COLORECTAL CANCER · 2020. 11. 12. · PREDISPOSING FACTORS • Conditions associated with an...
Transcript of COLORECTAL CANCER · 2020. 11. 12. · PREDISPOSING FACTORS • Conditions associated with an...
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COLORECTAL CANCER
DONE BY AON AL-RYALAT
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• 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
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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.
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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.
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PROTECTIVE FACTORS
• Physical activity
• Diet rich in fiber and vegetables and lower in meat
• Long-term use of aspirin and other NSAIDs
•
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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
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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
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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
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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
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Diagnostics
Work-up of colorectal cancer is indicated in symptomatic patients and
asymptomatic patients with abnormalities detected during routine screening.
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• 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!
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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.
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STAGE
• The stages of colorectal cancer are based on theTNM staging system by the
American Joint Committee for Cancer (AJCC).
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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)
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COLORECTAL CANCER IN THE ASCENDING COLON.
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HYPODENSE LESION IN THE LIVER AFTER RESECTION OF SIGMOID CANCER
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LIVER METASTASES IN COLORECTAL CANCER
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PULMONARY METASTASES
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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#
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TREATMENT
• treatment primarily depends on the location of the tumor and theTNM stage.
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• 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.
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• 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
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• Extended right hemicolectomy: if the tumor is in the proximal or middle transverse colon
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• Left hemicolectomy
• Arterial blood supply: left colic artery arising from the inferior mesenteric artery
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• Sigmoid colectomy
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• 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
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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
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• 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
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• 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!
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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
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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)