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CARCINOMA STOMACH EPIDEMIOLOGY 90- 95% OF MALIGNANT TUMOURS OF STOMACH WORLDWIDE DISEASE - 3% OF CANCER DEATHS JAPAN,COLOMBIA,COSTA RICA, HUNGARY - HIGH INCIDENCE LOW INCIDENCE –USA,UK,CANADA EPIDEMIOLOGY RACIAL FACTORSHIGHER INCIDENCE IN BLACKS, AMERICAN INDIANS, NORTH WALES,CHINESE IN INDONANESIA GENETIC FACTORS – 4% OF PATIENTS HAVE FAMILY HISTORY INDIVIDUALS WITH BLOOD GROUP A HAVE HIGHER INCIDENCE CARCINOMA STOMACH PATHOGENESIS TWO MORPHOLOGIC TYPES 1.INTESTINAL TYPE – ARISE FROM INTESTINAL METAPLASIA, MORE COMMON TYPE-ABOVE 50YRS M:F- 2:1 2. DIFFUSE TYPE- ARISE De NOVO FROM GASTRIC MUCOUS CELLS. OVER 60 YRS M:F-EQUAL RISK FACTORS FOR GASTRIC CARCINOMA INTESTINAL TYPE 1. DIET A.NITRITES FROM FOOD, DRINKING WATER,AS PRESERVATIVES IN PREPARED MEALS- UNDERGO NITROSATION TO FORM NITROSAMINES & NITROSAMIDES B. SMOKED FOOD & PICKLED VEGETABLES C. EXCESSIVE SALT INTAKE PATHOGENESIS OF INTESTINAL TYPE D. DECREASED INTAKE OF FRESH VEGETABLES & FRUITS ANTIOXIDANTS PRESENT IN THESE FOODS INHIBIT NITROSATION 2. CHRONIC ATROPHIC GASTRITIS WITH INTESTINAL METAPLASIA A. INFECTION WITH HELICOBACTOR PYLORI- MAJOR RISK FACTOR- HOW ? PATHOGENESIS THESE PATIENTS DEVELOP SEVERE GASTRIC ATROPHY,INTESTINAL METAPLASIA ULTIMATELY DYSPLASIA & CANCER- CHRONIC INFLAMMATION- DNA DAMAGING FREE RADICALS- MUTATIONSHYPERPROLIFERATION NOT BALANCED BY APOPTOSIS B.PERNICIOUS ANEMIA PATHOGENESIS 3.ALTERED ANATOMY AFTER SUBTOTAL DISTAL GASTRECTOMY- STUMP CARCINOMA 4. MENETRIER’S DISEASE – GASTRIC PIT HYPERPLASIA & CYST FORMATION PATHOGENESIS 5. ADENOMAS- SIZE 2cms OR MORE PATHOGENESIS A STEP IN MALIGNANT PROGRESSION IS APPEARANCE OF GASTRIC EPITHELIAL DYSPLASIA(GED)-LOW OR HIGH GRADE. LOW GRADE IS REVERSIBLE IN 66% CASES LOCATION OF GASTRIC CARCINOMA WITHIN THE STOMACH PYLORUS & ANTRUM- 50- 60% CARDIA – 25% REMAINDER IN THE BODY & FUNDUS LESSOR CURVATURE- 40% GREATER CURVATURE – 12% FAVOURED LOCATION IS THE LESSOR CURVATURE OF THE ANTROPYLORIC REGION. CLASSIFICATION ON THE BASIS OF DEPTH OF INVATION & & MACROSCOPIC GROWTH PATTERN & HISTOLOGIC SUBTYPE.THE MORPHOLOGIC FEATURE HAVING THE GREATEST IMPACT ON CLINICAL OUTCOME IS THE DEPTH OF INVASION EARLY GASTRIC CARCINOMA LESION CONFINED TO THE MUCOSA & SUBMUCOSA,REGARDLESS OF THE PRESENCE OR ABSENCE OF PERIGASTRIC LYMPH NODE METASTASIS ADVANCED GASTRIC CARCINOMA ADVANCED GASTRIC CARCINOMA IS A NEOPLASM THAT HAS EXTENDED BELOW THE SUBMUCOSA INTO THE MUSCULAR WALL. INTESTINAL TYPE- ADVANCED GASTRIC CARCINOMA-GROSS • INTESTINAL TYPE OF ADENOCARCINOMA CLOSELY RESEMBLE COLONIC CANCERS – TEND TO BE 1. POLYPOID 2. FUNGATING – PROTRUDING LARGER WITH EXTENSIVE ULCERATION OF THE TOP INTESTINAL TYPE- ADVANCED GASTRIC CARCINOMA-GROSS 3. ULCERATED OR EXCAVATED TYPE 4.COLLOID TYPE 5.DEPRESSED OR FLAT TYPE & ARE WELL DEMARCATED 6.ULCER CANCER- ? MACROSCOPIC GROWTH PATTERNS EXOPHYTIC TUMOUR( POLYPOID OR FUNGATING) MAY CONTAIN PORTIONS OF ADENOMA DEPRESSED OR FLAT TYPE- LOOK LIKE EFFACEMENT OF NORMAL MUCOSAL PATTERN CARCINOMA STOMACH ULCERATIVE TYPE LARGE EXCAVATING ULCER WITH HEAPED UP MARGINS & NECROTIC BASE. MACROSCOPIC GROWTH PATTERNS EXCAVATED CANCER MAY MIMIC IN SIZE & APPEARANCE CHRONIC PEPTIC ULCERS.MORE ADVANCED CASES EXHIBIT HEAPED UP MARGINS MACROSCOPIC GROWTH PATTERNS 7. DIFFUSELY INFILTRATING TYPE. A LARGE REGION OF GASTRIC WALL OR THE ENTIRE STOMACH MAY BE EXTENSIVELY INFILTRATED BY MALIGNANCY. MACROSCOPIC GROWTH PATTERN THIS REGID & THICKENED STOMACH IS TERMED LEATHER BOTTLE STOMACH OR LINITIS PLASTICA – SEEN IN DIFFUSE TYPE OF CARCINOMA. METASTASIS FROM BREAST & LUNG MAY GENERATE A SIMILAR PICTURE MACROSCOPIC GROWTH PATTERN ULCERATED CARCINOMAS MAY BE DISTINGUISHED FROM CHRONIC GASTRIC PEPTIC ULCER BY BEING GROSS • BIGGER,MORE IRREGULAR & HAVING HEAPED UP OR ROLLED EDGE. • ANY ENDOSCOPICALLY SUGGESTIVE LESION IN THE STOMACH SHOULD HAVE MULTIPLE BIOPSIES TAKEN FOR PATHOLOGIC EVALUATION,TAKEN FROM AN EDGE RATHER THAN BASE. GROSS FEATURES OF BENIGN & MALIGNANT GASTRIC ULCERS • BENIGN MALIGNANT • SIZE SMALLER LARGER • SHAPE REGULAR IRREGULAR • BORDERS OEDEMATOUS HEAPED UP • MUCOSAL FOLDS RADIATING • ULCER BED CLEAN INTERRUPTED NECROTIC HISTOLOGIC(MICROSCOPIC) CLASSIFICATION 1.WHO CLASSIFICATION – PAPILLARY, TUBULAR , MUCINOUS & SIGNET RING TYPES – EASY TO APPLY & REPRODUCIBLE BUT HAS NO VALUE IN STUDIES OF PATHOGENESIS OR ETIOLOGY. HISTOLOGIC(MICROSCOPIC) CLASSIFICATION 2.SYSTEM OF LAUREN2 TYPES INTESTINAL & DIFFUSE – MORE USEFUL- CORRELATED WELL WITH ETIOPATHOGENESIS MICROSCOPIC PICTURE INTESTINAL TYPE 1. WELL FORMED GLANDULAR PATTERN 2. MAY HAVE SOLID OR PAPILLARY AREAS- INDIVIDUAL CELLS ARE COLUMNAR OR CUBOIDAL WITH A BASALLY LOCATED NUCLEI. MICROSCOPICAL PICTUREINTESTINAL TYPE 3. CELLS WITH INTRACYTOPLASMIC MUCIN ARE UNCOMMON, ALTHOUGH MUCIN MAY BE SEEN WITH IN THE GLAND LUMENS INTESTINAL TYPE CARCINOMA BRUSH CYTOLOGY OF GASTRIC CARCINOMA- INTESTINAL TYPE MICROSCOPICAL PICTUREINTESTINAL TYPE INTESTINAL TYPE OF CARCINOMA CAN BE WELL TO MODERATELY TO POORLY DIFFERENTIATED. MORPHOLOGY- DIFFUSE TYPE GROSS- MORE LIKELY TO HAVE A PLAQUE LIKE SURFACE COMPONENT & AN ILL-DEFINED WIDELY INFILTRATING GROWTHLEATHER BOTTLE STOMACH (LINITIS PLASTICA). MORPHOLOGY- DIFFUSE TYPE MICROSCOPY - COMPOSED OF INDIVIDUAL & SMALL GROUPS OR CORDS OF CELLS. STROMA IS FIBROUS OR MUCOID. MANY TUMOUR CELLS CONTAIN MUCIN DROPLETS GIVING A SIGNET RING CONFIGURATION. SIGNET RING CELL CARCINOMA MICROSCOPY 16 % OF CARCINOMA STOMACH ARE UNCLASSIFIED OR OF MIXED TYPE. PROGNOSTIC FACTORS OVERALL PROGNOSIS OF GASTRIC CARCINOMA IS POOR. WITH AN AVERAGE 5 YEAR SURVIVAL OF ONLY 10 – 15 %. PROGNOSTIC FACTORS ADVERSE PROGNOSTIC FACTORS ARE 1. AGE OLDER THAN 70 YRS. PROGNOSTIC FACTORS 2. CEA ANTIGEN MORE THAN 10ng /ml 3. CA19 -9 MORE THAN 37 MICROGRAM/ml PROGNOSTIC FACTORS 4. SURVIVAL IS HIGH WITH INTESTINAL TYPE BECAUSE THEY ARE GENERALLY PRESENT EARLIER WITH LESS ADVANCED DISEASE. WHEN MATCHED STAGE FOR STAGE NO DIFFERECE IN SURVIVAL BETWEEN THE TWO TUMOUR TYPES 5. STAGE OF THE TUMOUR SPREAD THREE MODES OF SPREAD 1. LYMPHATIC –LYMPH NODE 2. BLOOD STREAM 3. TRANSPERITONEAL ROUTE LYMPHATIC SPREAD LYMPH NODES ALONG GREATER & LESSER CURVATURE 70% OF RESECTED SPECIMENS EARLY SPREAD VIA THORACIC DUCT LATER SPREAD TO PORTA HEPATIS, PARAAORTIC NODES LYMPHATIC SPREAD SOMETIMES THORACIC DUCT TO LEFT SUPRACLAVICULAR NODES VIRCHOW NODES. SPREAD LATER LUNGS, BRAIN, BONES,KIDNEYS ,ADRENALS & OTHER DISTASNT SITES ARE INVOLVED BY HAEMATOGENOUS ROUTE TRANSRPERITONEAL SPREAD – INTRAABDOMINAL SITESPARTICULARLY PELVIS , OVARIES. SPREAD • KRUKENBERG’S TUMOUR IS BILATERAL OVARIAN METASTASES OF A SIGNET RING CARCINOMA. DIAGNOSIS • STAINING WITH ALCIAN BLUE WITH PAS STAIN HELPS IN DIAGNOSIS ON A BIOPSY • BRUSH CYTOLOGY OF THESE LESIONS-85 % ACCURATE. EARLY GASTRIC CARCINOMA PRIMARY GROWTH IS CONFINED TO THE MUCOSA OR SUBMUCOSA OF THE STOMACH, MAY BE ASSOCIATED WITH LOCAL LYMPH NODE METASTASES OR EVEN HEPATIC METASTASES. MOST ARE CURABLE BY SURGERY. MORPHOLOGY EARLY GASTRIC CARCINOMA SUBCLASSIFIED INTO • FLAT • ELEVATED • PROTRUDED • DEPRESSED • EXCAVATED • COMBINED FORMS EARLY GASTRIC CARCINOMA MORPHOLOGY • HISTOLOGY OF EARLY GASTRIC CARCINOMA IS SIMILAR TO THAT OF ADVANCED CANCER WITH INTESTINAL, DIFFUSE OR MIXED FORMS. TNM STAGING OF GASTRIC CARCINOMA. Tis- CARCINOMA IN SITU T1 – INVASION OF LAMINA PROPRIA OR SUBMUCOSA T2- INVASION OF MUSCULARIS PROPRIA OR SUBSEROSA TNM STAGING OF GASTRIC CARCINOMA. T3- TUMOUR PENETRATES VISCERAL PERITONIUM T4 – TUMOUR INVADES ADJACENT STRUCTURES TNM STAGING CONTINEUD N0 -- NO REGIONAL NODES INVOLVED NI – 1-6 REGIONAL NODES INVOLVEMENT TNM STAGING CONTINEUD N2 – 7- 15 REGIONAL NODES INVOLVEMENT N3 – MORE THAN 15 REGIONAL NODE INVOLVEMENT TNM STAGING OF GASTRIC CARCINOMA- CONTI • M0 - NO DISTANT METASTASIS • M1- DISTANT METASTASIS PRESENT TNM STAGING STAGE O - Tis,N0 ,M0 STAGE IA -T1N0M0 IB - T2N0M0 T1N1M0 TNM STAGING IIA - T3N0M0 T2N1M0 T1N2M0 1IB - T4aN0M0 T3N1M0 T2N2M0 T1N3M0 TNM STAGING 1IIA -T4aN1M0 T3N2M0 T2N3M0 IIIB –T4b N0M0 T4b N1M0 T4a N2 M0 T3 N3 M0 TNM STAGING IIIC - T4bN2M0 T4bN3M0 T4aN3M0 IV Any T Any N M1