1st Department of Semmelweis University Budapest NEOPLASMS OF THE GASTROINETESTINAL TRACT Prof. Dr....

1st Department of Semmelweis University Budapest

NEOPLASMS OF THE NEOPLASMS OF THE GASTROINETESTINAL GASTROINETESTINAL

TRACTTRACT

Prof. Dr. Ferenc Szalay

Budapest, 2005

Neoplasms of the Gastrointestinal TractNeoplasms of the Gastrointestinal Tract

Npls of GI tract continue to be the most common malignant tumors

EsophagusStomachPancreasLiverBiliary tractSmall bowelColon

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

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

Normal

Barrett’s oesophagus

Barrett’s dysplasiaBarrett’s dysplasiaBarrett’s dysplasiaBarrett’s dysplasia

Columnar cells instead of squamous cells

Adenocarcinoma of esophagus

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

ESOPHAGUSESOPHAGUS

COMPLICATIONS

SilentSymptomatic

Metastatic no serosal liningmetastasize early

to regional lymph nodes

ESOPHAGUSESOPHAGUS

DIAGNOSIS

Double contrast barium

Endoscopy

biopsy - cytology, histology

CT

Endoscopic ultrasonography

Radiographic evaluation in suspected esophageal cancer

Gastroesophageal junction Gastroesophageal junction type II tumorstype II tumors

Esophageal cancer

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)

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

ESOPHAGUSESOPHAGUS

TREATMENT

Surgical resection: cure only in10-30%

Palliation: radiationplastic tube (prosthesis)metal stentdilatation endoscopic

laserthermal

Resected esophageal specimen

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

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

CARCINOMA OF THE STOMACHCARCINOMA OF THE STOMACH

DIAGNOSIS

Upper endoscopy

BIOPSY histology

Endoscopic sonography

Double contrast barium

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%

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

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

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


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)


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

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?

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

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

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


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


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


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

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

Large pedunculated polyp

Pedunculated polyps

Large sessile polyp

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

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

Tubular adenoma of the colon

Tubulovillous adenoma

Percent of adenomas containing invasive cancer

Adenoma size, cm

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

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

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

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

TUMORS OF THE LIVERTUMORS OF THE LIVER

BenignTumor-likeMalignantMetastatic


BenignHemangiomaHepatocellular adenomaFocal nodular hyperplasia (FNH)Biliary truct adenomaIntrahepatic cytadenoma


Tumor-likeSoliter cysts

Polycystic liverEchinococcus cystLiver abscessHaematomaHamartoma


MalignantHepatocellularis carcinomaFibrolamellar carcinomaHepatoblastomaCholangiocarcinomaAngiosarcoma

MetastaticFrom any organ except brain

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

1 cm

Polycystás máj

Májmetastasis különböző megjelenései

1st Department of Semmelweis University Budapest NEOPLASMS OF THE GASTROINETESTINAL TRACT Prof. Dr....

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