1. 胃 癌 Gastric Cancer 浙江大学医学院附属第一医院 胃肠外科 于吉人 Ji-Ren Yu
Zhejiang University
胃 癌
Gastric Cancer
浙江大学医学院附属第一医院
胃肠外科 于吉人
Ji-Ren Yu
Department of GI Surgery
The First Affiliated Hospital
College of Medicine, Zhejiang University

2. Gastric Cancer Epidemiology
Zhejiang University
Gastric Cancer
Epidemiology
i) One of the most common cancer worldwide is surpassed only by lung cancer as the leading cause of cancer deaths;
ii) higher rates in Eastern Asia, South America, Eastern Europe;
Gastric carcinoma is one of the most common cancer worldwide ,which is surpassed only by lung cancer as the leading cause of cancer deaths. The incidence of gastric carcinoma is high in Eastern Asia, South America, Eastern Europe, and is low in Western Europe and the United States.
iii) lower rates in Western Europe and the United States. 2

3. Epidemiology Incidence per 100,000
Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006;12(3):
Correa P Cancer Epidemiol Biomarkers Prev 2003;12:238s-241s

4. Gastric Cancer Risk Factors i) Nutrition
Zhejiang University
Risk Factors
i) Nutrition
A diet high in salty and smoked foods A diet low in fruits and vegetables Eating foods contaminated with aflatoxin fungus
ii) Environment and Heredity
Smoking
Family history of stomach cancer
Male
Most epidemiologic studies investigating the role of diet in relation to the development of gastric cancer associate diets low in animal protein and fat, high in complex carbohydrates, high in salted meats and fish, and with high levels of nitrates or H. pylori in drinking water with an increased risk for gastric cancer. It appears that the long-term ingestion of nitrates in dried, smoked, salted food and cigarette smoking contributes to this increased risk. 4

5. Gastric Cancer Risk Factors iv) Medical iii) Social
Zhejiang University
Risk Factors
iii) Social
Low social class
iv) Medical
Prior gastric surgery Helicobacter pylori infection Gastric atrophy and gastritis Adenomatous polyps
Pernicious anemia
Other factors associated with an increased risk for gastric cancer include low socioeconomic status, male gender, and H. pylori infection. 5

6. Etiological Factors (Risk Factors)
Etiological factors are presented in this figure. 6

7. A Model for the Pathogenesis of the Gastric Cancer
A model of the pathogenesis of human gastric adenocarcinoma shows that Human gastric carcinogenesis is a multistep and multifactoral process 7

8. i) Early gastric cancer(EGC)
Pathology
Zhejiang University
i) Early gastric cancer(EGC)
Gastric cancer confined to the mucosa or submucosa, regardless of the presence or absence of lymph node metastasis
ii) Advanced gastric cancer(AGC)
Cancer cells infiltrate the proprial muscle layer or serosa

9. Pathology EGC IIc: superficially depressed I: protruded III: excavated
The are Five types of early gastric cancinoma:type I: protruded type,type Iia :superficially elevated type,type IIb:superficially flat type ,type IIc: superficially depressed types and type III: excavated type.
III: excavated
IIa: superficially elevated
IIb: superficially flat 9

10. EGC:Endoscopic images
Endoscopic images of different types early gastric carcinoma.
Type I
Type II
Type III 10

11. Pathology AGC: Borrmann’s classification Linitis plastica
Normally, the Borrmann system divides gastric carcinoma into four types depending on the lesion's macroscopic appearance. Borrmann type 1 represents polypoid or fungating lesions; type 2, ulcerating lesions surrounded by elevated borders; type 3, ulcerating lesions with infiltration into the gastric wall and type 4, diffusely infiltrating lesions.
Linitis plastica
Borrmann's pathologic classification of gastric cancer based on gross appearance 11

12. T stage are defined by depth of penetration into the gastric wall
Lamina
propria
T1a
T1b
T4a
T4b T3
Subserosal connective tissue
T stage are defined by depth of penetration into the gastrci wall, T1:Tumor invades lamina propria or submucosa, T2:Tumor invades muscularis propria or subserosa,T3: Tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures; T4: Tumor invades adjacent structures. 12

15. Staging
N stage
This picture shows the grouping of regional lymph nodes by location of primary tumor according to the Japanese classification of gastric carcinoma.
Grouping of Regional Lymph Nodes (Groups 1-3) by Location of Primary Tumor According to the Japanese Classification of Gastric Carcinoma 15

16. M, lymph nodes regarded as distant metastasis
LOCATION OF PRIMARY TUMOR IN STOMACH
LYMPH NODE STATION (NO.)
DESCRIPTION
Upper Third
Middle Third
Lower Third 1
Right paracardial 2
Left paracardial 3 M
Lesser curvature
4sa
Short gastric
4sb
Left gastroepiploic 4d
Right gastroepiploic 5
Suprapyloric 6
Infrapyloric 7
Left gastric artery 8a
Anterior comm. hepatic 8p
Posterior comm. hepatic 9
Celiac artery 10
Splenic hilum
11p
Proximal splenic
11d
Distal splenic
12a
Left hepatoduodenal
12b,p
Posterior hepatoduodenal 13
Retropancreatic
14v
Superior mesenteric vein
14a
Superior mesenteric artery 15
Middle colic
16al
Aortic hiatus
16a2,b1
Para-aortic, middle
16b2
Para-aortic, caudal
Lymph node stations are defined by the Japanese classification of gastric carcinoma.
M, lymph nodes regarded as distant metastasis 16

17. Metastesis Direct invasion Lyphmatic metastesis
Hematogenous metastasis
Seeding metastasis
Gastric carcinoma can spread to other organs via at least 4 different routines, which are direct invasion ,lyphmatic metastesis,hematogenous metastasis and seeding metastasis. 17

18. Clinical Presentation
Lacks specific symptoms early: vague epigastric discomfort indigestion.
Epigastric pain is constant, nonradiating, and unrelieved by food ingestion.
Advanced disease may present with weight loss, anorexia, fatigue, or vomiting.
Symptoms often reflect the site of origin of the tumor. Proximal tumors involving the gastroesophageal junction often present with dysphagia, whereas distal antral tumors may present as gastric outlet obstruction.
Hematemesis, anemic.
Very large tumors erode into the transverse colon, presenting as large bowel obstruction.
Gastric cancer lacks specific symptoms at early period. Advanced disease may present with epigastric pain,weight loss, hematemesis.Very large tumors erode into the transverse colon,presenting as large bowel obstruction. 18

19. Physical signs i) a palpable abdominal mass,
ii) a palpable supraclavicular (Virchow's) or periumbilical (Sister Mary Joseph's) lymph node,
ii) peritoneal metastasis palpable by rectal examination (Blummer's shelf),
iii) a palpable ovarian mass (Krukenberg's tumor).
iv) as the disease progresses, patients may develop hepatomegaly secondary to metastasis, jaundice, ascites, and cachexia.
Physical signs develop late in the course of the disease and are most commonly associated with locally advanced or metastatic disease. Patients may present with a palpable abdominal mass, a palpable supraclavicular (Virchow's) or periumbilical (Sister Mary Joseph's) lymph node, peritoneal metastasis palpable by rectal examination (Blummer's shelf), or a palpable ovarian mass (Krukenberg's tumor). As the disease progresses, patients may develop hepatomegaly secondary to metastasis, jaundice, ascites, and cachexia. 19

20. Examination Endoscopy M－SCT (multiple detector-row spiral CT)
BUS & EUS
double-contrast radiography
MRI
DL (diagnostic laparoscopy )
PET-CT

21. Clinicpathological Staging
Laprascopy
BUS CT
EUS
MRI
PET-CT
CT is the mainly procedure

22. Endoscopy Carcinoma in situ Advanced carcinoma
When gastric cancer is suspected based on history and physical examination, flexible upper endoscopy is the diagnostic modality of choice
Carcinoma in situ
Advanced carcinoma 22

23. Double-Contrast Barium Upper GI Radiography
Niche
A Niche can be shown by double-contrast barium upper GI radiography in ulcerating tumor. 23

24. EUS EUS can detect the tumor infilltrated layer of the gastric wall.24

25. EUS T N
EUS aslo can detect the enlarged perigastric lymph nodes. 25

26. CT scan
Borrmann I

27. CT Scan A B C T N H1
T4N2M1

28. PET-CT: T3N2

29. BUS left right Liver metastasis Krukenberg’s tumor
Krukenberg‘s tumor and live metastasis are detected by peroperative B ultrasonograph.
Liver metastasis
Krukenberg’s tumor 29

30. Laparoscopy T T Abdominal metastasis
Diagnostic laparoscopy detected metastases on the peritoneum and round ligaments of liver T
Abdominal metastasis 30

31. Treatment for Gastric Cancer
Surgery
Endoscopic mucosal resection (EMR)
Endoscopic submucosal dissection (ESD)
Laparoscopic Surgery
Open Surgery
Chemotherapy
Chemoradiotherapy
Target therapy
et,al

32. EMR for Earlier gastric cancer (EGC )
EMR represents a major advance in minimally invasive surgery for gastric carcinoma. Indicators for EMR include well-differentiated or moderately differentiated histology,tumors less than 30mm in size,absence of ulceration and no evidence of invasive findings. 32

33. Criteria for EMR NCCN 2011 V1. Japanese Gastric Cancer Association
1.Early gastric cancer (Tis or T1a tumors limited to mucosa)
2. Well-differentiated or moderately differentiated histology
3.Tumors less than 20mm in size,
4.Absence of ulceration and no evidence of invasive finding.
Japanese Gastric Cancer Association
( Digestive Endoscopy. 2005,17, 54–58)
differentiated adenocarcinoma;
Intramucosal cancer;
20 mm in size;
without ulcer finding
EMR represents a major advance in minimally invasive surgery for gastric carcinoma. Indicators for EMR include well-differentiated or moderately differentiated histology,tumors less than 30mm in size,absence of ulceration and no evidence of invasive findings. 33

34. EMR

35. EMR

36. EMR

37. Limitation of EMR techniques
1. Difficult to resect large than 20mm tumor in size
2. Difficult to resect ulcerative lesions
ESD has been developed

38. ESD for EGC
EMR represents a major advance in minimally invasive surgery for gastric carcinoma. Indicators for EMR include well-differentiated or moderately differentiated histology,tumors less than 30mm in size,absence of ulceration and no evidence of invasive findings. 38

39. ESD
Oita Digestive Organs Hospital

40. ESD
Oita Digestive Organs Hospital

41. Criteria for ESD National Cancer Center Hospital In Japan
(evaluation for histological curability)
(indication for DST)

42. Surgical Treatment for Gastric Cancer
Principles of radical operation for gastric cancer
i) Negative margin (adequate margins ≥4 cm )
ii) D2 lymph node dissection for advance gastric cancer
iii) Subtotal gastrectomy for distal gastric cancer
iv)Total or proximal gastrectomy for proixmal gastric cancer
Surgery is the only procedure to cure gastric cancer. The goal of a surgical cure requires complete resection to an R0 status, which approach to surgery is determined by 1) the negative margin, 2)the extent of lymph node dissection needed,3)the enbloc resection needed and 4) no distant metastasis. 42

43. Laparoscopic Resection
A suitable procedure for ECG (Our experience)
The efficacy and safety of this approach for advanc gastric carcinoma requires further investigation to be evaluated
The efficacy and safety of laparoscopic resection need requires further investigation in larger randomized clinical trials. At present, laparoscopic resection is a suitable procedure for early gastric carcinoma. 43

44. Open Surgery for Advanced Gastric Cancer
A suitable procedure for ACG
R0 resection
R1 resection
R2 resection

45. Principles of advanced gastric cancer surgery
Gastrectomy with regional lymphatics: perigastric lymph nodes(D1) and those along the named vessels of the celiac axis (D2), with a goal of examining 15 or greater lymph nodes
Gastrectomy with D2 lymphadenectomy is the standard treatment for curable GC in eastern Asia

46. Gastrectomy and D2 lymphadenectomy for advanced gastric carcinoma
For advance gastric carcinoma, open surgical resection are recommended. 46

47. The standard of surgical procedure varies worldwide, with most Asian countries encouraging extended lymphadenectomy. The majority of surgeons in the USA, on the other hand, excise the N1 lymph nodes, which are in the immediate perigastric region. This resection is called a D1 resection. A D2 resection, as described in the 2002 American Joint Committee on Cancer manual, includes nodes along the celiac access and its named branches and along the middle colic, superior mesenteric artery, and periaortic nodes. 47

48. Gastric resections are determined by tumor location
Gastric resections are determined by tumor location. Reconstruction can be performed using a Billroth II or Roux-en-Y anastomosis. Distal gastrectomies are often done for distal tumors. A Roux-en-Y anastomosis tends to eliminate troublesome bile reflux. 48

49. Body and midstomach tumors typically require a total resection to gain adequate margins of at least 6 cm. 49

50. Left gastric A
Hepatic A
Splenic A
No.11 LN

51. PORTAL VEIN

52. Tumor located at the midstomach which has invased into the spleen
Tumor located at the midstomach which has invased into the spleen. Total gastrectomy in combination with splenoectomy was done. 52

55. Viedo of operation Ligaments of liver and stomach disection
Right gastric arteries disection
Right gastroepiploic arteries disection
Ligaments of spleen-stomach disection
esophagus disection
N7,N8,N9 disection
N7,N8,N9 disection
N12，N13 disection

56. Adjuvant Therapy Chemotherapy Radiation Therapy Targeted Therapy
Adjuvant therapy to potentially curative surgery in patients with locally advanced gastric cancer can contribute to the elimination of micrometastatic and increased survival. But substantial room for further improvement of outcomes are still remained.Adjuvant therapies to gastric cancer include Neoadjuvant chemotherapy, postoperative chemotherapy and postoperative chemoradiation. 56

57. Chemotherapy …… Regimens ECF: Epirubicin , Cisplatin,
SOX: S-1, Oxaliplatin
XELOX: Capecitabin, Oxaliplatin
DCF: Docetaxel, Cisplatin, 5-Fu ……
Preoperative Chemotherapy
Postoperative Chemotherapy

58. Preoperative chemotherapy
Our experience
Before the neoadjvant chemotherapy
Ulcerative mass at antrum of stomach，about 4*5cm in size
After 3 courses FOLFOX6
The lesion is about 2.0*1.0cm in size

59. Our experience
Before the neoadjvant chemotherapy
After 3 courses of XELOX

60. Lymphadectomy of group 7,8,9
Our experience
Lymphadectomy of group 7,8,9

61. Liver after Chemotherapy
Our experience
Liver after Chemotherapy

62. Our experience
foam cells in lamina propria(40×10)

63. Targeted Therapy
Herccptin Herb-2 receptor inhibitor
Iressa EGFR inhibitor
Avastin VEGFR inhibitor

64. Other Molecular Medicine Interventions of Gastric Cancer
1.Oncogene activation and targeted therapy
2.Tumor-suppressor-gene inactivation and related therapy
3. Apoptosis targeted therapy
4. Anti-metastasis therapy
5. Telomerase inhibition therapy
6. Gene directed chemotherapy
7. Immunotherapy

65. Palliative Treatment Surgical palliation
resection or bypass alone or in conjunction with percutaneous, endoscopic, or radiotherapy techniques
Nonoperative therapies
laser recannulization and endoscopic dilation with or without stent placement
Because 20% to 30% of gastric cancer patients present with stageIII or IV disease, clinicians must be familiar with different methods of palliative treatment. The goal of palliative treatment is the relief of symptoms with minimal morbidity. Surgical palliation of advanced gastric cancer may include resection or bypass alone or in conjunction with percutaneous, endoscopic, or radiotherapy techniques. Complete staging is necessary to determine the appropriate method of palliation for individual patients. In the presence of peritoneal disease, hepatic metastases, diffuse nodal metastases, or ascites, palliation of bleeding or proximal gastric obstruction would preferably be obtained nonoperatively. Nonoperative therapies include laser recannulization and endoscopic dilation with or without stent placement. Patients who undergo stent placement for gastric outlet obstruction are frequently able to tolerate solid foods and may not require additional interventions. 65

66. Cutting edge: gastric carcinoma
H. pylori infection and gastric carcinoma
Cyclooxygenase-2 Activation and gastric carcinoma
Mini-invasive operation
Sentinel node
Neoadjunctive chemotherapy
Micrometastasis
Individualized treatment
Molecular Targeted Therapies

67. QUESTIONS
1. Definition of the advanced gastric cancer and its metastatic way
2. Krukenburg’s tumor

68. Thanks for your attention! the West Lake, Hangzhou, China