1. 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
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. Epidemiology
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69. 2

3. Epidemiology
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69.

4. Risk Factors 1. Nutrition 2. Environment and Heredity
Low fat or protein consumption
Salted meat or fish
High nitrate consumption
High complex-carbohydrate consumption
2. Environment and Heredity
Poor food preparation (smoked, salted)
Lack of refrigeration
Poor drinking water (well water)
Smoking 4

5. Risk Factors 3.Social 4.Medical
Low socioeconomic status (except in Japan)
4.Medical
Prior gastric surgery Helicobacter pylori infection
Gastric atrophy and gastritis Adenomatous polyps
Pernicious anemia
Male gender
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. Correa mode of the pathogenesis of human gastric adenocarcinoma
Pathology
Correa mode of the pathogenesis of human gastric adenocarcinoma
A model of the pathogenesis of human gastric adenocarcinoma shows that Human gastric carcinogenesis is a multistep and multifactoral process 7

8. Pathology 1.Early gastric cancer (EGC)
Gastric cancer confined to the mucosa or submucosa, regardless of the presence or absence of lymph node metastasis
2. Advanced gastric cancer (AGC)
Cancer cells infiltrate the proprial muscle layer or serosa

9. EGC Pathology IIb: superficially flat I: protruded
IIc: superficially depressed
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.
IIa: superficially elevated
III: excavated 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 classification of gastric cancer based on gross appearance 11

12. T stage
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

13. 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 13

14. 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. 14

17. Clinical Presentation
1. Lacks specific symptoms early: vague epigastric discomfort indigestion.
2. Epigastric pain is constant, nonradiating, and unrelieved by food ingestion.
3. Advanced disease may present with weight loss, anorexia, fatigue, or vomiting.
4. 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.
5. Hematemesis, anemic.
6. 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. 17

18. Physical signs 1. A palpable abdominal mass,
2. A palpable supraclavicular or periumbilical \lymph node,
3. Peritoneal metastasis palpable by rectal examination
4. A palpable ovarian mass (Krukenberg's tumor).
5. 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. 18

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

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

21. Endoscopy Advanced carcinoma Carcinoma in situ
When gastric cancer is suspected based on history and physical examination, flexible upper endoscopy is the diagnostic modality of choice
Advanced carcinoma
Carcinoma in situ 21

22. Double-Contrast Barium Upper GI Radiography
Niche
A Niche can be shown by double-contrast barium upper GI radiography in ulcerating tumor. 22

23. EUS EUS can detect the tumor infilltrated layer of the gastric wall.23

24. EUS T N
EUS aslo can detect the enlarged perigastric lymph nodes. 24

25. CT scan

26. CT scan A B C T N H1
T4N2M1

27. PET-CT: T3N2

28. 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 28

29. Laparoscopy T T Abdominal metastasis
Diagnostic laparoscopy detected metastases on the peritoneum and round ligaments of liver T
Abdominal metastasis 29

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

31. 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. 31

32. Criteria for EMR NCCN 2011 V2. Japanese Gastric Cancer Association
1.Early gastric cancer (Tis or T1a tumors limited)
2. Well-differentiated or moderately differentiated histology
3.Tumors less than 15mm in size,
4.Absence of ulceration and no evidence of invasive finding
Japanese Gastric Cancer Association
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. 32

33. EMR

34. EMR

35. EMR

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

37. ESD 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. 37

38. ESD
Oita Digestive Organs Hospital

39. ESD
Oita Digestive Organs Hospital

40. Criteria for ESD
National Cancer Center Hospital In Japan

41. Surgical Treatment for Gastric Cancer
Principles of radical operation for gastric cancer
1. Negative margin (R0 resection, adequate margins ≥4 cm )
2. D2 lymph node dissection for advance gastric cancer
3. Subtotal gastrectomy for distal gastric cancer
4.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. 41

42. Laparoscopic Resection
1. A suitable procedure for ECG (Our experience) 2. The efficacy and safety of this approach for advanc gastric carcinoma requires further investigation
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. 42

43. Open Surgery for Advanced Gastric Cancer
1. A suitable procedure for ACG
2. R0 resection
3. R1 resection
4. R2 resection

44. 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 gastric cancer in eastern Asia

45. Gastrectomy and D2 lymphadenectomy for advanced gastric carcinoma
For advance gastric carcinoma, open surgical resection are recommended. 45

46. Lymphadenectomy
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. 46

47. Anastomosis Subtotal gastrectomy Billroth II anastomosis
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.
Billroth II anastomosis
Roux-en-Y anastomosis
Subtotal gastrectomy 47

48. Total gastrectomy
Body and midstomach tumors typically require a total resection to gain adequate margins of at least 6 cm. 48

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

50. Portal Vein

51. Stomach Spleen Greater omentum
Tumor located at the midstomach which has invased into the spleen. Total gastrectomy in combination with splenoectomy was done.
Greater omentum 51

54. 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. 54

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

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

57. Preoperative chemotherapy
After 3 courses of XELOX

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

59. Liver after Chemotherapy
Our experience

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

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

62. 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

63. Palliative Treatment Surgical palliation
Resection or bypass alone or in conjunction with percutaneous, endoscopic, or radiotherapy techniques
Nonoperative therapies
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.
Laser recannulization and endoscopic dilation with or without stent placement 63

64. 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

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

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