Gastric Cancer: Status & Outlook at First Affiliated Hospital, Zhejiang University

1. 胃癌治疗的现状和展望 浙江大学附属第一医院 胃肠外科 于吉人 Ji-Ren Yu Department of GI Surgery, The First Affiliated Hospital, Zhejiang University

2. Epidemiology • The fifthmost common cancer worldwide • The third most common cause of death from cancer • Higher rates in Eastern Asia, South America, Eastern Europe • Lower rates in Western Europe and the United States GLOBOCAN 2012

3. Epidemiology Global: 952 thousands newly diagnosed GC per year Asian: 73.5% China: 42.5%

4. Nutritional Low fat or protein consumption Salted meat or fish High nitrate consumption High complex carbohydrate consumption Causes

5. Environmental Poor food preparation (smoked, salted) Lack of refrigeration Poor drinking water Smoking Causes

6. Medical Prior gastric surgery H. pylori infection （幽门螺杆菌感染）） Gastric atrophy and gastritis Adenomatous polyps Others Male gender Low social class Causes

7. Hereditary Hereditary Diffuse Gastric Cancer 遗传性弥漫性胃癌 Lynch Syndrome Lynch 综合征 Juvenile Polyposis Syndrome 幼年性息肉病综合征 Peutz-Jeghers Syndrome 黑斑息肉综合征 Familial Adenomatous Polyposis 家族性腺瘤样息肉病 Causes NCCN 2017 ver. 1

8. NCCN 2017 ver. 1

9. i) Early gastric cancer(EGC) Pathology 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

10. Macroscopic type EGC I: protruded 隆起型 IIa: superficially elevated 浅表隆起型 IIb: superficially flat 浅表平坦型 IIc: superficially depressed 浅表凹陷型 III: excavated 凹陷型 Japanese Endoscopy Society Classification

11. EGC:Endoscopic images Type I Type II Type III

12. Macroscopic type AGC:Borrmann’s classification Type I: Mass 巨块型 Type II: Ulcerative 局限溃疡型 Type III: Infiltrative ulcerative 浸润溃疡型 Type IV: Diffuse infiltrative 弥漫浸润型 Linitis plastica

13. Macroscopic type AGC:Borrmann’s classification Type I: Mass

14. Macroscopic type AGC:Borrmann’s classification Type II: Ulcerative

15. Macroscopic type AGC:Borrmann’s classification Type III: Infiltrative ulcerative

16. Macroscopic type AGC:Borrmann’s classification Type IV: Diffuse infiltrative

17. T stage

18. Lymph node station

19. Lymph node station

20. Metastesis Direct invasion Lyphmatic metastesis Hematogenous metastasis Seeding metastasis

23. AJCC TNM staging classification update 8th edition 2018 A Tumor center is located below the gastroesophageal junction, > 2 cm, and the tumor invade the gastroesophageal junction Gastric Cancer Classification B Tumor center is located below the gastroesophageal junction, < 2 cm, but the tumor doesn’t invade the gastroesophageal junction Gastric Cancer Classification C Tumor center is located below the gastroesophageal junction, < 2 cm, and the tumor invade the gastroesophageal junction Esophageal cancer Classification

24. AJCC TNM staging classification update 8th edition 2018 Clinical TNM classification (cTNM)

25. AJCC TNM staging classification update 8th edition 2018 7 th ed. 8 th ed.

26. AJCC TNM staging classification update 8th edition 2018 Post-chemotherapy classification (yTNM)

27. Clinical Presentation Lacks specific symptoms early: vague, epigastric discomfort, indigestion. Epigastric pain, nonradiating and unrelieved by food ingestion. Weight loss, anorexia, fatigue or vomiting. Hematemesis, anemic. Large bowel obstruction.

28. Physical signs i) A palpable abdominal mass ii) A palpable supraclavicular or periumbilical lymph node ii) Peritoneal metastasis palpable by rectal examination iii) A palpable ovarian mass (Krukenberg's tumor). iv) Jaundice, ascites, and cachexia.

29. CT Investigations Laparoscopy Endoscopy EUS/BUS MRI PET-CT CT is the mainly procedure

30. Endoscopy

31. Double-Contrast Barium Upper GI Radiography Antrum Cardia Linitis plastica

32. EUS

33. EUS T N T

34. BUS left right right Liver metastasis Krukenberg’s tumor

35. CT scan

36. A B C N M T CT scan T4N2M1

37. MRI-DWI

38. PET/CT

39. Laparoscopy T T Abdominal metastasis

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

41. NCCN Guideline ADDITIONAL EVALUATION CLINICAL STAGE FINAL STAGE PRIMARY TREATMENT Non-surgical candidate Tis or T1a ER Tis / T1a ER orSurgery Tis or T1a Medically fit Surgery T1b Potentially resectable Potentially resectable Surgery or Pre-operative treatment T2 or higher, Any N Consider laparoscopy M0 Unresectable M0 Unresectable Chemoradiation or Chemotherapy Non-surgical candidate Non-surgical candidate Chemoradiation or Palliative Management M1 Palliative Management Stage IV (M1)

42. JGCA Guideline

43. Resectable Tumors Tis or T1a------EMR/ESD T1b-T3-----Gastrectomy with negative microscopic margins (typically ≥4 cm from gross tumor) T4-----En bloc resection of involved structures NCCN2017 Ver. 1 Gastrectomy plus D1/D2

44. Unresectable Tumors Locoregionally advanced Local advanced disease (N3 or N4 lymph node involvement highly suspicious on imaging or confirmed by biopsy Invasion or encasement of major vascular structures (excluding the splenic vessels) Distant metastasis or peritoneal involvement (including positive peritoneal cytology) NCCN 2017 Ver. 1 Palliative Treatment

45. EMR for Earlier gastric cancer (EGC )

46. Criteria for EMR/ESD • NCCN 2017. Ver.1: • 1.Tis or T1a • 2. Well or moderately differentiated histology • 3.Tumors less than 20mm in size • 4. Clear lateral and deep margins • 5. Without evidence of ulceration，lymph node metastasis or lymphovascular invasion (LVI）

47. Criteria for EMR/ESD Japanese Gastric Cancer Association • Absolute indication (EMR/ESD): • Differentiated adenocarcinoma • cT1a • diameter is ≤2 cm • without ulcer finding (UL-) • Absolute indication (ESD): • Tumors clinically diagnosed as T1a and: • (a) Differentiated, UL( - ), but>2 cm • (b) Differentiated-type, UL(+), and ≤ 3 cm • (New Added 2017.ver.5 ) A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer (cT1a): the Japan Clinical Oncology Group study(JCOG0607). Gastric Cancer. 2017 Feb 21.

48. Criteria for EMR/ESD Japanese Gastric Cancer Association • Expanded indication (ESD): • Tumors clinically diagnosed as T1a and: • (a) Undifferentiated-type, UL(-), and ≤ 2cm • (New Added 2017.ver.5 ) A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer (cT1a): the Japan Clinical Oncology Group study(JCOG0607). Gastric Cancer. 2017 Feb 21.

49. EMR

50. EMR