9. EPIDEMIOLOGY of Gastric Cancer
East Asia and South America
Most common cancer in JAPAN
M : F = 2 : 1
7th decade
JAPAN
10. THE MAGNITUDE OF PROBLEM
Male : Lung > Prostate > Colorectal > Stomach
4th most common cancer in men
Female : Breast > Cervix > Colorectal > Lung > Stomach
5th most common cancer in women
*2nd most commom cause of cancer death
*Poor prognosis
*India : Kashmir - 36/1,00,000
Chennai - 15/1,00,000
Bangalore - 10.6/1,00,000
ď§ Around 45-50% of gastric carcinoma present with an inoperable disease.
11. *RISK FACTORS
Nutritional
*Salted/smoked meat or fish (nitrate ď N-nitroso compounds)
*Low fresh fruits and vegetable (ascorbic acid)
*High complex carbohydrate consumption
*Low fat or protein consumption
12. Environmental
* Poor food preparation (smoked, salted)
* Lack of refrigeration
* Poor drinking water (e.g., contaminated well water)
* Smoking
Medical
* Prior gastric surgery (bile gastritis)
* H. pylori infection (not a/w tumors of cardia)
* Gastric atrophy and gastritis
13. Hereditary
* Hereditary diffuse gastric cancer (E-catherin â CDH1 gene)
80% lifetime incidence
prophylactic total gastrectomy
* Familial Adenomatous polyposis (APCgene, MUTYH gene)
10%-20% risk â size
Pedunculated- Endoscopic removal
Sessile and >2cm- excise
* Duodenal Polyps
* Li â Fraumeni syndrome / SBLA syndrome (p53)
* Lynch syndrome / HNPCC -hereditary nonpolyposis colorectal cancer (MLH1 or
MSH2 mutation)
Others
* Male gender
* Pernicious anaemia (achlorhydria)
* Proto oncogene overexpression â c-met , k-sam , c-erbB2
* Inactivation of tumor suppressor gene â p53 and p16
14. H.Pylori & Gastric carcinoma
⢠RESERVOIRS: human, primates, cats,
sheeps.
⢠Gram-negative spiral bacillus.
⢠Grows at pH: 4.5-9
⢠M/C site of colonisation - antrum
16. PPI and Gastric cancer
Impact of PPI on
incidence of
gastric cancer has
not been
elucidated.
....Sabiston
textbook of surgery 19th ed.
⢠PPI blocks H+-K+ pump
⢠Hypergastrinemia
⢠Hyperplasia of G-cells & ECL cells
⢠Carcinoid tumors in rats
In patients with H.pylori on long term
PPI, the low acid environment allows
bacteria to colonize the gastric body,
leading to corpus gastritis.
1/3rd develop atrophic gastritis.
(a risk factor for carcinoma)
18. Signet ring cell carcinoma (SRCC)
⢠Rare form of highly malignant adenocarcinoma
⢠Cells contain abundant mucin in the cytoplasm. So nucleus is shifted to periphery to
produce âsignet ringâ shape.
⢠Location â M/c in stomach; and less frequently in breast, gallbladder, urinary bladder,
and pancreas
⢠Contrary to others gastric cancer, the incidence of SRCC of the stomach is rising.
⢠SRCC tumors grow in characteristic sheets, which makes diagnosis using standard
imaging techniques, like CT and PET scans, less effective.
⢠Causes:
- inherited - mutations in CDH1 gene (cell-cell adhesion glycoprotein E-cadherin)
Once these cells lose E-cadherin, their motility increases
- APC gene mutation
⢠Prognosis
Early SRCC â better or atleast similar to than of non-SRCC
Advanced SRCC â poor than non-SRCC and lower chemosensitivity and peritoneal
carcinomatosis is the most frequent metastatic site.
A ring that killsâŚ.
20. ⢠Based on macroscopic apperance
⢠Useful as endoscopic finding
BORRMANN CLASSIFICATION
Protruded type
Depressed type
Type 1
Type 2
Type 3
Type 4
Type 5
Phymatoid/polypoid
Ulcerative
Infiltrative ulcerative
Diffuse infiltrative
Canât be classified
21. INTESTINAL type DIFFUSE type
Environmental Familial
Gastric atrophy, Intestinal
metaplasia
Blood type A
M > F F > M
Increasing incidence with age Younger age group
Gland formation Poorly differentiated
Hematogenous spread Transmural, lymphatic spread
Microsatellite instability
APC gene mutation
Decreased E-cadherin (CDH1 gene)
Inactivation of tumor suppressor genes p53, p16
Exophytic, bulky lesion Ulcerating lesion
Frequent intraperitoneal
metastasis.
LINITIS PLASTICA
LAUREN CLASSIFICATION
22. WHO Classification of Gastric Cancer
Classification based on morphologic features
ďź Adenocarcinoma â divided according to the growth
pattern in :
- papillary
- tubular
- mucinous
- signet ring
ďź Adenosquamous cell carcinoma
ďź Squamous cell carcinoma
ďź Undifferentiated
ďź Unclassified
23. *Clinical features
ďź Asymtomatic â 70%
Symptoms are nonspecific
advanced disease
at the time of diagnosis
*Epigastric pain
*Nausea and vomitting
*Early satiety
*Weight loss
27. *2011 consensus guidelines
advocate that patients ⼠55yr with new onset dyspepsia and
all those with alarm features
should have an urgent (within two weeks) gastroscopy
28. âAlarmâ features suggestive of
gastric cancer
*New onset dyspepsia in patients >55 years of age
*Family history of UGI cancer
*Unintentional weight loss
*Upper or lower GI bleeding
*Progressive dysphagia
*Iron deficiency anaemia
*Persistent vomiting
*Palpable mass
*Palpable lymph nodes
*Jaundice
30. 2 major staging systems for gastric carcinoma
ďą American Joint Committee on Cancer classification
ďą Japanese Classification of Gastric Carcinoma
Japanese classification uses T and M staging similar to the AJCC
system
Nodal staging is significantly different
⢠AJCC focuses on number of positive LN
⢠The Japanese classification focuses on anatomic location
of the nodes, which are designated by stations
31. T1a
T1b
Depth of tumor
invasion Number of involved LN
Presence or absence
of metastatic disease
TX â Primary tumor
canât be assessed
T0 â No evidence of
primary tumor
Tis- Carcinoma in situ
Mucosa
Submucosa
Muscularis
propria
Subserosal
CT
Serosa
T3 â gastro-
colic/hepatic lig.,
greater or lesser
omentum
32. RE GIONAL LYMPH NODES (N)
Based on number of LN involved and not the location
ďźIn 1997, nodal classification changed from using the location of the
involved lymph nodes to the number of lymph nodes
pN1, 1â6 nodes
pN2, 7â15 nodes
pN3, >15 nodes
-Requires a minimum of 15 nodes in the resection specimen
-Avrg no. of nodes evaluated - 10, only 30% of pts have at least 15
nodes evaluated
33. NX - Regional lymph node(s) cannot be assessed
N0 - No regional lymph node metastasis§
N1 - Metastasis in 1-2 regional lymph nodes
N2 - Metastasis in 3-6 regional lymph nodes
N3 - Metastasis in 7 or more regional lymph nodes
N3a - 7-15 nodes
N3b - 16 or more nodes
M0 - No distant metastasis
M1 - Distant metastasis
DISTANT METASTASIS (M)
Because of inadequate nodal evaluation
In the 7th edition of the AJCC classification, a minimum of 7
nodes are required.
35. Changes in the 7th edition of AJCC classification
GE junction tumors
or
tumors in the cardia <5cm from GE junction extending
into GE junction
Staged using the TNM staging for esophageal cancer
RĂźdiger et al. Ann Surg 2000; 232-353
36. *Nodal staging is significantly different
*Focuses on Anatomic location of the nodes, which are
designated by stations
*recommendes nodal basin dissection dependent on the location
of the primary
37. * No. 1 Right paracardial LN
* No. 2 Left paracardial LN
* No. 3 LN along the lesser curvature
* No. 4sa LN along the greater curvature â 4sa (short gastric vessels)
- 4sb (left gastroepiploic vessels)
- 4d (right gastroepiploic vessels)
* No. 5 Suprapyloric LN
* No. 6 Infrapyloric LN
* No. 7 LN along the left gastric artery
* No. 8 LN along the common hepatic artery - 8a(anterior group)
- 8p(posterior group)
* No. 9 LN along the celiac artery
* No. 10 LN at the splenic hilum
* No. 11 LN along the splenic artery â 11p proximal splenic
- 11d distal splenic
* No. 12 LN in the hepatoduodenal ligament â 12a (along the hepatic artery)
â 12b (along the bile duct)
â 12p (behind the portal vain)
* No. 13 LN on the posterior surface of the pancreatic head
* No. 14 LN along the superior mesenteric vessels â 14v superior mesenteric vein
- 14a superior mesenteric artery
* No. 15 LN along the middle colic vessels
* No. 16a1 LN in the aortic hiatus
* No. 16a2 LN around the abdominal aorta (from upper margin of celiac trunk to the lower margin of left renal vein)
* No. 16b1 LN around the abdominal aorta (from lower margin of left renal vein to the upper margin of inferior mesenteric artery)
* No. 16b2 LN around the abdominal aorta (from the upper margin of inferior mesenteric artery to aortic bifurcation)
39. Splenic
hilum
Proximal & distal
splenic
Hepatoduodenal ligament
-Hepatic artery
-Portal vein
-Bile duct
Posterior of
pancreatic
head
superior mesenteric vein
superior mesenteric artery
15
middle colic
artery and
vein
Mesentric
root
Transverse mesocolon
40. 16a1
aortic hiatus
16a2
16b1
16b2
Celiac trunk
Lt. renal vein
Inferior mesentric
artery
20
Esophageal hiatus
No. 17 anterior surface of pancreas
head
No. 18 inferior margin on the
pancreas
No. 19 Infradiaphragmatic LN
41. *Once the diagnosis is established, further studies are
directed at staging to assist with therapeutic decisions
*EUS and CT are primary radiological staging modalities
*Others â MRI, PET scan, laparoscopy
42. Endoscopy and Endoscopic Ultrasound
(stomach is filled with water)
(biopsy)
*T staging -
The gastric wall is visualized as 5 concentric bands:
Mucosa - Echogenic
Muscularis mucosa - Hypoechoic
Submucosa - Echogenic
Muscularis propria - Hypoechoic
Serosa - Echogenic
*N staging - presence and location of peri-visceral lymph nodes or
detection of malignant cells by EUS guided trans-visceral FNA
*Less useful for M staging, due to limited depth of penetration
However, with low frequency newer echo-endoscopes, much of the liver can be surveyed and sampled
from the stomach and duodenum
In the future, EUS may play a role in determining those patients who require further
aggressive investigation of metastatic disease (e.g., laparoscopy) and those who do not.
gastric tumor -
hypoechoic mass
43. Computed Tomography
*useful for M staging
- primary method for detection of intra-abdominal metastatic disease,
with an overall detection rate of approximately 85%.
For detecting SENSITIVITY SPECIFICITY
Liver metastasis 75% 99%
Peritoneal
metastasis
33% 95%
44. T staging and N staging â
ď§The accuracy of T and N stages as determined by CT is less accurate
than EUS. Sabiston textbook of surgery 19th ed.
* Accuracy for T staging - 64%
Paramo JC et al. Ann Surg Oncol1999;6:379-84
* Sensitivity for N staging â 50 to 95%
Irving, recent advances in surgery.
ď§ CT and MRI are not useful in distinguishing between enlarged nodes
due to reactive changes and those due to tumor.
45. MRI
When CT iodinated contrast is contraindicated
* For T staging, MR is comparable or minimally superior to CT
Sohn KM et al. AJR Am J Roentgenol 2000;174:1551-7
* Inferior to CT in N staging
* M staging - Improvement in detection of metastatic disease
compared with CT, when the contrast Ferumoxtran-10 is used
(sensitivity 100%)
Coburn NG. J Surg Oncol 2009;99(4):199â206
Motohara T, Semelka RC. Abdom Imaging 2002;27(4):376â83
46. PET scan
*not currently a primary staging modality.
*Only 50% gastric cancers are PET-avid
*PET response to neoadjuvant therapy seen after 14 days of
treatment strongly correlates with survival, therefore for
monitoring response to these therapies, sparing unresponsive
patients further toxic treatment
47. Staging Laparoscopy
In 1985, report by Shandall and Johnson
Detection of metastatic disease to the liver or peritoneum
* Sensitivity - 100%, specificity - 84%
*Avoidance of laparotomies - 29% of pts
Now N staging is possible with laparoscopic ultrasound
Implications
*In resectable pts. for staging
*In unresectable pts. â determination of benefits of combined chemo-
radiation (radiation may not be appropriate in metastatic disease)
Jaffer A et al. http://www.nccn.org, v.1.2006
*Staging before entry into neo-adjuvant trials
DâUgo DM et al. J Am Coll Surg 2003;196:965-74
Not necessary in T1 or T2 lesions given the low incidence of metastases.
48. CT scanning and endoscopic ultrasonography (EUS) are complementary.
CT scanning is used first to stage the gastric carcinoma; if no metastases and
no invasion of local organs are found, EUS is used to refine the local stage.
The depth of tumor invasion is not accurately assessed with CT, and the
investigation of choice for this indication is EUS.
Unlike CT and MRI, EUS can depict individual layers of the gastric wall, with
a rotating high-frequency probe
49. SURGICAL THERAPY â the only prospective of cure
Objective : Complete resection of gastric tumor with a wide (âĽ6cm) margin
what is R status ?
Describes tumor status after resection
⢠R0 â microscopically margin-negative resection.
⢠R1 â macroscopic clearance of tumour but microscopic margins are positive.
⢠R2 â gross residual disease.
âŚHermanek, 1994
50. Total gastrectomy should not as a routine procedure for gastric
adenocarcinoma.
Patients in whom R0 resection can be obtained, a more limited gastric
resection (e.g., proximal esophagogastrectomy or distal subtotal gastrectomy)
provides the same survival result less perioperative morbidity.
Surgery
Endoscopic
sub-
mucosal
resection
Hemi-
gastrectomy
Subtotal
gastrectomy
Total
gastrectomy
51. EMR and ESR
EMR (Endoscopic mucosal resection)
injection of a substance under the targeted lesion to act as a cushion,
lesion is then removed with a snare or suctioned into a cap and snared
.
ESR (Endoscopic sub-mucosal resection)
injection of a substance under the targeted lesion to act as a cushion,
submucosa is instead dissected under the lesion with a specialized knife.
This enables removal of larger and potentially deeper lesions
ď higher rates of R0 resections and a lower rate of local recurrence, but
ď technically demanding and has more adverse events.
52. Disadvantage
Incomplete resection d/t large tumor size or unrecognised LN metastasis
A Japanese study
N = 5000
⢠small tumors, regardless of ulcer status, and
⢠nonulcerated tumors, regardless of size,
did not have associated lymph node disease.
patients with submucosal invasion less than 500 Îźm behaved similarly to
patients who had completely intramucosal
tumors.
Guidelines for ESR
ď§ All intramucosal tumors (any size) without ulceration
ď§ Differentiated mucosal tumors of <3cm, with/without ulceration
ď§ Limited submucosal invasion with size <3cm & without ulceration
56. Extent of nodal dissection D1 v/s D2
most controversial area in gastric cancer management
Non japanese literature
D2 lymphadenectomy, when compared with a D1 dissection, has increased surgical
morbidity, without a benefit in survival.
One criticism of the Western data is that although randomized, the D2 group did not
differentiate between patients who had a splenectomy and those who did not.
Subsequent subgroup analysis of the D2 without splenectomy group has shown
results similar to the Japanese studies, with increased survival and no significant
increase in morbidity.
Japanese literature
Increased survival in patients undergoing a D2 dissection, with no increased or
minimal increase in morbidity.
57. Resectable or not ?
ď§ Involvement of other organ per se does not imply incurability, provided that it
can be removed âŚ.Bailey and loveâs short practice of surgery 26th ed.
ď§ Therapeutic nihilism should be avoided &, in low risk patient, an aggressive
attempt to resect all tumor should be made. The primary tumor may be resected en
bloc with adjacent involved organs (eg., pancreas, transverse colon, or spleen)
âŚâŚSchwartzâPrincilpes of Surgery 10th ed.
ď§ A solitary metastatic nodule in liver is also no indication against curable
resection.
..(CSDT) Current Diadnosis and Treatment, Surgery 14th ed.
58. Steps in Total gastrectomy
Long mid-line incision or b/l subcostal incision (chevron)
Detachment of greater omentum from
colon
anterior layer of mesocolon is dissected
from mesocolonic vessels
Dissect upto inferior border of
pancreas and divide Rt GE vessels
Dissect upto splenic hilum, ligate Lt.
GE & short gastric
dissect lesser omentum
from the undersurface
of the Liver extending
back to the right crus
and mobilizing the right
aspect of G-E junction.
Divide duodenum with GIA stapler
59. close the duodenal stump with
interrupted horizontal 3-0 absorbable
mattress sutures, essentially
"dunkingâ the duodenum.
Dissection of porta, hepatic artery, &
celiac axis is completed from above
down
Left gastric artery divided at its
origin f/b clearance of right crus
and celiac axis
dissection of all the tissue from
Lt. crus & paracardial LNs
Mobilization of esophageal
hiatus by detaching the
peritoneal reflection from
the diaphragm
Divide esophogus sharply by knife
or scissors
60. Steps in Subotal gastrectomy
1) Mobilization of the greater curvature
with omentectomy & division of left
gastroepiploic vessels
2) lnfrapyloric mobilization with
ligation of the right gastroepiploic
vessels
3) Suprapyloric mobilization with
ligation of the right gastric vessels
4) Duodenal transection
5) D2 lymphadenectomy, with
dissection of the porta hepatis,
common hepatic artery, left gastric
artery, celiac axis, & splenic artery,
and ligation of left gastric vessels
6) Gastric transection
61. Peri-operative Chemotherapy
ďą MAGIC trial
Randomised controlled study of 503 pts. With stage II or higher gastric cancer that
compared perioperative chemotherapy with surgery alone.
CEF (Cisplatin, Epirubicin, 5-FU) - 3 cycles as neo-adjuvent CT
- 3 cycles as adjuvent CT
5-yr survival, rate of local recurrence & distant metastasis were improved in CT
group
ďą UK National Cancer Institute trial
OEX (Oxaliplatin, Epirubicin, Capecitabine)
longer overall survival than with CEF and decreased incidence of thromboembolic
phenomenon by substituting oxaliplatin for cisplatin
62. Intraperitoneal Chemotherapy (IPC)
ď§ Recurrence following curative resection is likely due to peritoneal
carcinomatosis.
ď§ Systemic CT : blood-peritoneal barrier prevents the chemotherapeutic agents
from achieving their cytotoxic effect.
ď§ IPC : administering high doses of chemotherapy directly to the peritoneum
whilst reducing the systemic effects.
ď§ HIPC (hypothermia Intraperitoneal Chemotherapy )
ď increased risk of neutropaenia and intra-abdominal abscesses.
63. Adjuvent Radiotherapy
INT(0116) trial demonstrates improvement in DFS and OS with post-operative
chemoradiation than with surgery alone.
Radiotherapy is limited, due to its position near vital organs like kidney spinal cord,
pancreas, liver & bowel.
Stomach itself is highly sensitive, tends to bleed and ulcerate with EBRT.
Intraoperative radiotherapy (IORT)
Takahashi & Abe in 1986, Japan randomized 211 patient IORT (25- 40 Gy) Vs
surgery alone claims â in 5-yr SR with IORT.
Chen & Song 1994, China randomized stage 3 & 4 patients for surgery with IORT
Vs surgery alone claims â in SR only in stage 3.
Sindelar & Tepper et al in 1993 , NCI (National Cancer institute) claims no survival
benefit with IORT, but improvement in local recurrence (44% Vs 92%, p < 0.001).
Still it needs to define the role of IORT in gastric carcinoma.
64. Reconstruction after surgery
After total gastrectomy ď¨Roux-en-Y esophago-jejunostomy
Division of jejunum with GIA
stapler
end-to-side esopago-
jejunostomy
65. full-thickness running
suture
Placement of the
EEA stapler through
the divided loop
Completion of the stapled anastomosis
and closure of the end of the loop with
a stapler.
ď§ Jejunal loop should be at least 40 cm from the subsequent jejunojejunal anastomosis to
minimize esophageal reflux.
66. Alternative reconstruction with
the EEA stapler using a separate
enrerotomy and end-to-end
anastamosis
Jejunal pouch / Omega pouch
Pouch creation can be done safely without increased
morbidity or mortality without significantly increasing the
operative time.
QOL was significantly better in pts with pouch
reconstruction.
Gertler R et al. Am J Gastroenterol 2009; 104(11):2838â51
make the pouch first by two passages of the GIA
stapler and then perform the Esophago-jejunal
anastomosis
67. Completed Roux-en-Y reconstruction
Post-op :
Unless fever or ileus develops, the patient is
allowed ice on the 1st day and can be given
nutrient by the 5th day.
Any concern clinically for anastomotic leak can
be confirmed by a Gastrografin Swallow, which
is not routine
68. After Subtotal gastrectomy ď Loop gastro-jejunostomy (Bilroth II) or
Roux-en-Y gastrojejunostomy
Stomach divided at greater curvature for 6-8 cm by knife (site of future
anastamosis) and then completely divided with GIA stapler
Staple line inverted with
suture
Anticolic Bilroth II
Retrocolic Bilroth II
Bilroth II
69. Standard technique for a two-layer, hand-sewn gastrojejunal anastomosis
After placement of corner
sutures, a back row of interrupted
3-0 silk Lembert sutures is
placed
jejunostomy is made with
cautery
inner layer anastomosis
is constructed in running, full-
thickness fashion with 3-0 PDS
Anterior
row of
interrupted
3-0 silk
Lembert
sutures
70. After Subtotal gastrectomy ď Roux-en-Y gastrojejunostomy
jejunum is divided with GIA
stapler approx. 20cm distal to
the ligament of Treitz
end-to-side Roux-en-Y
gastrojejunostomy is created
with a Roux limb at least
45cm in length to avoid
reflux
71. Laparoscopic resection
Meta-analysis of 5 randomized trials and 18 non ârandomized comparisons of
laparoscopic versus open gastrectomy came to following conclusions
ď§ Mean number of lymph nodes retrieved by laparoscopic surgery was
close to that retrieved by open procedure
ď§ Less blood loss
ď§ Lengthier operative times
ď§ Conversion rate â 0 â 3%
ď§ Significantly less postoperative morbidity after a laparoscopic procedure
ď§ No difference in long term survival
Tanimura S et al. Surg Endosc 2008; 22(5):1161â4.
Kawamura H et al. World J Surg 2008;32(11):2366â70
Revised Japanese Gastric Cancer Treatment Guidelines
Laparoscopy-assisted gastrectomy eligible for - stage IA and IB (T1N1,
T2N0) cancers.
Kodera Y et al. J Am Coll Surg 2010; 211(5):677â86
72. Robot assisted Surgery
Robot assisted surgery (RAS)
Advantages
⢠Provides articulated movement
⢠Eliminates physiologic tremor
⢠Steady camera platform allows more precise instrument
movement and dissections
Song J et al. Ann Surg 2009;249(6):927â32
73. Palliative therapy
Palliative surgery
- Intention
To relieve pain and suffering without increasing morbidity or mortality
- Numerous palliative procedures
⢠Gastro-enterostomy (enteric bypass)
Palliation â infrequent
19% felt they benefited
Peri-operative mortality â high âŚ.ReMine WH. World J Surg 1979;3:721-9
⢠Partial gastrectomy
⢠Total gastrectomy
59% felt improved their QOL âŚ.Monson JR et al. Cancer 1991;68:1863-8
⢠Esophago-gastrectomy
⢠Jejunostomy - for nutritional supplementation
⢠acute refractory hemorrhage - Endoscopic techniques (laser argon ablation,
epinephrine injection) and arterial embolization
⢠GOO â endoscopic dilation and stent placement (short term), CT, bypass with
gastrojejunostomy
74. Palliative Chemotherapy
ď§ CEF - Improve survival in patients with unresectable tumor
Adverse reactions are common, with up to 50% of patients having severe
neutropenia or GI complaints.
ďź Cetuximab â epidermal growth factor receptor (EGFR) inhibitor
ďź Trastuzumab (Herceptin) â human EGFR2 (HER2) antagonist
better median survival and overall response rate than CEF
75. One should remember
1) 6 cm margin clearance of tumour is recommended.
2) D2 lymphadenectomy is essential.
3) Resection of greater & lesser omentum is necessary.
4) Splenopancreatectomy only on indicated cases.
5) For proximal lesion varying length of esophagus should be
excised.
6) Judicious decision should be taken for total, proximal & distal
gastrectomy.
7) All patient should receive chemoradiation.