ANATOMY, LYMPHATIC DRAINAGE, PATHOLOGY, DIAGNOSIS AND MANAGEMENT OF CA STOMACH

1. BY Dr DEEPAK KUMAR DAS
MOD- Dr NARENDRA KUMAR
PGIMER, CHANDIGARH

4. EPIDEMIOLOGY
 Carcinoma stomach is the 2nd leading cause of cancer related death
behind lung cancer.
 The highest incidences are found in East Asia (Japan and China)>
South America > Eastern Europe
RISK FACTORS
ACQUIRED FACTORS
 H. Pylori infection ( 3-6 times)- distal gastric cancer and intestinal type
 High intake of smoked and salted foods
 Nitrates
 Diet low in fruits and vegetables
 Smoking
 Obesity proximal gastric lesions
 Barrett esophagus/GERD
 Prior subtotal gastrectomy (25%)
 RT exposure

5. GENETIC FACTORS
 E- cadherin (CDH-1 gene)
 Type A blood group
 Pernicious anemia (5-10%)
 HNPCC
 Li-Fraumeni syndrome

6. PATHOLOGICAL CLASSIFICATION OF GASTRIC CANCER
 Adenocarcinoma- 90 to 95%
 Lymphoma
 GIST
 Adenocanthoma
 Squamous cell carcinoma

7. LAURENS CLASSIFICATION
 2 histological types of adenocarcinoma
INTESTINAL TYPE
 Differentiated cancer with tendency to form glands
 Occur in the distal stomach
 Arise from precursor lesions seen mostly in endemic areas and in older
people
 More common in males
 Risk factor is maily inflammatory and enviornmental factors
DIFFUSE TYPE
 Less differentiated- signet ring cell, mucin producing
 Have extensive submucosal and distant spread
 Tend to be proximal
 More common in women and younger people
 Genetic etiology

8.  1926, 4 macroscopic tumor growth
patterns:
 Type I, nodular polypoid tumor without
ulceration and usually with a broad base;
 Type II- fungating, exophytic,
circumscribed tumor with defined sharp
margins, devoid of ulceration except at its
dome
 Type III- ulcerating tumor + penetrating,
infiltrating ulcer base;
 Type IV - diffuse thickening of the gastric
wall with no discretely marginated mass or
ulceration,leather bottle,linitis plastica.
BORRMAN’S CLASSIFICATION

9.  DIRECT- Omenta, Pancreas, Diaphram, Transverse colon,
Mesocolon, Duodenum, Jejunum, Spleen, Liver, Adrenals,
Kidney.
 LYMPHATICS- submucosal to oesophagus and duodenum-
 Initial along greater and lesser curvature,
 Primary drain to all three branches of celiac axis- L gastri,
Comm Hepatic, Splenic ,
 Lately to - hepato duodenal, peripancreatic, root of mesentry
periaortic, middle colic.
 HEMATOGENOUS- liver lung
 PERITONEAL INVOLVEMENT
PATHWAYS OF SPREAD

10. CLINICAL PRESENTATION
 Loss of appetite
 Early satiety
 Abdominal discomfort
 Unintentional weight loss
 Nausea and vomiting
 Tarry stool
 Duration of symptom is <3 months in almost 40% of patients and > 1
year in 20%.
PHYSICAL EXAMINATION
Can reveal advanced disease
- Abdominal mass
-Epigastric or liver mass, periumbilical node (Sister Mary Joseph
node)
- Palpable left supraclavicular node (Virchow’s node)
- Rectal shelf (Blumer’s shelf)

11. DIAGNOSTIC WORK UP
UGIE
- Direct visualisation, cytology and biopsy
yields the diagnosis in >90% of exophytic
lesions
- Infiltrative( linitis plastica), small (<3 cm),
or cardia lesions may be more difficult to
diagnose endoscopically.
EUS
-Most accurate method of determining
depth of tumour invasion (intramural v/s
extramural extension)
- Less accurate in detecting regional nodal
metastasis.

12. -5 layers are seen on EUS
- Layers 1,3 and 5 are hyperechoic and layers 2 and 4 are
hypoechoic.
Layer 1- superficial mucosa
2-deep mucosa
3- submucosa
4- muscularis propria
5- subserosa fat and serosa
White arrow- tumour invasion Black arrow- muscularis propria

13. CONTRAST RADIOLOGY
 Single Contrast/ Double Contrast
 Barium Meal
 Advantages
 Sensitivity comparable to endoscopy
 Non Invasive procedure
Findings in ca stomach
 Irregular filling defect
 Loss of rugosity
 Delayed emptying
 Dilatation of stomach in carcinoma pylorus
 Decreased stomach capacity in linitis plastica

14. Normal double contrast barium
syudy
Carcinoma of gastric antrum

15. CECT CHEST, ABDOMEN AND PELVIS
- Abdominal extent of the disease
- Distant metastasis
- Involvement of celiac or periaortic nodes or extragastric disease( help to
determine which lesions extend to surgically resectable structures)
- Little value in ruling out peritoneal seeding.

16. DIAGNOSTIC LAPOROSCOPY
 To stage the disease especially in locally advanced
tumours
 Peritoneal secondaries
 Occult metastases
 Organ invasion
 Peritoneal lavage for cytology
 Biopsy of peritoneum and nodes

17. PET CT
 Only arround two third of primary tumors are FDG
avid
 GLUT-1 transporter rarely present on subtypes- signet
ring and mucinous tumours
 Too many false negatives
 Lower sensititivity and higher specificity than CT in
detecting LNs

20.  Tumor Extent- most important
 Local
 Metastatic
 Lymph node-
 Number
 location
 Grade & pathological appearance- some relevance
 Biology
 Aneuploidy – cardia
 Diffuse tumors- Linitis plastica
PROGNOSTIC FACTORS

21. TREATMENT GROUPS
 Locoregional carcinoma-
Stage I-III or M0
Potentially resectable disease in medically
fit pts who are able to tolerate major abdominal
surgery.
Unresectable disease in medically fit pts
Medically unfit pts.
 Metastatic ca- stage IV / M1

22. TREATMENT OPTIONS
 Surgery - Primary treatment
 Radiation – Adjuvant/palliative
 CCT- Adjuvant/palliative
 Chemoradiation- Adjuvant
 Basic supportive care.

23. SURGERY
PRINCIPLE
Complete resection of tumor with 5 cm margin
proximally and distally.
 R0 – no macroscopic or microscopic tumor at
resection margins.
 R1 – microscopic margins +ve.
 R2 – macroscopic margins +ve.
 AIM - R0 resection always.

24. SURGERY
 Primary treatment of gastric cancer
 OPTIONS-
 Radical Total Gastrectomy –
 Diffuse involvement
 Proximal involvement.
 Radical Subtotal Gastrectomy –
 Distal cancers,
 Equivalent survival
 Lesser complications
 In proximal cancer, total gastrectomy is
not necessary when subtotal gastrectomy
will provide a 5 cm clearance of the gross
tumour.

25. Endoscopic Mucosal Resection
T1 early lesions that are padunculated
Well differentiated
Small size <3cm
No submucosal involvement- chance of LN involvement-
<5%
SPLENECTOMY
Splenectomy is sometimes performed, particularly in cancers
of proximal third of stomach and tumours of the body near the
greater curvature
Cancers in these locations are more likely to metastasize to
lymph nodes in the splenic hilum that can not be excised
without splenectomy.
Retrospective Japanese and American data do not provide
evidence of survival benefit with the routine use of this
procedure.

26. LN DISSECTION

27.  D1 – Perigastric node( Station 1-6)
 D2 –D1+ perarterial nodes(left gastric, hepatic, celiac, splenic)(7-11)
 D3- D2+ hepatoduodenal, peripancreatic, mesenteric root, portocaval,
P-A nodes, middle colic(13-16)
 D2 to D3 – extended or systemic lymphadenectomies (ELND)
 D0-D1- conservative/limited lymphadenectomies(CLND)
 PRINCIPLE- Dissect the echelon of nodes a level higher than the
highest level of known metastasis;
 Controversy-balancing the benefits of a more extensive, complete
lymphadenectomy with the associated higher risk of
morbidity/mortality.

28. WILL ROGERS PHENOMENON
Diff. in survival b/w Japan & West-
STAGE MIGRATION.
 Extensive pathologic LN evaluation leads to upstaging & subsequent
statistical improvements in overall survival when compared stage for
stage.
 Western patients would be staged inappropriately "low" because of
failure to examine node-bearing areas accurately, affecting the outcome
toward a worse prognosis.
CURRENT STATUS OF LN DISSECTION
 ELND improves the quality of staging, allowing standardization of
prognostic factors and survival data worldwide.
 Routine D2 lymphadenectomy is difficult to justify based on available
evidence.
 Issues- patient selection, surgeon experience, ?survival benefit.
 Minimum, D1 lymphadenectomy should include pathologic
examination of at least 15 nodes.

29. RELAPSE PATTERN AFTER CURATIVE RESECTION
 Cure Rates with surgery alone not adequate.
 High rates of both LRR & distant metastasis.
 T1-T2/N0 only had adequate cure with surgery alone- 90%.
 Radical surg + ELND, does not prevent relapses.
 Subsequent relapse within the site of a prior ELND was
frequent,=>incomplete LN and lymphatic excision.
 Progressive extension of surgery => min. increase in cure rates, offset
by a corresponding increase in operative mortality.
Incidence and patterns of Local relapse predictable based on
anatomical factors, pathways of tumour spread, initial extent of
disease, and anatomic limitations for surgery.
 Distant failures also common.
 Combinations of chemotherapy and irradiation are necessary to alter
both short- and long-term survival.

30. PATTERN OF RELAPSE

31. Pattern of failure in University of Minnesota reoperative series with superimposed
Ideal radiation field and relationship to dose limiting organs

32. RADIOTHERAPY
 Post op XRT
 Pre op XRT
 Intraoperative RT
 Palliative RT
Indications-
 T3-4 resectable disease
 Margins positive
 Residual disease
 LN +ve disease
 Inoperable

33. RADIOTHERAPY TARGET
 Idealized portals from patterns of failure data need modification
individually for patient's initial extent of disease.
 Gastric/tumor bed, anastomosis and gastric remnant, and regional
lymphatics should be included in most patients.
 Major nodal chains at risk include
lesser and greater curvature;
celiac axis;
pancreaticoduodenal,
splenic,
suprapancreatic,
porta hepatis groups;
para-aortics to the level of L3.
Any tumor originating in the stomach has a high propensity of spread to nodes
along the greater and lesser curvature, although they are most likely to spread to
those sites in close anatomic proximity to the primary tumor mass.

34. BORDERS
SUPERIOR BORDER- Bottom of T8 or T9 to
cover celiac axis, GE junction, fundus, and the
dome of left hemidiaphragm
INFERIOR BORDER- Bottom of L3 to cover
gastroduodenal nodes and antrum
LEFT BORDER- Include two third to three
Fourth of left hemidiaphragm to cover fundus,
suprapancreatic nodes and splenic nodes
RT LATERAL- 3 to 4 cm lateral to vertebral
Bodies to cover the antrum , porta hepatis,
and gastroduodenal nodes
Dose of RT- 45-50Gy/25#/5weeks, 1.8-2Gy/#

35. IVP 1 MIN IVP 3 MIN

36.  Position supine
 AP/PA parallel opposed fields
 Weighted equally or anteriorly more
to decrease spinal cord dose
 Blocks whenever possible should be
used to decrease dose to –
 Liver (70% <30Gy)
 Kidney (2/3 <20Gy)
 Heart (1/3 <45Gy)
IVP 10 MINS

38. CONTOURING OF CTV

41. LN INVOLVEMENT IN PROXIMAL THIRD STOMACH

43. LN INVOLVEMENT IN MIDDLE THIRD

45. LN INVOLVEMENT IN DISTAL THIRD

46. GASTRIC REMNANT
SPLENIC HILUM
PERIPANCREATIC
PORTA-HEPATIS

49. PRE OP RT
Series groups No of pts Survival
5 yr
LRR
Beijing Sx
Pre
RT(40)
199
171
20
30
52
39
Three other studies from Russia also evaluated role of adjuvant pre
op RT in potentially resectable patients.
All showed improved 3 yr and 5 yr survivals.
No increase in post opp c/cn
All trials used different doses of RT
Role for unresectable LAD evaluated in different studies show
survival benefit of 9-10 months

50. POST OP RT
Post op RT improves local control but does not improve survival unless combined
With chemotherapy

51. IORT
 Advantage
 Deliver a single, large fraction (10-35Gy) to tumour &
tumour bed
 Exclusion or protection of surrounding normal tissue
from the high-dose field.
Disadvantages
 Intense fibrosis.
 Neurological complications.
 Still a investigational tool.
 Yet to be proved better than conventional RT.
 Need special equipment and expertise.
Options- IORT+/-XRT

52. Linear accelerator with electron lucite
applicator

53. IDEAL INTEGRATION OF IORT AND EBRT

55. CHEMOTHERAPY
 Single agent therapy
 Combination therapy-
 Resectable d/s-
 Perioperative,
 Post operative.
 Locally advanced/metastatic d/s

56. SINGLE AGENT CCT
 The results - disappointing.
 CR in metastatic disease rare.
 PR – limited.
 Objective responses – limited & brief
duration
 Most widely used agents-
 5-fluorouracil
 Cisplatin
 Taxanes
 Single-agent therapy may be a reasonable
approach in patients who would not
tolerate, combination therapy.

57. COMBINATION CCT REGIMENS
 FAM
 5-FU 600 mg/M2 IV D- 1,8, 29,36
 Doxorubicin 30 mg/M2 IV D- 1,29
 Mitomycin C 10 mg/M2 IV D-1
 REF: MacDonald et al. Ann Intern Med 1980; 93:533-536
 Repeat every 56 days
 FAMTx
 Methotrexate 1500 mg/M2 IV D 1 give MTX first and then wait 1
hour and give 5-FU
 5-FU 1500 mg/M2 IV D- 1
 Leucovorin 15 mg/M2 PO Q6H D 2-4 X total 12 doses starting 24 hrs
after MTx
 Doxorubicin 30 mg/M2 IV D- 15
 REF: Kelsen et al. J Clin Oncol 1992; 10:541-548
 Repeat cycle on day 29

58.  ECF
 Epirubicin 50 mg/M2 IV D 1
 Cisplatin 60 mg/M2 IV D 1
 5-FU 200 mg/M2/d CIV(X21 days) daily
 REF: Webb et al. J Clin Oncol 1997; 15:261-267
Irinotecan/ cisplatin
 Irinotecan 70 mg/M2 IV days 1, 15
 Cisplatin 80 mg/M2 IV day 1
 REF: Boku et al. J Clin Oncol 1999; 17:319-323
 Repeat every 28 days

59.  PF paclitaxel/fluorouracil
 Paclitaxel 175 mg/M2 IV (over 3 h) day 1
 5-FU 1500 mg/M2 IV (over 3 h) day 2
 REF: Murad et al. Am J Clin Oncol 1999; 22:580-586
 Repeat every 21 days for a maximum of 7 cycles
 CF
 Cisplatin: 100 mg/m2 IV over 1–3 hrs D-1
 5-FU: 1,000 mg/m2/day IV cont infus D1–5
 Repeat cycle every 28 days
Docetaxel + Cisplatin
 Docetaxel: 85 mg/m2 IV D 1
 Cisplatin: 75 mg/m2 IV D 1
3 wkly repeated.
DCF
 Docetaxel: 75 mg/m2 IV D 1
 Cisplatin: 75 mg/m2 IV over 1–3 hrs D 1
 5-FU: 750 mg/m2/day IV cont infusion D 1–5
 Repeat cycle every 21 days.

60. ADJUVANT CCT
 Resectable
gastric ca
post sx
 Adjuvant
CT
• Significant DFS,
OS improvement
with hazard ratio
0.82
• 5% improvement
in 5 year survival.
• Conclusion: 5FU
based CT is
warranted.

61. PERIOPERATIVE CCT
 Perioperative CCT-
 British Med Research council Adjuvant Gastric Cancer
Infusional Chemo Trial (MAGIC)
NO. OF
PATIENTS
MEDIAN
SURVIVAL(
MONTH)
3 YEAR
SURVIVAL(
%)
5 YEAR
SURVIVAL(
%)
RFS (%)
ONLY
SURGERY
253 20 31 23 26
PERIOPERA
TIVE CCT
250 24 45 36 39

62. CONCURRENT CRT- PHASE II TRIALS
Study No Surv
median
Long% LRR No LRR %
MGH
Sx
RT+5-FU
110
14
-
24
38/5
43/5
46
2
42
14
TJUH
Sx
RT+CCT
70
20
12
19
13/5
21/5
17
3
45
19
Penn
Sx
SX+RT
Sx+RT+C
CT
40
17
27
16
15
21
31/2
50/2
55/2
31
4
4
75
24
15
Mayo
Rt + 5-
FU+_Le
25 19 31/4 5 20

63. INT-0116
 Agent Dosage
 5-FU 425 mg/M2 IV bolus days 1-5
 Leucovorin 20 mg/M2 IV bolus days 1-5
 1 cycle postop, followed by
 XRT–adjuvant
 5-FU 425 mg/M2 IV bolus days 1-4,38-40
 Leucovorin 20 mg/M2 IV bolus days 1-4,38-40
 concurrently with XRT
 CCT given on first 4 and last 3 days of RT followed by-
 POST RT
 5-FU 425 mg/M2 IV bolus days 1-5
 Leucovorin 20 mg/M2 IV bolus days 1-5
 every 28 days for 2 cycles

64. RESULTS

66. RESULTS

68. CALGB 80101
 Postoperative adjuvant chemoradiation for gastric
or GE junction adenocarcinoma using ECF before
and after 5-FU/radiotherapy compared to bolus 5-
FU/LV before and after 5-
FU/radiotherapy:Intergroup trial CALGB 80101
CS Fuchs, JE Tepper, D Niedzwiecki, D Hollis,
HJ Mamon, RS Swanson, DG Haller,
T Dragovich, SR Alberts, G Bjarnson, CG Willett,
PC Enzinger, RM Goldberg, AP Venook, RJ Mayer

69. CALGB 80101: Study Schema
R
A
N
D
O
M
I
Z
E
5-FU/LV
X1
ECF
X1
5-FU LVCI
RT
5-FU LVCI
RT
5-FU/LV
X2
ECF
X2
5-FU/LV: 5-FU 425 mg/m2 d1-5, LV 20 mg/m2 d1-5
RT: 45 Gy (1.8 Gy X 25 fractions) with 5-FU 200 mg/m2/d CI
ECF (pre-RT): Epirubicin 50 mg/m2 d1, Cisplatin 60 mg/m2 d1, &
5-FU 200 mg/m2/d CI d1-21
ECF (post-RT): Epirubicin 40 mg/m2 d1, Cisplatin 50 mg/m2 d1, &
5-FU 200 mg/m2/d CI d1-21

70. CALGB 80101
Overall Survival by Treatment Arm
Arm
Median
OS*
3-year OS 5-year OS
Hazard
Ratio
(95% CI)
5-FU/LV 36.6 mos 50% 41%
ECF 37.8 mos 52% 44%
1.03
(0.80-1.34)
*P, log rank = 0.80

71. UNRESECTABLE CARCINOMAS
 CRITERIA-
 Peritoneal involvement
 Distant mets
 Invasion/encasement of blood vessels
 Level 3 or 4 LN on imaging
 Palliative surgery- AIM-
 Palliate symptom
 least morbidity
 Least mortality
 INDICATIONS-
 Pyloric obstruction(GOO)
 Bleeding
 Pain
 OPTIONS-
 Distal gastrectomy,
 Total gastrectomy,
 Gastrojejunostomy,
 Intubations,
 Laser recanalization,

72. ROLE OF CRT IN UNRESECTABLE CARCINOMA

74. ROLE OF NEOADJUVANT CCT
 Potentially resectable LAD-
 EFP/EAP/FAMTX/CF- 15-16 m median survival with pCR only in 7-9
% in FAMTX pts of 60-70% resected.
 Boderline resectable LAD
 EAP/CF- 30/15 m median survival and only EAP regime showing 7%
pCR in 70% resected
 Unresectable LAD
 EAP/FMTX- 18 m survival with 44% resected and 15 % CR.
 So all phase II trials showing some significance and
none of 2 phase III trials showed any benefit.
In general, pathological complete response rate is low and
the impact of NACT on survival is even less.

75. METASTATIC DISEASE
SURGERY
 Palliative resection
 Endoluminal stenting
 Endoscopic laser treatment
 Gastrostomy tube placement
RADIATION
Radiation therapy is capable of providing substantial palliation of local gastric
cancer symptoms.
 50% to 75% of patients improve
 Indications-
 gastric outlet obstruction,
 pain from local tumor extension
 benefit may increase with concomitant 5FU administration,
 The median duration of palliation varies from 4 to 18 months in reports
addressing this issue
 Dose- PGI – 30gray/10#/2wks.

76. SINGLE AGENT
 Doxorubicin, mitomycinC, etoposide, cisplatin,5-FU- response rate of
20% or more
 Docetaxel- 23% response rate
 Irinotacan- 23% response rate
 Paclitaxel- 17-21% response rate
Complete remission is extremely rare and remission duration is 3-5
months.
COMBINATION CCT
 Reliable response in 25-50% of patients
 Median survival of 3-5 months
CCT

77. RESULTS
EORTC
RESPONSE RATE MEDIAN
SURVIVAL
FAM 41% 42 weeks
FAMTX 9% 29 weeks
ROYAL MARSADEN HOSPITAL
RESPONSE RATE SURVIVAL
FAMTX 21% 6 month
ECF 45% 9 month
1 year survival Median survival
EOX 46.8% 11.2 month
ECF 37.7% 9.9 month

78. TAXANE REGIMEN
PHASE II TRIAL
-Docetaxel plus cisplatin- response rate of 28-46% and median survival is 10.5 -11.4
month
PHASE III TRIAL
DCF CF
RESPONSE RATE 69% 59%
CCT OR BSC
- All the trials have showed better survival with CCT

79. ROLE OF TARGETED THERAPY
Patients with overexpression of HER2 by IHC or by FISH
Trastuzumab+
cis/5-FU
Cis/5-FU
MEDIAN OS 13.5 month 11.1 month

80. SEQUELAE OF THERAPY
 Anorexia, nausea, and fatigue -very common.
 Nutritional complications and myelo-suppression-especially in CRT
 Need careful nutritional support councelling and antiemetic therapy.
 Blood counts monitoring twice weekly during CRT to avoid sepsis or
bleeding.
 Achlorohydria –
 16 to 36 Gy reduce secretion of pepsin and HCL (25% to 40%) persisting 1 to 6 m,
with 25% upto 1 to 5 yrs or more.
 Gastric late effects categorized by the Walter Reed Group
 dyspepsia,
 radiation gastritis,
 uncomplicated gastric ulcer,
 gastric ulcer with perforation
 obstruction

81. TREATMENT ALGORITHM

82. TREATMENT ALGORITHM

84. 5 YEAR OS
 Stage IA- 71%
 Stage IB- 57%
 Stage IIA- 46%
 Stage IIB- 33%
 Stage IIIA- 20%
 Stage IIIB- 14%
 Stage IIIc- 9%
 Stage IV- 4%
(SEER 1991-2000)

85. CONCLUSION
 Endoscopy with direct visualisation, cytology and biopsy yields the
diagnosis in > 90% of patients.
 Locally advanced disease is the most common presentation.
 Only curative treatment is surgical resection of all gross and
microscopic disease.
 Even after curative gastrectomy, disease recurs in local or distant site or
both in the majority of patients.
 Efforts to improve these poor results have focused on developing pre
and postoperative systemic and local adjuvant therapies.
 Chemoradiation is the preferred adjuvant modality in patients with
stage IB, II, IIIA, IIIB or IIIc and M0 gastric cancer.
 In case of locally unresectable disease, combined modality therapy is
reasonable approach.