00:00 Colorectal Carcinoma Eugen Divjak Mentor: A. Žmegač Horvat.

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Colorectal Carcinoma

Eugen DivjakMentor: A. Žmegač Horvat

Intestinal tumorsNon-neoplastic Polyps

Hyperplastic polyps

Hamartomatous polyps

Juvenile polyps

Peutz-Jeghers polyps

Inflammatory polyps

Lymphoid polyps

Neoplastic Epithelial Lesions

Benign polyps

Adenomas

Malignant lesions

Adenocarcinoma

Squamous cell carcinoma of the anus

Other Tumors

Gastrointestinal stromal tumors

Carcinoid tumor

Lymphoma

Epithelial tumors of the intestines:major cause of morbidity and mortality worldwide

Colon, including rectum:host to more primary neoplasms than any other organ in the body

Adenocarcinoma

98% of all cancers in large intestine almost always arise in adenomatous polyps,

generally curable by resection

Epidemiology

peak incidence: 60 to 70 years of age < 20% cases before age of 50 adenomas – presumed precursor lesions for

most tumors males affected ≈ 20% more often than

females

Epidemiology

worldwide distribution highest incidence rates in United States,

Canada, Australia, New Zealand, Denmark, Sweden, and other developed countries

Etiology

genetic influences: preexisting ulcerative colitis or polyposis

syndrome hereditary nonpolyposis colorectal cancer

syndrome (HNPCC, Lynch syndrome) → germ-line mutations of DNA mismatch repair genes

Etiology

environmental influences: dietary practices

low content of unabsorbable vegetable fiber corresponding high content of refined carbohydrates high fat content decreased intake of protective micronutrients

(vitamins A, C, and E) use of Aspirin® and other NSAIDs: protective

effect against colon cancer? cyclooxygenase-2 & prostaglandin E2

Carcinogenesis

chromosome instability pathway

Carcinogenesis

mismatch repair (microsatellite instability) pathway

Morphology

25% of colorectal carcinomas: in cecum or ascending colon

similar proportion: in rectum and distal sigmoid

25%: in descending colon and proximal sigmoid

remainder scattered elsewhere multiple carcinomas present → often at

widely disparate sites in the colon

Morphology

all colorectal carcinomas begin as in situ lesions tumors in the proximal colon: polypoid, exophytic

masses that extend along one wall of the cecum and ascending colon

Morphology

in the distal colon: annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumen

both forms of neoplasm eventually penetrate the bowel wall and may appear as firm masses on the serosal surface

Morphology all colon carcinomas - microscopically similar almost all - adenocarcinomas range from well-differentiated to undifferentiated,

frankly anaplastic masses many tumors produce mucin secretions dissect through the gut wall, facilitate

extension of the cancer and worsen the prognosis cancers of the anal zone are predominantly

squamous cell in origin

Clinical Features may remain asymptomatic for years symptoms develop insidiously cecal and right colonic cancers:

fatigue weakness iron deficiency anemia

left-sided lesions: occult bleeding changes in bowel habit crampy left lower quadrant discomfort

anemia in females may arise from gynecologic causes, but it is a clinical maxim that iron deficiency anemia in an older man means gastrointestinal cancer until proved otherwise

Clinical Features spread by direct extension into

adjacent structures and by metastasis through lymphatics and blood vessels

favored sites for metastasis: regional lymph nodes liver lungs bones other sites including serosal

membrane of the peritoneal cavity

carcinomas of the anal region → locally invasive, metastasize to regional lymph nodes and distant sites

TNM Staging of Colon Cancer

Tumor (T)T0 = none evidentTis = in situ (limited to mucosa)T1 = invasion of lamina propria or submucosaT2 = invasion of muscularis propriaT3 = invasion through muscularis propria into

subserosa or nonperitonealized perimuscular tissue

T4 = invasion of other organs or structures

Lymph Nodes (N)0 = none evident1 = 1 to 3 positive pericolic nodes2 = 4 or more positive pericolic nodes3 = any positive node along a named blood vessel

Distant Metastases (M)0 = none evident1 = any distant metastasis

5-Year Survival RatesT1 = 97%T2 = 90%T3 = 78%T4 = 63%Any T; N1; M0 = 66%Any T; N2; M0 = 37%Any T; N3; M0 = data not availableAny M1 = 4%

Clinical Features detection and diagnosis:

digital rectal examination fecal testing for occult blood loss barium enema, sigmoidoscopy

and colonoscopy confirmatory biopsy computed tomography and other

radiographic studies serum markers (elevated blood

levels of carcinoembryonic antigen)

molecular detection of APC mutations in epithelial cells, isolated from stools

tests under development: detection of abnormal patterns of methylation in DNA isolated from stool cells

Therapy

chemotherapy radiotherapy photodynamic therapy radical surgery gene therapy

True or false?

98% of all cancers in the large intestine are adenocarcinomas.

Use of Aspirin® and other NSAIDs may cause development of colon cancer.

Chromosome instability and the mismatch repair are two carcinogenesis pathways.

Tumors in the proximal colon tend to be annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumen, while those in the distal colon tend to grow as polypoid, exophytic masses.

Colorectal carcinoma may remain asymptomatic for years.

References: http://www.liebertonline.com/doi/abs/10.1089/pho.2008.2238 http://clincancerres.aacrjournals.org/cgi/content/abstract/5/9/2359 Elsevier. Kumar et al: Robbins Basic Pathology 8e