This document provides information on the diagnosis of gastric cancer. It discusses: - Endoscopy as the main diagnostic tool, with biopsy having a sensitivity of over 90% for detecting gastric cancer. Multiple biopsies should be taken. - Diffuse gastric cancers can be hard to detect with endoscopy alone, and barium studies may reveal abnormalities in these cases. - Follow up endoscopy 8-12 weeks after initial endoscopy is recommended by some guidelines to verify healing, with biopsies of any remaining ulcers. - No serologic markers have proven sufficiently sensitive or specific for diagnosis, though some show increased risk of gastric cancer.

1. Diagnosis of Gastric
Cancer
Prof. Ahmed M BadheebProf. Ahmed M Badheeb

2. Epidemiology of gastric cancer
 GC remains one of the most common forms ofGC remains one of the most common forms of
cancer worldwidecancer worldwide
 ~ 9.9% of new cancers~ 9.9% of new cancers
 ~ 870,000 new cases and 650,000 deaths/ yr~ 870,000 new cases and 650,000 deaths/ yr
 ~ 21,860 pts were diagnosed in 2006 in the US of~ 21,860 pts were diagnosed in 2006 in the US of
whom 11,430 are expected to die.whom 11,430 are expected to die.
Ferlay, Gobocan 2000: Lyon, IARCPress.Ferlay, Gobocan 2000: Lyon, IARCPress.

3. Atrophic gastritisAtrophic gastritis
 Risk of developing GC during 4.4 yrs of follow-upRisk of developing GC during 4.4 yrs of follow-up
period was increased 5.7-foldperiod was increased 5.7-fold
Correa, P. Cancer 1982; 50:2554Correa, P. Cancer 1982; 50:2554
 Hypochlorhydria microbial colonization, someHypochlorhydria microbial colonization, some
of which possess nitrate reductase, allowingof which possess nitrate reductase, allowing
nitrosation that is genotoxic.nitrosation that is genotoxic.
 Loss of endocrine cells, which normally secreteLoss of endocrine cells, which normally secrete
EGF and TGF, thereby aiding the stomach inEGF and TGF, thereby aiding the stomach in
regenerating damaged tissue.regenerating damaged tissue.
Risk factors
Precursor lesions

4. Intestinal metaplasia/ dysplasia
 H. pylori, bile reflux, induced experimentally byH. pylori, bile reflux, induced experimentally by
irradiationirradiation
 More frequent in countries with high incidence of GCMore frequent in countries with high incidence of GC
 Most pts with HG dysplasia already have or soonMost pts with HG dysplasia already have or soon
develop GCdevelop GC
 In gastrectomy specimens for GC, 20-40 % of ptsIn gastrectomy specimens for GC, 20-40 % of pts
had dysplasia and GC developed at 21% for mild,had dysplasia and GC developed at 21% for mild,
and 57% for severe dysplasiaand 57% for severe dysplasia
Shimoyama, Virchows Arch 2000; 436:585.Shimoyama, Virchows Arch 2000; 436:585.

5. Environmental factors
Diet
 Nitrates nitroso compounds.Nitrates nitroso compounds.
 Diets low in vegetables, fruits, milk, and vit A andDiets low in vegetables, fruits, milk, and vit A and
high in fried food, processed meat, and fish.high in fried food, processed meat, and fish.
 Vitamin C reduce the formation of carcinogenic n-Vitamin C reduce the formation of carcinogenic n-
nitroso compounds inside the stomach.nitroso compounds inside the stomach.
 High salt intake damages stomach mucosa andHigh salt intake damages stomach mucosa and
increases the susceptibility to carcinogenesis inincreases the susceptibility to carcinogenesis in
rodents.rodents.

6.  SmokingSmoking
The risk was increased by 1.5 to 1.60-foldThe risk was increased by 1.5 to 1.60-fold
 AlcoholAlcohol
Not been demonstratedNot been demonstrated
 Socioeconomic statusSocioeconomic status
2-fold increase in populations with low socioeconomic status2-fold increase in populations with low socioeconomic status
 Gastric surgeryGastric surgery
Relative risk in the range of 1.5 to 3.0,Relative risk in the range of 1.5 to 3.0,
 Helicobacter pyloriHelicobacter pylori
6-fold increase in the risk of GC6-fold increase in the risk of GC

7. Host-related factors
 Blood group A.Blood group A.
20% excess of GC than those of group O, B, or AB.20% excess of GC than those of group O, B, or AB.
 Familial predisposition.Familial predisposition.
 GC has been described in association with certainGC has been described in association with certain
cancer syndromes (HNPCRC, FAP, Peutz Jeghers).cancer syndromes (HNPCRC, FAP, Peutz Jeghers).
 There are reports of at least 45 families worldwideThere are reports of at least 45 families worldwide
withwith hereditary diffuse gastric cancerhereditary diffuse gastric cancer due to germlinedue to germline
mutations of the e-cadherin gene CDH1.mutations of the e-cadherin gene CDH1.
Blair, Clin Gastroenterol Hepatol 2006; 4:262.Blair, Clin Gastroenterol Hepatol 2006; 4:262.

8. Model of gastric carcinogenesis
Adapted from Elder, JB. Carcinoma of the stomach.
Gastroenterology, 5th ed, WB Saunders, Philadelphia, 1995, p. 862.

9. Clinical Features
 Most GCs are diagnosed in symptomatic ptsMost GCs are diagnosed in symptomatic pts
presenting with advanced incurable disease.presenting with advanced incurable disease.
 Surgically curable lesions are usually asymptomatic,Surgically curable lesions are usually asymptomatic,
and rarely detected outside a screening program.and rarely detected outside a screening program.
 Weight loss and persistent abdominal pain are theWeight loss and persistent abdominal pain are the
most common symptoms at initial diagnosis.most common symptoms at initial diagnosis.
Ann Surg 1993; 218:583.Ann Surg 1993; 218:583.

10. Presenting symptoms in 18,363 pts
Adapted from Wanebo, HJ, Kennedy, BJ, Chmiel, J, et al,Adapted from Wanebo, HJ, Kennedy, BJ, Chmiel, J, et al,
Ann Surg 1993; 218:583.Ann Surg 1993; 218:583.
SymptomSymptom PercentPercent
Wt lossWt loss 6262
Abdominal painAbdominal pain 5252
NauseaNausea 3434
DysphagiaDysphagia 2626
MelenaMelena 2020
Early satietyEarly satiety 1818
Ulcer type painUlcer type pain 1717

11.  ~ 25% of pts have a history of GU.~ 25% of pts have a history of GU.
 Pseudoachalasia syndrome may occur as thePseudoachalasia syndrome may occur as the
result of involvement of Auerbach's plexus.result of involvement of Auerbach's plexus.
Kahrilas, am J med 1987; 82:439Kahrilas, am J med 1987; 82:439..
 Feculent emesis or passage of recentlyFeculent emesis or passage of recently
ingested material in the stool.ingested material in the stool.
 Occult GI bleeding with or without ID anemiaOccult GI bleeding with or without ID anemia..

12. Signs of tumor extension
 Palpable abdominal massPalpable abdominal mass
 Periumbilical nodule (sister Mary Joseph's node) or ltPeriumbilical nodule (sister Mary Joseph's node) or lt
supraclavicular LN (Virchow's node).supraclavicular LN (Virchow's node).
Morgenstern, am J Surg 1979; 138:703Morgenstern, am J Surg 1979; 138:703
 Peritoneal spreadPeritoneal spread
 Krukenberg's tumorKrukenberg's tumor
 Blumer's shelf (mass in the cul-de-sac on PR)Blumer's shelf (mass in the cul-de-sac on PR)
Gilliland,. Br J Surg 1992; 79:1364.Gilliland,. Br J Surg 1992; 79:1364.

13.  Ascites can be a manifestation of peritonealAscites can be a manifestation of peritoneal
carcinomatosis,carcinomatosis,
 Palpable liver mass can indicate metastases.Palpable liver mass can indicate metastases.
 Jaundice or clinical evidence of liver failure isJaundice or clinical evidence of liver failure is
seen in the preterminal stages of metastaticseen in the preterminal stages of metastatic
disease.disease.
Fuchs, N Engl J Med 1995; 333:32.Fuchs, N Engl J Med 1995; 333:32.

14. Paraneoplastic manifestations
 Rarely seen at initial presentation.Rarely seen at initial presentation.
 Dermatological findings:Dermatological findings:
 Sign of Leser-Trelat.Sign of Leser-Trelat.
Sudden appearance of diffuse seborrheic keratoses.Sudden appearance of diffuse seborrheic keratoses.
 Acanthosis nigricans.Acanthosis nigricans.
Velvety and darkly pigmented patches of skin folds.Velvety and darkly pigmented patches of skin folds.
 Neither finding is specific for gastric cancer.Neither finding is specific for gastric cancer.
Dantzig, arch Dermatol 1973; 108:700.Dantzig, arch Dermatol 1973; 108:700.

15.  Microangiopathic hemolytic anemiaMicroangiopathic hemolytic anemia
 Membranous nephropathyMembranous nephropathy
 Hypercoagulable states (Trouseau'sHypercoagulable states (Trouseau's
syndrome)syndrome)
 Polyarteritis nodosaPolyarteritis nodosa
Poveda, J Intern Med 1994; 236:679.Poveda, J Intern Med 1994; 236:679.

16. DIAGNOSIS
 Initial diagnosisInitial diagnosis
 Upper endoscopyUpper endoscopy
 Barium studiesBarium studies
 StagingStaging
 CT scanCT scan
 EUSEUS
 LaparoscopyLaparoscopy

17. Upper GI endoscopy
 The mainstay for diagnosis of GC.The mainstay for diagnosis of GC.
 The sensitivity and specificity is > 90%.The sensitivity and specificity is > 90%.
 More sensitive and specific than alternatives.More sensitive and specific than alternatives.
 The ability to perform Bx during endoscopyThe ability to perform Bx during endoscopy
adds to its clinical utility.adds to its clinical utility.
Graham, Gastroenterology 1982; 82:228.Graham, Gastroenterology 1982; 82:228.

18. Malignant and benign gastric ulcer
Malignant GU
of the cardia.
• absence of folds
radiating to the base
•exophytic appearance.
Benign GU in
the prepyloric region.
•well- circumscribed
•folds radiating to
the ulcer base.

19. Endoscopic appearances of gastric
cancer
Adenocarcinoma in the
antrum
(friable, ulcerated,
and circumferential mass)
Adenocarcinoma
of the cardia.
(large, lobulated,
ulcerated mass)

20.  Since up to 5 % of malignant ulcers maySince up to 5 % of malignant ulcers may
appear benign grossly, it is imperative that allappear benign grossly, it is imperative that all
such lesions be evaluated histologicallysuch lesions be evaluated histologically
 These data provide a strong rationale forThese data provide a strong rationale for
upper endoscopy as the initial diagnostic testupper endoscopy as the initial diagnostic test
for pts in whom gastric cancer is suspected.for pts in whom gastric cancer is suspected.
Karita, Gastrointest Endosc 1994; 40:749.Karita, Gastrointest Endosc 1994; 40:749.

21. Endoscopic techniques
 A single Bx has a 70 % sensitivity forA single Bx has a 70 % sensitivity for
diagnosing GCdiagnosing GC
 Performing 7 biopsies from the ulcer marginPerforming 7 biopsies from the ulcer margin
and base increases the sensitivity to > 98 %.and base increases the sensitivity to > 98 %.
 Its important to take numerous Bx fromIts important to take numerous Bx from
smaller, benign-appearing GUsmaller, benign-appearing GU

22.  Diffuse-type GC, so called "linitis plastica," can beDiffuse-type GC, so called "linitis plastica," can be
especially difficult.especially difficult.
 Stiff, "leather-flask" appearing stomach on bariumStiff, "leather-flask" appearing stomach on barium
meal may be associated with a normal endoscopy.meal may be associated with a normal endoscopy.
 These tumors tend to infiltrate the submucosa, soThese tumors tend to infiltrate the submucosa, so
superficial mucosal biopsies may be falsely negative.superficial mucosal biopsies may be falsely negative.
 The combination of strip and bite Bx techniques.The combination of strip and bite Bx techniques.

23. Linitis plastica of the stomach
Fixed narrowing of the entire proximal stomach (arrows)
due to submucosal invasion by a GC.

24. Brush cytologyBrush cytology
 Increases the sensitivity of single biopsies, but theIncreases the sensitivity of single biopsies, but the
extent to which it enhances diagnostic yield when 7extent to which it enhances diagnostic yield when 7
biopsies are obtained remains unknownbiopsies are obtained remains unknown
 If bleeding with Bx is of concern, it is reasonable toIf bleeding with Bx is of concern, it is reasonable to
brush the ulcer base, since the risk of bleeding frombrush the ulcer base, since the risk of bleeding from
this technique is negligiblethis technique is negligible
Wang, Acta Cytol 1991; 35:195Wang, Acta Cytol 1991; 35:195

25. Follow up endoscopy for GU
 Follow-up endoscopy remains controversial.Follow-up endoscopy remains controversial.
 Most of the literature supporting the need forMost of the literature supporting the need for
follow-up of GU is based on older surgicalfollow-up of GU is based on older surgical
and radiologic, rather than endoscopic data.and radiologic, rather than endoscopic data.
 More recent studies have called into questionMore recent studies have called into question
the common practice of repeating endoscopy.the common practice of repeating endoscopy.

26.  The issue of whether it is cost-effective toThe issue of whether it is cost-effective to
routinely perform repeat endoscopy for allroutinely perform repeat endoscopy for all
gastric ulcers needs to be determined.gastric ulcers needs to be determined.
 The American Society of GI EndoscopyThe American Society of GI Endoscopy
recommends follow-up endoscopy 8 to 12recommends follow-up endoscopy 8 to 12
weeks after initial endoscopy and initiation ofweeks after initial endoscopy and initiation of
therapy to verify healing, with repeat biopsiestherapy to verify healing, with repeat biopsies
performed on remaining ulcers.performed on remaining ulcers.
Gastrointest Endosc 1988; 34:21SGastrointest Endosc 1988; 34:21S..

27. Serologic markers
 No serologic markers have been proven to be useful.No serologic markers have been proven to be useful.
 Increases in serum pepsinogen II.Increases in serum pepsinogen II.
 Decreases in the pepsinogen I: pepsinogen II ratio.Decreases in the pepsinogen I: pepsinogen II ratio.
Has been used in screening programs to identify ptsHas been used in screening programs to identify pts
at increased risk for GC but are insufficientlyat increased risk for GC but are insufficiently
sensitive or specific for establishing a diagnosis.sensitive or specific for establishing a diagnosis.
Harie,. Cancer 1996; 77:991.Harie,. Cancer 1996; 77:991.

28. Barium studies
 Can identify both malignant GUs and infiltratingCan identify both malignant GUs and infiltrating
lesionslesions
 Some early gastric cancers also may be seenSome early gastric cancers also may be seen
 However, false negative barium studies can occur inHowever, false negative barium studies can occur in
as many as 50 % of casesas many as 50 % of cases
 This is a particular problem in early GC in which theThis is a particular problem in early GC in which the
sensitivity of barium meals may be as low as 14 %sensitivity of barium meals may be as low as 14 %
Dooley, CP Ann intern med 1984; 101:538Dooley, CP Ann intern med 1984; 101:538

29. Early gastric cancer
superficial ulcer in the gastric antrum (arrow)
with thickened folds radiating towards the ulcer.

30. Malignant and benign gastric ulcer
Malignant GU of the distal LC.
biconvex meniscus sign with
a nodular ulcer mound
Benign GU of the LC
ulcer crater has smooth margins
and projects beyond gastric wall

31. Staging
 Accurate tumor staging appropriateAccurate tumor staging appropriate
treatment.treatment.
 TNM staging system of the AJCCTNM staging system of the AJCC
 Methods:Methods: CT scanCT scan
EUSEUS
laparoscopylaparoscopy
PET scanPET scan

32. American Joint Committee on Cancer
(AJCC) TNM Staging Classification for GC

33. CT scan
 Recent data have shown the following results with CTRecent data have shown the following results with CT
scanning for staging of GC:scanning for staging of GC:
 Accurate staging — 40 to 50 %Accurate staging — 40 to 50 %
 Understaging as the depth of invasion isUnderstaging as the depth of invasion is
underestimated — 10 to 35 %underestimated — 10 to 35 %
 Overstaging as the depth of invasion isOverstaging as the depth of invasion is
overestimated — 6 to 14 %overestimated — 6 to 14 %
Botet Radiology 1991; 181:419.Botet Radiology 1991; 181:419.

34.  The accuracy of determining LN involvementThe accuracy of determining LN involvement
is no better, with overall accuracy ratesis no better, with overall accuracy rates
between 50-60%.between 50-60%.
 CT is better for evaluating more widelyCT is better for evaluating more widely
metastatic disease, especially liver mets;metastatic disease, especially liver mets;
however, the risk of false positive and falsehowever, the risk of false positive and false
negative results still exists.negative results still exists.
Sussman, Radiology 1988; 167:33Sussman, Radiology 1988; 167:33

35. Endoscopic ultrasonography
 Newer and more accurate means of preoperativeNewer and more accurate means of preoperative
staging of GC.staging of GC.
 Has low risk, although it is more invasive than CTHas low risk, although it is more invasive than CT
 Risk of serious complications of 0.3 %, most of whichRisk of serious complications of 0.3 %, most of which
occurred in the setting of obstructing esophagealoccurred in the setting of obstructing esophageal
tumors.tumors.
Pollack, BJ, EUS. Semin Oncol 1996; 23:336.Pollack, BJ, EUS. Semin Oncol 1996; 23:336.

36.  Pooled data for over 2000 pts who underwent EUSPooled data for over 2000 pts who underwent EUS
found an accuracy of 77% for staging the depth offound an accuracy of 77% for staging the depth of
invasion and 69% for nodal stageinvasion and 69% for nodal stage
 Most inaccuracies are due to understaging nodalMost inaccuracies are due to understaging nodal
involvement and the depth of invasioninvolvement and the depth of invasion
 Distinguishing T2 from T3 lesions is especiallyDistinguishing T2 from T3 lesions is especially
difficult.difficult.

37.  Although EUS has been shown to accuratelyAlthough EUS has been shown to accurately
assess the presence of distant mets in oneassess the presence of distant mets in one
report, its field of vision is only 5 to 7 cm andreport, its field of vision is only 5 to 7 cm and
its utility for this purpose is still in question.its utility for this purpose is still in question.
 EUS guided FNA of suspicious nodes andEUS guided FNA of suspicious nodes and
regional areas is being evaluated, and mayregional areas is being evaluated, and may
further add to its accuracyfurther add to its accuracy
Chang, JJ,. Gastrointest Endosc 1994; 40:694Chang, JJ,. Gastrointest Endosc 1994; 40:694..

38. Laparoscopy
 Laparoscopy, while more invasive than CT or EUS,Laparoscopy, while more invasive than CT or EUS,
has the advantage of directly visualizing the liverhas the advantage of directly visualizing the liver
surface, the peritoneum, and local LNs.surface, the peritoneum, and local LNs.
 It is a sensitive modality for diagnosing liver metsIt is a sensitive modality for diagnosing liver mets
and, in one review, it diagnosed peritoneal mets inand, in one review, it diagnosed peritoneal mets in
23% of pts in whom no such involvement was seen23% of pts in whom no such involvement was seen
by CT.by CT.
Conlon, KC, Semin Oncol 1996; 23:347.Conlon, KC, Semin Oncol 1996; 23:347.

39. Summary
 The ultimate choice of staging modalities is largelyThe ultimate choice of staging modalities is largely
dependent upon pt selection and local expertise.dependent upon pt selection and local expertise.
 CT should be performed to look for M disease, itCT should be performed to look for M disease, it
should not be relied upon for assessing T or N.should not be relied upon for assessing T or N.
 Paracentesis should be performed when ascites isParacentesis should be performed when ascites is
detected.detected.

40.  Liver lesions on CT should be biopsiedLiver lesions on CT should be biopsied
 Laparoscopy should be considered in selected ptsLaparoscopy should be considered in selected pts
 EUS is better than CT at assessing tumor depth andEUS is better than CT at assessing tumor depth and
perhaps LN, particularly if FNA is performedperhaps LN, particularly if FNA is performed

41.  Its use has been shown to alter therapy in ~ 1/3 ofIts use has been shown to alter therapy in ~ 1/3 of
ptspts
 At present, the use of EUS depends largely uponAt present, the use of EUS depends largely upon
local availability and expertiselocal availability and expertise
 Any pt with good PS ultimately requires laparotomyAny pt with good PS ultimately requires laparotomy
for curative or palliative surgery unless unresectabilityfor curative or palliative surgery unless unresectability
is clearly demonstrated.is clearly demonstrated.