Gastric cancer

Gastric cancer,The department of Gastroenterology Shanghai Ren-Ji HospitalZhi Hua Ran (冉志华),Gastric Cancer,Epidemiology,Forth common types of cancer,Second most common cancer related death,Geographic variations (ten times),Continuing decline,Primarily a decline of distal GC,(2000),(2000),Geographic variations,Geographic distribution of mortality rates for gastric cancer in males in China,Gastric Cancer,Environmental factors,H. pylori,Genetic factors,Etiological Factors of Gastric Cancer,Precancerous changes,The role of H. Pylori infection in gastric carcinogensis,Type I carcinogen1994 by IARC,Epidemiological studies,Animal modes(Mongolian gerbil),Gastric Cancer,Attributable risk50%73%,Honda et al . 1998Watanabe et al. 1998,RF: 2.86 folds,Environmental factors,Environmental factors are involved,Japanese immigrants in US: 25%,Second generation: 50%,Subsequent generations: comparable to General US population,Environmental factors,Lower socioeconomic status,Tobacco/alcohol,Fresh vegetable/fruits/Micronutrition,Poor food storage,Eating salted/Smoked food,Mucosal damage,Pro-carcinogen/Carcinogen,Lack of antioxidant,GC,Genetic factors,The majority of gastric tumor are sporadic in nature There are rare inherited gastric cancer predisposition traits such as germline p53 (Li-Fraumeni syndrome) E-cadherin (CDH1) alterations in diffuse gastric cancers,Precancerous changes,Precancerous lesions,Precancerous conditions,Precancerous lesions,Defined as those pathological changes predisposed to gastric cancer dysplasia 10% of patients may progress in severity majority of patients either regress or remain stable High-grade dysplasia may be only a transient phase in the progression to gastric cancer occurs in atrophic gastritis or intestinal metaplasia,Nature history of gastric dysplasia,NoDysplasia,MildDysplasia,ModerateDysplasia,High-gradeDysplasia,Gastricadenocarcinoma,5 years,5 years,5 years,3 months-2 years,10%,10%,50%-90%,60%,60%,10%,Precancerous condition,Defined as those clinical setting with higher risk of developing gastric cancerChronic atrophic gastritisGastrectomyPernicious anemiaMenetriers diseaseChronic gastric ulcerGastric polyps,Postulated sequence of histologic events in the progression to gastric adenocarcinoma and potential contributory factors,H. Pylori,Other factors,Chronic Superficial Gastritis,Intestinal Metaplasia,Atrophic Gastritis,Dysplasia,FAP or Adenomas,Gastric Adenocarcinoma,Other factors,Association,Strong Association,Correa hypothesis,Pathology,Stages,Morphology,Pathohistologic classification,Metastasis,Stages,Early stage limited in the mucosa and submucosa layers, no matter with or without lymph node metastasis Classified by the Japanese Society for Gastric Cancer 1cm 0.5cm Advanced stage invaded over submucosa According to Bormann classification,TNM classification (UICC),0 Tis N0 M0 III A T2 N2 M0 I A T1 N0 M0 T3 N1 M0 I B T1 N1 M0 T4 N0 M0 T2 N0 M0 III B T3 N2 M0 II T1 N2 M0 IV T4 N2 M0 T2 N1 M0 T13 N3 M0 T3 N0 M0 any T any N M1,Morphology-early stage,Morphology-early stage,Morphology-early stage,Morphology -advanced stage,Pathohistologic classification,HistologyAdenocarcinoma 90%Lymphoma 5%Stromal 2%Carcinoid 1%Metastasis 1%Adenosquamous/squamous 1%Miscellaneous 1%,Origin (Lauren),Intestinal type associated with most environmental risk factors carries a better prognosis shows no familial history Diffuse type consists of scattered cell clusters with poor prognosis,Growth pattern (Ming),Expanding type grew en mass and by expansion resulting in the formation of discrete tumor nodules with relatively good prognosis Infiltrative type invaded individually with poor prognosis,Metastasis,Direct invasion,Lymph node dissemination,Blood spread,Intraperitoneal colonization,Special term,Blumer shelf A shelf palpable by reactal examination, due to metastatic tumor cells gravitating from an abdominal cancer and growing in the rectovesical or rectouterine pouch Krukenberg tumor A tumor in the ovary by the spread of stomach cancer,Clinical manifestation,Signs and SymptomsEarly Gastric CancerAsymptomatic or silent 80%Peptic ulcer symptoms 10%Nausea or vomiting 8%Anorexia 8%Early satiety 5%Abdominal pain 2%Gastrointestinal blood loss 2%Weight loss 2%Dysphagia 1%,Signs and Symptoms,Advanced Gastric CancerWeight loss 60%Abdominal pain 50%Nausea or vomiting 30%Anorexia 30%Dysphagia 25%Gastrointestinal blood loss 20%Early satiety 20%Peptic ulcer symptoms 20%Abdominal mass or fullness 5%Asymptomatic or silent 50%,衍化新药,FT-207,UFT,5-DFUR,S-1, CAPE,口服新药联合化疗,FP: 5-FU+CDDP, b(bolus), CIV(continuous intravenous infusion),Latest advancement of 5-Fu application,LV bio-regulation: exogenous LV may enhance the inhibitory effect of 5-Fu TSAdministration of LV/5-Fu: LV first, followed by 5-FuStandard (Mayo Clinic) LV 20mg/m2 b. 5-Fu 425 mg/m2 b.LV 200mg/m2 I.V. 2h, 5-Fu 370 mg/m2 b.CIV: CIV enhance the cytotoxic effects of 5-FU 6001500mg/m2 CIV 24h x 2d,q2w 300800mg/m2 CIV 24h x 5d, q3wCapecitabine (Xeloda),5-Fu+Pts combination regime,5-Fu + CDDP (HD,LD) both are effective HD CDDP - cytotoxic effect LD CDDP - bio-regulation effect HD vs LD CDDP to treat AGC: same RR% LD CDDP + 5-Fu: conductive to adding third drug The recommondated dose: HD CDDP 50100mg/m2 I.V. 4h,q3w LD CDDP 1520mg/m2 I.V. 2h, x5d q3wOxaliplatin is more commomly employed in combination regime,Chemotherapy,Regimen Approximate Survival Response rate BenefitFluorouracil +doxorubicin 30% No+ mitomycin (FAM)Fluorouracil + doxorubicin 30% NoSemustine (FAMe) Fluorouracil + doxorubicin 30% No+ cisplatin (FAP)Etoposide + doxorubicin 40% No+ cisplatin (EAP)Etoposide + leucovorin 30% No+ fluorouracil (ELF)Fluorouracil +doxorubicin 40% Unconfirmed+ methotrexate (FAMTX),AIM OF COMBINATION THERAPY,INCREASED EFFICACY,Different mechanisms of action Compatible side effects Different mechanisms of resistance,ACTIVITY,SAFETY,Side effects of chemotherapy,MucositisNausea/vomitingDiarrheaCystitisSterilityMyalgiaNeuropathy,AlopeciaPulmonary fibrosisCardiotoxicityLocal reactionRenal failureMyelosuppressionPhlebitis,Metal stent,Pro