Gastric cancer

1、Gastric cancerThe department of Gastroenterology Shanghai Ren-Ji HospitalZhi Hua Ran (冉志华)Gastric Cancer Epidemiology Forth common types of cancerSecond most common cancer related death Geographic variations (ten times)Continuing decline Primarily a decline of distal GC (2000)(2000)Geographic variat

2、ions Geographic distribution of mortality rates for gastric cancer in males in ChinaGastric Cancer Environmental factorsH. pyloriGenetic factorsEtiological Factors of Gastric CancerPrecancerous changesThe role of H. Pylori infection in gastric carcinogensis Type I carcinogen1994 by IARCEpidemiologic

3、al studiesAnimal modes(Mongolian gerbil)Gastric CancerAttributable risk50%73%Honda et al . 1998Watanabe et al. 1998RF: 2.86 foldsEnvironmental factorsEnvironmental factors are involvedJapanese immigrants in US: 25%Second generation: 50%Subsequent generations: comparable to General US populationEnvir

4、onmental factorsLower socioeconomic statusTobacco/alcoholFresh vegetable/fruits/MicronutritionPoor food storageEating salted/Smoked foodMucosal damagePro-carcinogen/Carcinogen Lack of antioxidant GCGenetic factors The majority of gastric tumor are sporadic in nature There are rare inherited gastric

5、cancer predisposition traits such as germline p53 (Li-Fraumeni syndrome) E-cadherin (CDH1) alterations in diffuse gastric cancersPrecancerous changesPrecancerous lesionsPrecancerous conditionsPrecancerous lesions Defined as those pathological changes predisposed to gastric cancer dysplasia 10% of pa

6、tients 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 metaplasiaNature history of gastric dysplasiaNoDysplasiaMildDysplasiaModerateDysplas

7、iaHigh-gradeDysplasiaGastricadenocarcinoma5 years5 years5 years3 months-2 years10%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 ulcerGast

8、ric polypsPostulated sequence of histologic events in the progression to gastric adenocarcinoma and potential contributory factorsH. PyloriOther factorsChronic Superficial GastritisIntestinal MetaplasiaAtrophic GastritisDysplasiaFAP or AdenomasGastric AdenocarcinomaOther factorsAssociationStrong Ass

9、ociationCorrea hypothesis PathologyStagesMorphologyPathohistologic classificationMetastasisStages 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 submuc

10、osa 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 M1Morphology-early stage Morphology-early stage Morphology-early stage Morp

11、hology -advanced stagePathohistologic 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

12、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 inv

13、asionLymph node disseminationBlood spreadIntraperitoneal colonizationSpecial 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 th

14、e spread of stomach cancerClinical manifestationSigns 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 SymptomsAdvanced Gastric CancerW

15、eight 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-207UFT,5-DFURS-1, CAPE口服新药联合化疗FP: 5-FU+CDDP, b(bolus), CIV(continuous intravenous infu

16、sion)Latest advancement of 5-Fu applicationLV 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 effec

17、ts 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 dru

18、g 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% NoSemu

19、stine (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 Different mechanisms of action Compatible side effects Different mechanisms of resistanceSide effects of chemotherapyMucositisNausea/vomitingDiarrheaCystitisSterilityMyalgiaNeuropathyAlopeciaPulmonary fibrosisCardiotoxicityLocal reactionRenal failureMyelosuppressionPhlebitis Metal stentPrognosis The