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Gastric Cancer Zhejiang University Ji-Ren Yu Department of GI Surgery The First Affiliated Hospital College of Medicine, Zhejiang University Slide 2 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; iii) lower rates in Western Europe and the United States. Zhejiang University Slide 3 Correa P Cancer Epidemiol Biomarkers Prev 2003;12:238s-241s Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006;12(3):354-362 Epidemiology Incidence per 100,000 Slide 4 Gastric Cancer 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 Zhejiang University Slide 5 iii) Social Low social class iv) Medical Prior gastric surgery Helicobacter pylori infection Gastric atrophy and gastritis Adenomatous polyps Pernicious anemia Gastric Cancer Risk Factors Zhejiang University Slide 6 Etiological Factors (Risk Factors) Slide 7 A Model for the Pathogenesis of the Gastric Cancer Slide 8 i) Early gastric cancer(EGC) Gastric cancer confined to the mucosa or submucosa, regardless of the presence or absence of lymph node metastasis Pathology ii) Advanced gastric cancer(AGC) Cancer cells infiltrate the proprial muscle layer or serosa Zhejiang University Slide 9 EGC Pathology I: protruded IIa: superficially elevated IIc: superficially depressed IIb: superficially flat III: excavated Slide 10 EGC:Endoscopic images Type I Type IIType III Slide 11 Pathology Borrmann's pathologic classification of gastric cancer based on gross appearance AGC: Borrmanns classification Linitis plastica Slide 12 T stage are defined by depth of penetration into the gastric wall T stage Lamina propria T 1a T 1b T 4a T 4b T3T3 Subserosal connective tissue T 1b T 1a T 4a T 4b Slide 13 Slide 14 Slide 15 Staging Grouping of Regional Lymph Nodes (Groups 1-3) by Location of Primary Tumor According to the Japanese Classification of Gastric Carcinoma N stage Slide 16 LOCATION OF PRIMARY TUMOR IN STOMACH LYMPH NODE STATION (NO.)DESCRIPTIONUpper ThirdMiddle ThirdLower Third 1Right paracardial112 2Left paracardial13M 3Lesser curvature111 4saShort gastric13M 4sbLeft gastroepiploic113 4dRight gastroepiploic211 5Suprapyloric311 6Infrapyloric311 7Left gastric artery222 8aAnterior comm. hepatic222 8pPosterior comm. hepatic333 9Celiac artery222 10Splenic hilum23M 11pProximal splenic222 11dDistal splenic23M 12aLeft hepatoduodenal322 12b,pPosterior hepatoduodenal333 13RetropancreaticM33 14vSuperior mesenteric veinM32 14aSuperior mesenteric arteryMMM 15Middle colicMMM 16alAortic hiatus3MM 16a2,b1Para-aortic, middleM33 16b2Para-aortic, caudalMMM M, lymph nodes regarded as distant metastasis Slide 17 Metastesis Direct invasion Lyphmatic metastesis Hematogenous metastasis Seeding metastasis Slide 18 Clinical Presentation i)Lacks specific symptoms early: vague epigastric discomfort indigestion. ii)Epigastric pain is constant, nonradiating, and unrelieved by food ingestion. iii)Advanced disease may present with weight loss, anorexia, fatigue, or vomiting. iv)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. v) Hematemesis, anemic. vi)Very large tumors erode into the transverse colon, presenting as large bowel obstruction. Slide 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. Slide 20 Endoscopy M SCT (multiple detector-row spiral CT) BUS & EUS double-contrast radiography MRI DL (diagnostic laparoscopy ) PET-CT Examination Slide 21 Clinicpathological Staging EUS Laprascopy BUS CT PET- CT CT is the mainly procedure MRI Slide 22 Endoscopy Carcinoma in situ Advanced carcinoma Slide 23 Niche Double-Contrast Barium Upper GI Radiography Slide 24 EUS Slide 25 T T N Slide 26 CT scan Borrmann I Slide 27 T NH1H1 T4N2M1 CT Scan Slide 28 PET-CT: T3N2 Slide 29 BUS Liver metastasis Krukenbergs tumor left right Slide 30 T T Laparoscopy Abdominal metastasis Slide 31 Treatment for Gastric Cancer Surgery Endoscopic mucosal resection (EMR) Endoscopic submucosal dissection (ESD) Laparoscopic Surgery Open Surgery Chemotherapy Chemoradiotherapy Target therapy et,al Slide 32 EMR for Earlier gastric cancer (EGC ) Slide 33 Criteria for EMR NCCN 2011 V1. 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, 5458) 1.differentiated adenocarcinoma; 2.Intramucosal cancer; 3.20 mm in size; 4.without ulcer finding Slide 34 EMR Slide 35 Slide 36 Slide 37 1. Difficult to resect large than 20mm tumor in size 2. Difficult to resect ulcerative lesions Limitation of EMR techniques ESD has been developed Slide 38 ESD for EGC Slide 39 ESD Oita Digestive Organs Hospital Slide 40 ESD Oita Digestive Organs Hospital Slide 41 Criteria for ESD National Cancer Center Hospital In Japan ( evaluation for histological curability ) ( indication for DST ) Slide 42 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 Surgical Treatment for Gastric Cancer Slide 43 Laparoscopic Resection i) A suitable procedure for ECG ( Our experience ) ii) The efficacy and safety of this approach for advanc gastric carcinoma requires further investigation to be evaluated Slide 44 Open Surgery for Advanced Gastric Cancer i) A suitable procedure for ACG ii) R0 resection iii) R1 resection iv) R2 resection Slide 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 Slide 46 Gastrectomy and D2 lymphadenectomy for advanced gastric carcinoma Gastrectomy Slide 47 Slide 48 Slide 49 Slide 50 Left gastric A Hepatic A Splenic A No.11 LN Slide 51 PORTAL VEIN Slide 52 Slide 53 Slide 54 Slide 55 Ligaments of liver and stomach disection Right gastric arteries disection Right gastroepiploic arteries disection Ligaments of spleen-stomach disection N7,N8,N9 disection esophagus disection N12 N13 disection Viedo of operation Slide 56 Adjuvant Therapy Radiation Therapy Chemotherapy Targeted Therapy Slide 57 ECF: Epirubicin, Cisplatin, SOX: S-1, Oxaliplatin XELOX: Capecitabin, Oxaliplatin DCF: Docetaxel, Cisplatin, 5-Fu Chemotherapy Regimens Preoperative Chemotherapy Postoperative Chemotherapy Slide 58 Ulcerative mass at antrum of stomach about 4*5cm in size The lesion is about 2.0*1.0cm in size After 3 courses FOLFOX6 Before the neoadjvant chemotherapy Our experience Preoperative chemotherapy Slide 59 Before the neoadjvant chemotherapy After 3 courses of XELOX Our experience Slide 60 Lymphadectomy of group 7,8,9 Slide 61 Our experience Liver after Chemotherapy Slide 62 foam cells in lamina propria(4010) Our experience Slide 63 Targeted Therapy Herccptin Herb-2 receptor inhibitor Iressa EGFR inhibitor Avastin VEGFR inhibitor Slide 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 Slide 65 Palliative Treatment Surgical palliation resection or bypass alone or in conjunction with percutaneous, endoscopic, or radiotherapy techniques laser recannulization and endoscopic dilation with or without stent placement Nonoperative therapies Slide 66 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 Cutting edge: gastric carcinoma Slide 67 1. Definition of the advanced gastric cancer and its metastatic way 2. Krukenburgs tumor QUESTIONS Slide 68 the West Lake, Hangzhou, China