COLORECTAL CANCER

DONE BY AON AL-RYALAT

Click to add text

• Epidemiology

• Incidence:∼ 130,000 new cases per year

• Third most common cancer in women and men

• Age: continuous increase in incidence after the age of 50

• Mortality: third leading cause of cancer-related deaths in the US overall

ETOLOGY

• Predisposing factors

• Colorectal adenomas (see colonic polyps)

• Family history

• Hereditary syndromes

• Familial adenomatous polyposis: 100% risk by age 40

• Hereditary nonpolyposis colorectal cancer (HNPCC): 80% progress

to CRC.

PREDISPOSING FACTORS

• Conditions associated with an increased risk of colorectal cancer

• Inflammatory bowel disease (IBD):ulcerative colitis

• and Crohn's disease

• Chronic inflammation → hyperplasia → non-polypoid dysplasia→ neoplasia

• Endocarditis and bacteremia due to Streptococcus gallolyticus is associated with CRC.

• Diet and lifestyle :Smoking-Alcohol consumption -Obesity -Processed meat; high-fat, low-fiber diets

• Older age

It is unclear whether S. gallolyticus is a risk factor for CRC or colonization is promoted by neoplastic lesions in the colon.

PROTECTIVE FACTORS

• Physical activity

• Diet rich in fiber and vegetables and lower in meat

• Long-term use of aspirin and other NSAIDs

•

CLINICAL FEATURES

• Often asymptomatic, particularly during the early stages of disease

• Nonspecific symptoms:constitutional symptoms (weight loss, fever, night sweats), fatigue,

abdominal discomfort

• In general, right-sided tumors chronically bleed, and left sided tumors cause obstruction

Symptoms according to location

• Right-sided carcinomas (10%): cecum and ascending colon

• Iron deficiency anemia

• Melena

• Diarrhea

• Left-sided carcinomas (10%): transverse and descending colon

• Changes in bowel habits (size, consistency, frequency)

• Blood-streaked stools

• Colicky abdominal pain due to obstruction

• Rectum (50%) and sigmoid (30%)

• Hematochezia

• ↓ Stool caliber (pencil-shaped stool)

• Rectal pain

• Tenesmus

• Flatulence with involuntary stool loss

SYMPTOMS ACCORDING TO STAGE OF DISEASE

• Advanced disease

• Palpable abdominal mass

• Intestinal obstruction or perforation

• Metastatic disease: 20% of patients already have distant metastasis on initial diagnosis.

• Liver metastases : abdominal distention, hepatomegaly, ascites

• Lung metastases : dyspnea, cough, hemoptysis, pleural effusion

• Lymphatic spread to mesenteric,para-aortic, and pelvic lymph nodes

PATHOLOGY

• Adenocarcinoma (most common): 95% arise from adenomatous polyps

• Chromosomal instability pathway in colon cancer:The adenoma-carcinoma sequence is the progressive

accumulation of mutations in oncogenes (e.g., KRAS) and tumor suppressor genes (e.g., APC,TP53) that results

in the slow transformation of adenomas into carcinomas.

• APC gene mutation (loss of cellular adhesion and increased cellular proliferation) → KRAS gene mutation (unregulated

cellular signaling and cellular proliferation) →TP53 and DCC gene mutation (malignant transformation

of adenoma to carcinoma)

• Microsatellite instability pathway in colon cancer: due to methylation or mutations in mismatch repair genes

• MLH-1 and MSH-2

• COX-2 overexpression: associated with colorectal cancer. Thus, the possible protective effect of long-term use

of aspirin and other NSAID

Diagnostics

Work-up of colorectal cancer is indicated in symptomatic patients and

asymptomatic patients with abnormalities detected during routine screening.

• Initial work-up

• Digital rectal examination:Up to 10% of cancers are palpable!

• Complete colonoscopy:gold standard

• Complete surveillance of the colon is mandatory!

• If colonoscopy is incomplete → perform double-contrast barium enema

• Apple-core lesion

• In up to 5% of cases, multiple adenocarcinomas are present. A complete colonoscopy is

necessary to rule out additional tumors!

STAGING AND FURTHER TESTS•

DETERMINE THE EXTENT OF LOCAL AND DISTANT DISEASE

• Endorectal ultrasound: determine depth of tumor infiltration

• CT of abdomen, pelvis, and chest

• CXR•

TUMOR MARKER: CARCINOEMBRYONIC ANTIGEN (CEA) SERUM LEVELS PRIOR TO INITIATING TREATMENT

CEA LEVELS ARE MONITORED DURING THE COURSE OF TREATMENT AND THE FOLLOW-UP PERIOD TO MONITOR TREATMENT RESPONSE AND RECURRENCES. CEA LEVELS ARE NOT USED FOR SCREENING PURPOSES.

STAGE

• The stages of colorectal cancer are based on theTNM staging system by the

American Joint Committee for Cancer (AJCC).

AJCC staging (simp

lified)TNM stage

Corresponding

Dukes

classification stage

Description

I Up to T2, N0, M0 A Invasion of submucosa

II Up to T4, N0, M0 B

Invasion of muscularis

propria but no lymph

node involvement

III Any T, N1/N2, M0 C

Invasion of

subserosa or beyond

(e.g., pericolic and

perirectal fat) with no

involvement of other

organs but with lymph

node involvement

IV Any T, any N, M1 D

Invasion of visceral

peritoneum or

adjacent organs

(distant metastasis)

COLORECTAL CANCER IN THE ASCENDING COLON.

HYPODENSE LESION IN THE LIVER AFTER RESECTION OF SIGMOID CANCER

LIVER METASTASES IN COLORECTAL CANCER

PULMONARY METASTASES

PROGNOSIS

• Overall 5-year survival rate: 65%

• Survival rate according to disease stage

• Stage I: 95%

• Stage II:∼ 80%

• Stage III: 60%

• Stage IV: 5–10%

References

• http://emedicine.medscape.com/article/277496-overview#

TREATMENT

• treatment primarily depends on the location of the tumor and theTNM stage.

• Colon cancer

• Curative approach: any primary tumor with or without regional spread;

resectable metastases in the liver and/or lung

• Treatment involves surgical resection and adjuvant chemotherapy.

• Palliative approach: distant metastases beyond the liver and/or lung or if the patient is not

a surgical candidate due to poor general health

• Treatment involves palliative chemotherapy.

• Surgical management

• Colectomy: The extent of the resection depends on the location of the tumor.

• Right hemicolectomy

• Arterial blood supply: ileocolic, right colic, and right branch of the middle colic artery arising from the superior

mesenteric artery

Click to add text

• Extended right hemicolectomy: if the tumor is in the proximal or middle transverse colon

Click to add text

• Left hemicolectomy

• Arterial blood supply: left colic artery arising from the inferior mesenteric artery

Click to add text

• Sigmoid colectomy

Click to add text

• Total abdominal colectomy: indicated for hereditary and multifocal carcinomas

• Regional lymph node dissection (for pathologic staging)

• Resection of resectable metastases in liver and/or lung

RECTAL CANCER

Transanal excision

• Procedure: minimally invasive excision of small superficial tumors

• Indications: early, localized disease (stage I)

• Low anterior resection (LAR)

• Procedure:sphincter-preserving resection of the rectum and sigmoid

• Total mesorectal excision (TME): en bloc excision of the mesorectum, regional lymph nodes, and

vasculature

• Resection 5 cm beyond the proximal margin of the tumor

• Resection > 2 cm beyond the distal margin of well-differentiated tumors or > 5 cm beyond

the distal margin of poorly differentiated tumors

• Reconstruction (e.g., side-to-side anastomosis) and optional diverting ostomy

• Indications: locally advanced disease (Stage III–IV

• Abdominoperineal resection (APR)

• Procedure: resection of the rectum, sigmoid, and anus

• with TME and permanent colostomy

• Indications: last resort if the distal margin to the rectum cancer is < 2–5 cm to the anus

• Palliative procedures include transanal excision or diverting colostomy to facilitate defecation.

• This procedure is not sphincter-preserving

Click to add text

• Follow-up

• Monitor patients for 5 years following the completion of treatment

• Patient history, physical examination, CEA level: every 3–6 months for 3 years, then every 6

months for 2 years

• Elevated CEA warrants further evaluation to determine site of recurrence or metastasis with CT of

the chest and abdomen, PET, and/or colonoscopy.

• Colonoscopy: after surgical resection, then 1 year after surgery, then every 3–5 years

• 85% of recurrences occur within the first three years following treatment!

PREVENTION

• Screening for colorectal cancer and adenomatous polyps is performed in asymptomatic men and

women ≥ 50 years of age.

• Low-risk individuals: several options

• Complete colonoscopy (gold standard): Repeat every 10 years if no polyps or carcinomas are detected.

• Annual fecal occult blood test (FOBT): screening for occult bleeding, which may indicate colorectal cancer

• Sigmoidoscopy every 5 years

• and FOBT every 3 years

• Annual fecal immunochemical testing (FIT)

• CT colonography every 5 years

• High-risk individuals %%%%

• Complete colonoscopy 10 years earlier than the index patient's age at diagnosis or no later than 40 years of age

• %%%%Positive family history of colorectal cancer, hereditary syndromes, personal history of

adenomatous polyps or colorectal cancer

Surveillance following polypectomy

Histology of removed polyp Recommended interval until next control colonoscopy

•Hyperplastic polyp < 10 mm in size in the rectum or

sigmoid10 years

•Low risk adenoma: 1–2 tubular polyps < 10 mm in size and

without intraepithelial neoplasia (IEN)5–10 years

•High risk adenoma

• 3–10 tubular polyps

• 1 polyp ≥ 10 mm

• 1 villous or tubulovillous polyp

• 1 tubular polyp with high-grade dysplasia

3 years

•More than 10 adenomas < 3 years; depends on the case (i.e., family history)