imaging parameters of CT scan of abdomen in gastric carcinoma
|
Noncontrast
|
Arterial
|
Portal venous
|
|
Purpose
|
Baseline
|
Vascular anatomy for surgical planning. Delineation of early tumors
|
Extent of tumor, liver metastases, other metastases
|
|
Area covered
|
Xiphisternum to symphysis pubis
|
Xiphisternum to iliac crest
|
Xiphisternum to symphysis pubis
|
|
FOV (mm)
|
422–500
|
380
|
450
|
|
kV
|
100
|
100
|
100
|
|
mAs
|
Auto
|
Auto
|
Auto
|
|
Slice thickness (mm)
|
5
|
5
|
5
|
|
Interslice gap (mm)
|
5
|
5
|
5
|
|
Reconstruction thickness (mm)
|
1
|
1
|
1
|
|
Reconstruction interval (mm)
|
0.5
|
0.5
|
0.5
|
Abbreviations: CT, computed tomography; FOV, field of view.
Primary Tumor Staging
The primary tumor, if identified in CT, is to be described according the following
subheadings:
Site
Gastric cardia, proximal stomach, distal stomach. For proximal tumors, the relation
of the epicenter of the cardia according to the Siewert classification is to be mentioned
([Fig. 1]).
Fig 1 Siewert classification of gastroesophageal junction (GEJ) carcinoma. Type I, epicenter
of the lesion 1 to 5 cm above the GEJ; type II, epicenter of the lesion within a point
1 cm above to a point 2 cm below the GEJ; and, type III, epicenter of the lesion is
2 to 5 cm below GEJ (arrow).
Extent
Focal, segmental, or diffuse.
Size
Three dimensions of focal lesions; maximum length of the involved segment in segmental
lesion.
Relationship with adjacent structures: Involvement of surrounding structures especially
gastrohepatic ligament, duodenum, pancreas, left adrenal, and colon.
Identify periarterial cuffing /thickening along celiac axis and its branches/identify
small perigastric veins and extramural venous invasion; optional).[15]
Nodal Status
Lymphatic spread is found in 74 to 88% of gastric cancers at diagnosis.[16] Presence of nodes in preoperative staging warrants perioperative chemotherapy and
indicates higher chance of local recurrence. In staging CT, nodes larger than 6 to
8 mm in the short axis are considered significant.[17]
Radiology report should mention the location and approximate number of significant
nodes. Dimensions of the largest node are mentioned in two axes. Nodes can be described
in two large groups.
-
Regional (D1 and D2 nodes): Perigastric, along left gastric artery, common hepatic
artery, celiac artery, splenic artery, splenic hilar and hepatoduodenal nodes. Superior
mesenteric vein nodes are also considered regional node.[17]
-
Nonregional nodes: para-aortic, aortocaval, mediastinal, and left supraclavicular
nodes.
Metastasis
Liver, omentum, peritoneum, lungs, bone, ovaries, and rectovesical pouch.
Presence of ascites and if present, its predominant location and nature (attenuation
and internal septations).
Synchronous primary lesion elsewhere in the esophagus or stomach.
Arterial Anatomy
Celiac artery and its branches and any anatomic arterial variation thereof is desirable
to be mentioned in the preoperative evaluation.
Chemotherapy Response Assessment
Assessment of response following perioperative chemotherapy is currently performed
with multidetector computed tomography (MDCT) and/or FDG-PET/CT. On CT, the Response
Evaluation Criteria in Solid Tumors (RECIST) criteria is considered the method of
choice in the assessment of response; however, the primary gastric tumor has been
considered unmeasurable according to RECIST. Response assessment focuses on short
axis measurement of involved lymph nodes and exclusion of disease progression. CT
tumor volumetry (TV) to accurately measure the primary tumor is shown to be useful.
A 15% reduction in tumor volume evaluated with MDCT has been shown to correlate with
histologic response.[18] FDG-PET/CT is not routinely used for treatment response. More evidence is needed
to use Positron Emission Tomography (PET) Response Criteria in Solid Tumors criteria
in chemotherapy follow-up.[19]
Postoperative Imaging
Most advanced gastric carcinoma requires neoadjuvant chemotherapy followed by proximal,
distal, subtotal or total gastrectomy, depending upon site and location of malignancy.
Other than response evaluation following surgery and subsequent chemotherapy, if any,
imaging is necessary in cases in immediate or early postoperative period.
Gastrectomy with D2 lymph node clearance is associated with postoperative complications
such as bleeding, anastomotic leak, sepsis, duodenal blow out, intestinal obstruction,
and pulmonary complications. If the patient deviates from the normal recovery pathway
in the postoperative period, then the patient may require imaging.
Often a noncontrast CT of abdomen and pelvis is sufficient. Oral contrast is given
when obstruction or leak is suspected. IV contrast is given when bleeding is suspected.
Reporting checklist of a postoperative CT in gastric cancer includes:
-
Pleural effusion or basal atelectasis.
-
Any collection at perioperative site or anastomotic site.
-
Status of bowel (small/large bowel) dilatation/narrowing.
-
Area of stenosis or narrowing or abnormal wall thickening in anastomotic site or bowel
and to look for normal passage of oral contrast.
-
Look for a stoma site, if any.
-
Look for intra-abdominal drains and their position.
-
Ascites.
Principles of Management
Surgery
Resectable Lesions
The standard oncological resection for gastric cancer involves resection of at least
two-thirds of the stomach along with D2 lymph node clearance. The type of resection
depends on the location of the tumor, which includes total gastrectomy (includes cardia
and pylorus), distal gastrectomy (two-thirds of distal stomach), and proximal gastrectomy
(including gastro-esophageal junction).[20] A proximal resection margin of at least 3 cm is recommended for mass-forming and
ulcerative lesions and of at least 5 cm of the same for infiltrative lesions. En bloc
resection of the gastric cancer along with resection of left lateral section of liver,
spleen, tail of pancreas, diaphragm can be done to achieve R0 resection. However,
in cases of involvement of the second portion of duodenum, an extended resection of
the head or body of the pancreas or the hepatoduodenal ligament is not recommended.
Nodal resection: D1: perigastric nodes; D2: nodes along left gastric artery (LGA),
common hepatic artery (CHA), splenic artery, and celiac axis.
Splenectomy is indicated when there is direct splenic involvement from a greater curvature
tumor.
For selected cases of peritoneal carcinomatosis (low volume peritoneal metastases
or isolated cytology positive), a multimodal and aggressive treatment, including neoadjuvant
chemotherapy (systemic, intraperitoneal, or a combination of these), curative gastrectomy,
D2 lymphadenectomy along hyperthermic intraperitoneal chemotherapy can be beneficial.[21]
Palliative Surgery
Palliative surgery is only indicated for relieving symptoms like bleeding or obstruction
in presence of metastases. There is no advantage of cytoreductive surgery over palliative
chemotherapy in the presence of metastatic disease.[22] Gastrojejunostomy is preferred over stenting in cases of obstruction, if surgery
can be done, and prognosis is reasonable. Nodal resection not indicated.
Interventional Radiology
Role of interventional radiology is limited to embolization for bleeding that is not
controlled by endoscopic methods or relieving of obstruction by placement of a stent
or gastrostomy tube.
Chemotherapy and Immunotherapy
In case of localized or locally advanced disease, the treatment intent becomes curative.
The current standard of care is FLOT regime (fluorouracil, leucovorin, oxaliplatin,
and docetaxel), which comprises four cycles of neoadjuvant FLOT chemotherapy followed
by surgery and another four cycles of FLOT. FLOT has shown to increase overall survival
compared with the ECF/ECX (epirubicin-cisplatin-capecitabine), the previous standard
of care (hazard ratio: 0·77; 95% confidence interval: 0.63–0·94].[23] In case of metastatic cancer, the treatment depends on the combined positive score.
If it is high, there is a role of immunotherapies like pembrolizumab/nivolumab in
combination with a standard CAPOX/FOLFOX-based regimen to improve overall survival.
Treatment depends on PD-L1 combined positive score. In case of low immune score, the
standard of care remains chemotherapy alone.[24]
[25] In the case of HER 2 positive tumors, adding trastuzumab with standard chemotherapy
regimens has shown to improve survival.[26]
[27]
Follow-Up Imaging
For early disease (pTi, pT1) treated by endoscopic resection, CT TAP is indicated
only when there is clinical concern for recurrence. In cases of pathological (Yp)
stage I to III cases, CT TAP every 6 to 12 months is indicated for 2 years, then annually
for up to 5 years.
