Gastric cancer remains the fourth most common cancer worldwide, with high rates in Eastern Asia and South America. While rates have declined significantly in the last century, most patients still present with advanced disease. Surgical resection with D1 or D2 lymphadenectomy offers the only chance for cure, with 5-year survival rates of 20-50% depending on stage. Adjuvant chemoradiation has been shown to improve survival after surgery in early stage disease. Ongoing studies continue to refine the use of neoadjuvant and adjuvant therapies to further improve outcomes.

1. Epidemiology
 Gastric cancer was the fourth most common cancer in the
world in 2004, and is expected to remain fourth in 2005.
 Worldwide there are 930,000 new cases and 700,000 deaths
per year. Sixty percent of new cases occur in developing
countries.
 There is tremendous geographic variation, with the highest
death rates in Chile, the former Soviet Union, China, and
Japan.

2. Epidemiology
 In the United States gastric cancer is the 15th most common
cancer, with 21,860 new cases expected this year, and
11,550 deaths.
 The incidence of gastric cancer has declined significantly
worldwide in the last century, with a marked decline in the
US since the 1930s.

5. Epidemiology
 In New York State there were an average of 1955 cases
annually between 1998-2002, with 1070 deaths.
 Male to female ratio of 2:1 in the US; 3:2 in New York.
 Median age at diagnosis is 65 years (40-70). Incidence
increases with age, peaking in the 7th decade.

6. Risk Factors
 Low fat or protein consumption
 Salted meat or fish
 High nitrate consumption
 High complex carbohydrate consumption

7. Risk Factors
 Environment
 Poor food preparation (smoked/salted)
 Lack of refridgeration
 Poor drinking water (well water)
 Smoking

8. Risk Factors
 Social
 Low social class (except in Japan)
 Medical
 Prior gastric surgery
 H. pylori infection
 Gastric atrophy and gastritis
 Adenomatous polyps
 Male gender

9. Risk Factors
 Helicobacter pylori
 Presence of IgG to H. pylori in a given population correlates
with local incidence and mortality from gastric cancer.
 Different strains elicit different antibody responses. The cagA
strain causes more mucosal inflammation and thus a higher
risk of gastric cancer than cagA-negative strains.

10. Risk Factors
 Adenomatous polyps
 10-20% risk of developing cancer, especially in lesions greater
than 2 cm.
 Multiple lesions increase the risk of developing cancer.
 Presence of polyps increase the chance of developing cancer in
the remainder of mucosa.
 Endoscopic surveillance is required after removal of polyps.

11. Decreasing Incidence
Improved nutrition and refrigeration of foods
Lower incidences of H. pylori due to increased
antibiotic use and cleaner water/sanitation leading
to decreased transmission of disease
Earlier detection and treatment in certain countries

12. Anatomy
 Most of the blood supply to the stomach is from the celiac
artery.
 Four main arteries:
 Left and right gastric along the lesser curvature
 Left and right gastroepiploic along the greater curvature.
 Blood supply to the proximal stomach also comes from the
inferior phrenic and short gastric arteries

13. Anatomy
 Occasionally (15-20%) an aberrant left hepatic artery arises
from the left gastric – a concern if the left gastric needs to
be divided.
 The extensive anastomotic connections between these
arteries allow, in most cases, three of the four vessels to be
ligated as long as the arcades between the curvatures are
not disturbed.

15. Anatomy
 Venous drainage parallels the arterial supply
 Left and right gastric veins drain into the portal vein
 Right gastroepiploic drains into the SMV
 Left gastroepiploic drains into the splenic vein

16. Anatomy
 Lymphatic drainage is into four zones:
 Superior gastric
 Suprapyloric
 Pancreaticolienal
 Inferior gastric/subpyloric
 All four drain into the celiac group of nodes and into the
thoracic duct.
 Gastric cancers drain into any of these groups regardless of
location of the tumor.

18. Anatomy
 Innervation:
 Parasympathetic via the vagus.
 Left anterior and right posterior.
 Sympathetic via the celiac plexus.

20. Anatomy
 Stomach has five layers:
 Mucosa
 Epithelium, lamina propria, and muscularis mucosae*
 Submucosa
 Smooth muscle layer
 Subserosa
 Serosa

22. Clinical Presentation
 Symptoms are often absent in early stages, and when
present are often ignored, missed, or mistaken for another
disease process.
 Vague discomfort and/or indigestion
 Epigastric pain that is constant, non-radiating, and unrelieved
by food ingestion.
 Proximal tumors may present with dysphagia.
 Antral tumors may present with outlet obstruction.

23. Clinical Presentation
 Diffuse mural disease may present with early satiety due to
decreased distensibility.
 Up to 15% of patients develop hematemesis and 40% are
anemic at presentation.

24. Clinical Presentation
 Unfortunately most patients present in later stages of
disease, with evidence of metastatic or locally advanced
tumor.
 Palpable abdominal mass, ovarian mass, supraclavicular or
periumbilical lymph nodes.
 Obstruction from tumor invasion into transverse colon.
 Hepatomegaly, jaundice, ascites, and cachexia.

25. Diagnosis
 Endoscopy is the diagnostic method of choice.
 With multiple biopsies (seven or more) the diagnostic accuracy
approaches 98%.
 Cytologic brushings can also be obtained.
 Size, morphology, and location of tumor can be documented,
as well as any other mucosal abnormalities.

26. Endoscopy

27. Endoscopy

28. Diagnosis
Double contrast
barium swallow has
90% accuracy and is
cost effective.
No ability to
distinguish between
malignant and benign
ulcers.

29. Diagnosis
 Endoscopic Ultrasound (EUS) is a newer modality that is
being used in some center to help stage the tumor.
 Extent of wall invasion and lymph node involvement can be
assessed.
 Overall accuracy is 75%.
 Poor for T2 tumors (38%)
 Better for T1 (80%) and T3 (90%)
 Remains operator dependent.

31. Preoperative Workup
 Once diagnosis of gastric cancer has been made, CT scan is
useful for evaluation of any distant disease.
 Limited in detecting early primary and small (<5mm)
metastatic tumors.
 Accuracy of lymph node staging ranges from 25 to 86%.
 If CT scan is negative, then laparoscopy is recommended as
the next step in evaluation.

32. Preoperative Workup
 Laparoscopy detected metastatic disease in 23 to 37% of
patients deemed eligible for curative resection by CT scan.
 Laparoscopy improves palliation in these patients by
avoiding unnecessary laparotomy in about one fourth of
patients presumed to have local disease on CT scan.

33. AJCC Cancer Staging Manual, Sixth Edition
Stomach
(Lymphomas, sarcomas, and carcinoid tumors are not included.)

35. AJCC Cancer Staging Manual, Sixth Edition
Stomach
(Lymphomas, sarcomas, and carcinoid tumors are not included.)

36. AJCC Cancer Staging Manual, Sixth Edition
Stomach
(Lymphomas, sarcomas, and carcinoid tumors are not included.)

38. Treatment
 Surgical resection remains the mainstay of
treatment and is the only curative option.
 More recently pre- and post-chemoradiation
therapy has been scrutinized to see if there is
any benefit to survival.
 The issue of extent of resection appears to have
been settled. As long as adequate tumor
margins are achieved, subtotal gastrectomy has
the same survival as total, with decreased
morbidity.

39. Neoadjuvant Therapy
 Radiation alone
 1970’s in Russia 152 patients were randomly assigned to
surgery alone or preop radiation with 20 Gy a week prior to
surgery. Five year survival rates were 30% and 39% respectively.
 In 1998 a Chinese group reported a prospective series of 370
patients who underwent surgery only or had 40 Gy preop
radiation. Five year survival was 19.8% vs 30.1% with radiation.
Resectability and radical resection rates were also improved.

40. Neoadjuvant Therapy
 Radiation alone
 In both studies reported perioperative mortality and
anastamotic leak rates were not significantly different.
 Further studies in radiation alone were largely abandoned in
favor of studies including chemotherapy.

41. Neoadjuvant Therapy

42. Neoadjuvant Therapy
 Chemotherapy alone
 A randomized Netherlands study (DGCT) was unable to show
any difference with preop chemotherapy. This may be in part
due to the regimen used – FAMTX (FU, doxyrubicin,
methotrexate).
 In the U.K. the MAGIC trial using ECF (epirubicin, cisplatin, FU)
has shown promising preliminary results, with 10% more
resectable cases and improved disease-free survival.

43. Neoadjuvant Therapy
 Combined chemoradiation therapy
 Has shown a beneficial impact on surgical outcomes in
esophageal and rectal cancers, making it an attractive
approach for gastric cancer as well.
 The M.D. Anderson Cancer Center reported several studies, one
in 2004 where patients who underwent preop
chemoradiotherapy – FU, leucovorin, cisplatin, and 45 Gy in 25
fractions over 5 weeks – achieved pathological complete and
partial response in 64% of all operated patients.

44. Neoadjuvant Therapy
 Chemoradiation therapy
 These patients showed a significantly longer median survival of
64 months in comparison to 13 months in patients who did not
reach complete or partial response.
 Further clinical trials are warranted to further show any benefit
of neoadjuvant chemoradiation.

45. Surgical Treatment
 Aggressive resection of gastric cancer is justified
in the absence of distant metastatic spread.
 The surgery is tailored mainly to the location of
the tumor and known pattern of spread.
 R0 resection should be achieved, with a
minimum of 6cm margins from gross tumor.
 R0 – tumor free margins
 R1 – microscopic disease
 R2 – gross tumor at margins
 Minimum of 15 nodes should be removed.

46. Surgical Treatment
 Tumors in the cardia and proximal stomach account for 35-
50% of gastric adenocarcinomas. For these tumors a total
gastrectomy should be performed, as opposed to proximal
gastric resection which is associated with higher morbidity
and mortality rates.
 Distal tumors may be removed by distal gastrectomy as
long as adequate margins are achieved.

47. Surgical Treatment
 The extent of lymphadenectomy remains
controversial.
 The JGCA classifies the lymph node basins into
16 basins, and are grouped according to the
location of the primary tumor as either D1, D2,
or D3 nodes. In general:
 D1 – removal of group 1 nodes along the lesser and
greater curvature.
 D2 – D1 plus group 2 nodes along the left gastric,
common hepatic, celiac, and splenic arteries.
 D3 – D2 plus para-aortic and distal lymph nodes

48. Lymph Node Stations

49. Surgical Treatment
 A 1993 survey by the ACS showed a 77.1%
resection rate in 18,365 patients, with a
postoperative mortality rate of 7.2% and 5-year
survival rate of 19%. Of these only 4.7% were D2
dissections.
 In comparison, the Japanese routinely perform
D2 dissections, with 5-year survival rates above
50%. Although earlier detection accounts for
much of the survival benefit, when comparing
cancers in the same stage, the Japanese continue
to have improved survival.

50. Survival Outcomes
0
20
40
60
80
100
120
Stage I Stage II Stage III Stage IV
US
Japan

51. Surgical Treatment
 Based on this and other retrospective data, four randomized
studies comparing D1 to D2 dissections have been
conducted.
 All four trials, including two large ones from the
Netherlands and Britain all show the same data; that D2
dissection significantly increases morbidity and mortality
without any significant increase in survival.

52. Surgical Treatment
 Splenectomy and pancreatectomy were found to be
important risk factors for morbidity and mortality after D2
dissection.
 In the DGCT trial a subgroup analysis of patients who
underwent D2 without splenectomy and/or pancreatectomy
had a significantly improved survival benefit.
 A randomized British trial also supported these findings in
stage II and III disease.

53. Surgical Treatment
 Based on these findings, many groups are recommending
“over-D1” lymphadenectomy for gastric cancers in Western
society.
 The large difference between the Japanese results and
Western results remains largely an enigma.

54. Surgical Treatment
 Choice of reanastamosis depends on extent of resection.
 Very distal gastrectomies may be reanastamosed via a
Billroth I, II, or Roux-en-Y.
 Subtotal gastrectomies will require a Billroth II or Roux-en-Y.
 Total gastrectomies are best served with a Roux-en-Y
anastamosis.

55. Surgical Treatment

56. Surgical Treatment

57. Surgical Treatment
 In the U.S. 20 to 30% of patients present with stage IV
disease.
 Palliative treatment should be geared toward relief of
symptoms with minimal morbidity, usually non-operative.
 Laser recanulization and endoscopic dilatation with or
without stent placement has shown success in relieving
outlet obstruction.

58. Adjuvant Therapy
 A 1999 review of the National Cancer Database reported
that only 29% of patients undergoing gastrectomy for
cancer had some form of adjuvant therapy.
 This shows the lack of convincing data up to that point that
adjuvant therapy increase survival in gastric cancer.

59. Adjuvant Therapy
 In 2001 the Southwest Oncology Group trial was published,
showing for the first time in a large prospective randomized
trial a survival benefit for patients undergoing gastrectomy
for cancer.
 Median survival was 27 months in the surgery only group,
and 36 months after chemoradiotherapy.

60. Adjuvant Therapy
 Survival was improved only in the D0 and D1 groups.
 Details on late toxicity have yet to be followed up on and
reported.
 Radiation toxicity had been improved with the use of IMRT
(intensity modulated RT), especially renal toxicity.

61. Adjuvant Therapy

62. Outcomes
 What can you expect?
 Patients who have undergone a potentially curative
resection have an average 5-year survival of 24 to 57%.
 More useful survival rates are stratified by stage of disease.

64. Outcomes
 Recurrence rates remain high, from 40 to 80% depending
on the series being quoted.
 Locoregional failure rate 38 to 45%, with most recurrence in
the gastric remnant at the anastamosis, gastric bed, and
lymph nodes.
 Surveillance is important. Patients should be followed every
4 months for the first year, then 6 months for 2 more years.
Yearly endoscopy should be performed for subtotal
gastrectomies.

65. Choice of Operation
 Open gastrectomy with lymph node dissection – at least D1
– is the current operative standard.
 Laparoscopic gastrectomy has been shown to be safe with
similar survival for patients with distal cancer.
 Learning curve needs to be overcome, which may be
difficult with the decreasing number of gastric cancer cases
in the U.S.