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1st Department of Semmelweis University Budapest
NEOPLASMS OF THE NEOPLASMS OF THE GASTROINETESTINAL GASTROINETESTINAL
TRACTTRACT
Prof. Dr. Ferenc Szalay
Budapest, 2005
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Neoplasms of the Gastrointestinal TractNeoplasms of the Gastrointestinal Tract
Npls of GI tract continue to be the most common malignant tumors
EsophagusStomachPancreasLiverBiliary tractSmall bowelColon
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ESOPHAGUSESOPHAGUS
Squamous cell cc.
Adenocarcinoma
INCIDENCE 5/100.000black men 4-5x more comonly affectedmail > femaildramatic regional differencesin certain areas of China: incidence 1:1000adenocarcinoma in western countries
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ETIOLOGY and PATHOGENESIS
Cause of squamous cell cc. is unknownEnviromental factors: tobacco
alcohol abuselye ingestion, hot tearadiationlong term stasis (achalasia)
Adenocarcinoma association with Barrett’s GERDinherited disorder: tylosis
ESOPHAGUSESOPHAGUS
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Normal
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Barrett’s oesophagus
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Barrett’s dysplasiaBarrett’s dysplasiaBarrett’s dysplasiaBarrett’s dysplasia
Columnar cells instead of squamous cells
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Adenocarcinoma of esophagus
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ESOPHAGUSESOPHAGUS
CLINICAL MANIFESTATIONS
Dysphagia 1st solid food2nd liquids
AnorexiaWeight lossRegurgitation aspi ration pneumoniaFistula tracheooesophagealPainHoarsness due to impingement of laryngeal nerveGI bleeding occult iron deficient anemia
massive and fatal if erodes aorta
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ESOPHAGUSESOPHAGUS
COMPLICATIONS
SilentSymptomatic
Metastatic no serosal liningmetastasize early
to regional lymph nodes
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ESOPHAGUSESOPHAGUS
DIAGNOSIS
Double contrast barium
Endoscopy
biopsy - cytology, histology
CT
Endoscopic ultrasonography
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Radiographic evaluation in suspected esophageal cancer
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Gastroesophageal junction Gastroesophageal junction type II tumorstype II tumors
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Esophageal cancer
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AJCC Staging of Esophagus: TNM Staging
Regional lymph nodes (N)Nx Regional lymph nodes cannot be assassedN0 No regional lymph node metastasisN1 Regional lymph node metastasis
Distant metastasis (M)Mx Distant metastasis cannot be assassedM0 No distant metastasisM1 Distant metastasis
Tumors of lower or upper esophagusM1a Metastasis in nonregional lymph nodeM1b Distant metastasis (eg: liver, bone, brain)
Tumors of middle esophagusM1a Not applicableM1b Metastasis in nonregional lymph node or distant metastasis (eg: liver, bone, brain)
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AJCC Staging of Esophagus: TNM Staging
Stage Tumor Node Metastasis
Stage 0 Tis N0 M0Stage I T1 N0 M0
T2 N0 M0Stage IIA T3 N0 M0
T1 N1 M0Stage IIB T2 N1 M0
T3 N1 M0Stage III T4 Any N M0Stage IV Any T Any N M1Stage IV A Any T Any N M1aStage IV B Any T Any N M1b
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ESOPHAGUSESOPHAGUS
TREATMENT
Surgical resection: cure only in10-30%
Palliation: radiationplastic tube (prosthesis)metal stentdilatation endoscopic
laserthermal
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Resected esophageal specimen
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CARCINOMA OF THE STOMACHCARCINOMA OF THE STOMACHINCIDENCE and predisposing factors
Adenocarcinoma > 90% of malignant tumors of the stomach
Since 1940s unexplained decrease in incidenceMarked variation: High rate in Japan,
South America, Eastern Europe
Following emigration very slowly
Helicobacter pyloriDiet high salt and nitratesPernicious anemia - atrophic gastritis
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CARCINOMA OF THE STOMACHCARCINOMA OF THE STOMACHCLINICAL MANIFESTATIONS
Clinical presentation depends on morphologic characteristics: infiltrating or ulcerating size of the tumor presence of gastric outlet obstruction metastatic or nonmetastatic
PainNausea and vomitingAnorexiaIron deficiency anemiaParaneoplastic signs
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CARCINOMA OF THE STOMACHCARCINOMA OF THE STOMACH
DIAGNOSIS
Upper endoscopy
BIOPSY histology
Endoscopic sonography
Double contrast barium
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CARCINOMA OF THE STOMACHCARCINOMA OF THE STOMACH
TREATMENT and PROGNOSIS
Surgery only 1/3 are resectable for cure
Curative for early gastric cancer
Survival for most patients< 5%
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LYMPHOMA OF THE STOMACHLYMPHOMA OF THE STOMACH
Relatively uncommon<15% of gastric malignancies2% of all lymphomasmost frequent extranodal site for lymphomaincreased 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
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GASTRIC (NONLYMPHOID) SARCOMA OF GASTRIC (NONLYMPHOID) SARCOMA OF THE STOMACHTHE 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
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CARCINOMA OF THE COLONCARCINOMA OF THE COLON
INCIDENCE and predisposing factors
3rd most comon cc. in men, 2nd in women3rd most common cause of cancer deathCRC is 15% of all malignant tumorsMore comon in developed countriesEmigrants get the risk characteristic for new enviroment
Role of dietGenetic factors
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CARCINOMA OF THE COLONCARCINOMA OF THE COLON
RISK FACTORS
Increasing ageInflammatory bowel disease (UC)Personal history of colon cancer or adenomaFamily history of colon cancerFamilial polyposis syndromes (adenomatous polyps)
History of breast or female genital cancerPeutz-Jeghers syndrome (hamartomas)
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CARCINOMA OF THE COLONCARCINOMA OF THE COLON
ETIOLOGY and PATHOGENESIS
Enviromental factorsDiet low in fiberDiet high in animal fat and proteinToxic bile acids (role of colonic bacteria)Role of different factors:
calcium, vitamin-DseleniumCOX system
Unknown ?? OncogensGenetic factors
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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 studyFried 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?
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Gene ChromosomeSporadic tumors with alterations,
%Class Function
K-ras 12 50 ProtooncogeneSignal transduction
APC 5 60 Tumor supressor ?Cell adhesion
DCC 18 70 Tumor supressor ?Cell adhesion
p53 17 75 Tumor supressorCell cycle control (G1/S arrest)
hMSH2 2DNA Mismatch repair
Maintains fidelity of DNA replication
hMLH1 3DNA Mismatch repair
Maintains fidelity of DNA replication
Genes altered in colon cancerGenes altered in colon cancer
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CARCINOMA OF THE COLONCARCINOMA OF THE COLONCLINICAL MANIFESTATIONS
Few early warning signsDepend on location, size, bleeding tendencyGI blood loss occult blood
melaenahematochezia
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
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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
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CARCINOMA OF THE COLONCARCINOMA OF THE COLON
DIAGNOSIS
History:Should be suspected over age 40 with symptoms of GI blood loss, etc.
Digital rectal examinationDouble-contrast barium enemaColonoscopyBiopsyCarcinoembrionic antigen (CEA) useful in follow-up surgery to detect recurrence
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CARCINOMA OF THE COLONCARCINOMA OF THE COLON
TREATMENT and PROGNOSIS
Surgery remove tumor and adjacent colon and mesenterypreoperative CT to exclude synchronous colon tu.
and metastasesprocedure depends on location of the tumorsave sphyncter ani if possible
RadiationChemotherapy (5-FU, irinotecan, cysplatin)
PalliativeFollow-up after surgery
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CARCINOMA OF THE COLONCARCINOMA OF THE COLON
SCREENING AND PREVENTION
Link between adenomatous polyps and cancer !
Testing for occult fecal blood over age 40-50 yColonoscopy over age 50 yColonoscopy in high risk population
Diet
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POLYPS OF THE GASTROINTESTINAL TRACTPOLYPS 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 multiplesporadic or familialpedunculated (stalk) or sessile (flat base)
neoplastic or non-neoplasticbenign or malignant
May occure enywhere throughout the GI tract
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Large pedunculated polyp
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Pedunculated polyps
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Large sessile polyp
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POLYPS OF THE GASTROINTESTINAL TRACTPOLYPS 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
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POLYPS OF THE COLONPOLYPS OF THE COLON
Neoplastic PolypsBening adenomatous polyps (tubular, mixed or villous)
Random occurencesFamilial- familial polyposis of the colon
Gardner’s syndromeTurcot’s syndrome, family cancer syndrome
Malignant polyps- carcinomatous changes, in situ or invasive
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Tubular adenoma of the colon
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Tubulovillous adenoma
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Tubulovillous adenoma
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Percent of adenomas containing invasive cancer
Adenoma size, cm
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POLYPS OF THE COLONPOLYPS OF THE COLON
Neoplastic PolypsBening adenomatous polyps (tubular, mixed or villous)
Random occurencesFamilial- familial polyposis of the colon
Gardner’s syndromeTurcot’s syndrome, family cancer syndrome
Malignant polyps- carcinomatous changes, in situ or invasive
Non-Neoplastic PolypsInflammatory „pseudopolyps”Peutz-Jeghers syndrome - hamartomasMucosal polyps with normal epitheliumJuvenile polyps
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Hereditary nonpolyposis colorectal Hereditary nonpolyposis colorectal cancer cancer
Three or more relatives with colorectal cancer (one must be first-degree relative of other two)
Colorectal cancer involving at least two generations
One or more colorectal cancer cases before age 50
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CharacteristicsCharacteristics HNPCCHNPCC SporadicSporadic
Mean age at diagnosis, y 44.6 67
Multiple colon cancers, % 34.5 4-11
Synchronous 18.1 3-6
Metachronous 24.3 1-5
Proximal location, % 72.3 35
Excess malignancies at other sites Yes No
Mucinous and poorly differentiated cancers
Common Infrequent
RER + % 79 17
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Cutaneous manifestations of gastrointestinal tract polyposis syndromes
Familial adenomatous polyposis and Gardner's syndrome Epidermoid cysts Desmoid tumors Pigmented lesionsPeutz-Jeghers syndrome Mucocutaneous pigmentationMultiple hamartoma syndrome (Cowden's disease) Trichilemmomas Oral mucosal papillomatosis Cowden's fibroma Acral keratosesMuir-Torre syndrome Sebaceous hyperplasia Sebaceous adenomas Sebaceous epithelioma Sebaceous carcinoma Multiple keratoacanthomas
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TUMORS OF THE LIVERTUMORS OF THE LIVER
BenignTumor-likeMalignantMetastatic
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TUMORS OF THE LIVERTUMORS OF THE LIVER
BenignHemangiomaHepatocellular adenomaFocal nodular hyperplasia (FNH)Biliary truct adenomaIntrahepatic cytadenoma
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TUMORS OF THE LIVERTUMORS OF THE LIVER
Tumor-likeSoliter cysts
Polycystic liverEchinococcus cystLiver abscessHaematomaHamartoma
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TUMORS OF THE LIVERTUMORS OF THE LIVER
MalignantHepatocellularis carcinomaFibrolamellar carcinomaHepatoblastomaCholangiocarcinomaAngiosarcoma
MetastaticFrom any organ except brain
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PBC talaján, a diagnózis után 18 évvel kialakult HCC
A szérum AFP értéke a halál előtt 3480 ng/ml volt (norm: 0-15 ng/ml)
Immunhisztológiai vizsgálat: a piros foltok jelzik az AFP pozitivitást
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1 cm
Polycystás máj
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Májmetastasis különböző megjelenései