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NEOPLASMS OF THE GASTROINETESTINAL TRACT. Prof. Dr. Ferenc Szalay. 1st Department of Semmelweis University Budapest. Budapest, 2005. Neoplasms of the Gastrointestinal Tract. Npls of GI tract continue to be the most common malignant tumors. Esophagus Stomach Pancreas Liver Biliary tract
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NEOPLASMS OF THE GASTROINETESTINAL TRACT Prof. Dr. Ferenc Szalay 1st Department of Semmelweis University Budapest Budapest, 2005
Neoplasms of the Gastrointestinal Tract Npls of GI tract continue to be the most commonmalignant tumors Esophagus Stomach Pancreas Liver Biliary tract Small bowel Colon
ESOPHAGUS Squamous cell cc. Adenocarcinoma INCIDENCE 5/100.000 black men 4-5x more comonly affected mail > femail dramatic regional differences in certain areas of China: incidence 1:1000 adenocarcinoma in western countries
ESOPHAGUS ETIOLOGY and PATHOGENESIS Cause of squamous cell cc. is unknown Enviromental factors: tobacco alcohol abuse lye ingestion, hot tea radiation long term stasis (achalasia) Adenocarcinoma association with Barrett’s GERD inherited disorder: tylosis
Barrett’s dysplasia Columnar cells instead of squamous cells
ESOPHAGUS CLINICAL MANIFESTATIONS Dysphagia 1st solid food 2nd liquids Anorexia Weight loss Regurgitation aspi ration pneumonia Fistulatracheooesophageal Pain Hoarsness due to impingement of laryngeal nerve GI bleeding occult iron deficient anemia massive and fatal if erodes aorta
ESOPHAGUS COMPLICATIONS Silent Symptomatic Metastatic no serosal lining metastasize early to regional lymph nodes
ESOPHAGUS DIAGNOSIS Double contrast barium Endoscopy biopsy - cytology, histology CT Endoscopic ultrasonography
AJCC Staging of Esophagus: TNM Staging Regional lymph nodes (N) Nx Regional lymph nodes cannot be assassed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant metastasis (M) Mx Distant metastasis cannot be assassed M0 No distant metastasis M1 Distant metastasis Tumors of lower or upper esophagus M1a Metastasis in nonregional lymph node M1b Distant metastasis (eg: liver, bone, brain) Tumors of middle esophagus M1a Not applicable M1b Metastasis in nonregional lymph node or distant metastasis (eg: liver, bone, brain)
AJCC Staging of Esophagus: TNM Staging Stage Tumor Node Metastasis Stage 0 Tis N0 M0 Stage I T1 N0 M0 T2 N0 M0 Stage IIA T3 N0 M0 T1 N1 M0 Stage IIB T2 N1 M0 T3 N1 M0 Stage III T4 Any N M0 Stage IV Any T Any N M1 Stage IV A Any T Any N M1a Stage IV B Any T Any N M1b
ESOPHAGUS TREATMENT Surgical resection: cure only in10-30% Palliation: radiation plastic tube (prosthesis) metal stent dilatation endoscopic laser thermal
CARCINOMA OF THE STOMACH INCIDENCE and predisposing factors Adenocarcinoma > 90% of malignant tumors of the stomach Since 1940s unexplained decrease in incidence Marked variation: High rate in Japan, South America, Eastern Europe Following emigration very slowly Helicobacter pylori Diet high salt and nitrates Pernicious anemia - atrophic gastritis
CARCINOMA OF THE STOMACH CLINICAL MANIFESTATIONS Clinical presentation depends on morphologic characteristics: infiltrating or ulcerating size of the tumor presence of gastric outlet obstruction metastatic or nonmetastatic Pain Nausea and vomiting Anorexia Iron deficiency anemia Paraneoplastic signs
CARCINOMA OF THE STOMACH DIAGNOSIS Upper endoscopy BIOPSY histology Endoscopic sonography Double contrast barium
CARCINOMA OF THE STOMACH TREATMENT and PROGNOSIS Surgery only 1/3 are resectable for cure Curative for early gastric cancer Survival for most patients< 5%
LYMPHOMA OF THE STOMACH Relatively uncommon <15% of gastric malignancies 2% of all lymphomas most frequent extranodal site for lymphoma increased in frequency durint the past 25 ys Non-Hodgkin’s lymphoma (vast majority) Hodgkin’s lymphoma is uncommon MALT(mucosa associated lymphoid tissue) - H.p. Treatment: Subtotal gastrectomy, combination chemotherapy, Helicobacter pylori eradication
GASTRIC (NONLYMPHOID) SARCOMA OF THE STOMACH Leiomyosarcoma GIST (Gastrointestinal stromal tumor) 1-3% of gastric npls. All such tumors should be analyzed for mutation in the c-kit receptor GISTs are unresponsive to conventional chemotherapy 50% respond to imatinib mesylate (Gleevec), a selective inhibitor of the c-kit tyrosinase kinase
CARCINOMA OF THE COLON INCIDENCE and predisposing factors 3rd most comon cc. in men, 2nd in women 3rd most common cause of cancer death CRC is 15% of all malignant tumors More comon in developed countries Emigrants get the risk characteristic for new enviroment Role of diet Genetic factors
CARCINOMA OF THE COLON RISK FACTORS Increasing age Inflammatory bowel disease (UC) Personal history of colon cancer or adenoma Family history of colon cancer Familial polyposis syndromes (adenomatous polyps) History of breast or female genital cancer Peutz-Jeghers syndrome (hamartomas)
CARCINOMA OF THE COLON ETIOLOGY and PATHOGENESIS Enviromental factors Diet low in fiber Diet high in animal fat and protein Toxic bile acids (role of colonic bacteria) Role of different factors: calcium, vitamin-D selenium COX system Unknown ?? Oncogens Genetic factors
Low fiber→ High concentration of gut bile acids (low dilution and prolonged contact through lack of bulk) and fecal mutagens / carcinogensis High concentration of bile and metabolits → Promoting effect in colon carcinogenesis Mechanisms under study Fried food → Mutagens → Colon carcinogenesis? Role of fecal flora? Role of micronutrients (vitamins, minerals, antioxidants) and different types of fiber in production and metabolism of carcinogens, bile acids, promoters? Specific role of calcium (formation of insoluable calcium phosphate / bile acids? Direct effect on proliferation?) Mechanisms of promotion?
CARCINOMA OF THE COLON CLINICAL MANIFESTATIONS Few early warning signs Depend on location, size, bleeding tendency GI blood loss occult blood melaena hematochezia Alteration of bowel habits (left sided or distal tumors) Owerflow diarrhea (severe but incomplete obstruction) Abdominal pain (uncommon, obstuction related) Weight loss, anorexia (nonspecific, appear late) Perforation, malignant ascites, liver metastasis
Colonic obstruction from a carcinoma of the transverse colon Dilated small and large bowel proximal to the lesion Collapsed bowel distal to the obstructing carcinoma
CARCINOMA OF THE COLON DIAGNOSIS History:Should be suspected over age 40 with symptoms of GI blood loss, etc. Digital rectal examination Double-contrast barium enema Colonoscopy Biopsy Carcinoembrionic antigen (CEA) useful in follow-up surgery to detect recurrence
CARCINOMA OF THE COLON TREATMENT and PROGNOSIS Surgery remove tumor and adjacent colon and mesentery preoperative CT to exclude synchronous colon tu. and metastases procedure depends on location of the tumor save sphyncter ani if possible Radiation Chemotherapy (5-FU, irinotecan, cysplatin) Palliative Follow-up after surgery
CARCINOMA OF THE COLON SCREENING AND PREVENTION Link between adenomatous polyps and cancer ! Testing for occult fecal blood over age 40-50 y Colonoscopy over age 50 y Colonoscopy in high risk population Diet
POLYPS OF THE GASTROINTESTINAL TRACT Overgrowth of tissue, usually of epithelial cells, that arises from the mucosal surface and extends into the lumen of the GI tract single or multiple sporadic or familial pedunculated (stalk) or sessile (flat base) neoplastic or non-neoplastic benign or malignant May occure enywhere throughout the GI tract
POLYPS OF THE GASTROINTESTINAL TRACT INCIDENCE Adenomatous colonic polyps are very comon Increase with age 50 year-old 20% chance 70 year-old 40% chance Patients with one polyp have higher frequency of synchronous P. greater potential for additional P. over time
POLYPS OF THE COLON Neoplastic Polyps Bening adenomatous polyps (tubular, mixed or villous) Random occurences Familial- familial polyposis of the colon Gardner’s syndrome Turcot’s syndrome, family cancer syndrome Malignant polyps- carcinomatous changes, in situ or invasive
Percent of adenomas containing invasive cancer Adenoma size, cm
POLYPS OF THE COLON Neoplastic Polyps Bening adenomatous polyps (tubular, mixed or villous) Random occurences Familial- familial polyposis of the colon Gardner’s syndrome Turcot’s syndrome, family cancer syndrome Malignant polyps- carcinomatous changes, in situ or invasive Non-Neoplastic Polyps Inflammatory „pseudopolyps” Peutz-Jeghers syndrome - hamartomas Mucosal polyps with normal epithelium Juvenile polyps