Transcript hereditary nonpolyposis colorectal

Colorectal carcinoma
Dr.Mohammadzadeh
Epidemiology (Risk Factors)
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Aging
Hereditary Risk Factors
Environmental and Dietary Factors
Inflammatory Bowel Disease
Other Risk Factors
Genetic Defects
Polyps
• Any projection from the surface of the
intestinal mucosa regardless of its histologic
nature
• adenoma–carcinoma sequence :
The majority of colorectal carcinomas
evolve from adenomatous polyps
Types of Colorectal polyps
• Neoplastic (tubular adenoma, villous
adenoma, tubulovillous adenomas)
• Hamartomatous (juvenile, Peutz-Jeghers,
Cronkite-Canada)
• Inflammatory (pseudopolyp, benign lymphoid
polyp)
• Hyperplastic
Neoplastic Polyps
• Adenomatous polyps are common, occurring in
up to 25% of the population older than 50 years
of age
• The risk of malignant degeneration is related to
both the size and type of polyp.
• Tubular adenomas are associated with
malignancy in only 5% of cases, whereas villous
adenomas may harbor cancer in up to 40%.
Tubulovillous adenomas are at intermediate risk
(22%).
• Polyps may be pedunculated or sessile.
• Most pedunculated polyps are amenable to
colonoscopic snare excision. Removal of
sessile polyps often is more challenging
• Complications of polypectomy include
perforation and bleeding
Hamartomatous Polyps (Juvenile
Polyps)
• In contrast to adenomatous polyps,
hamartomatous polyps (juvenile polyps)
usually are not premalignant.
• Bleeding is a common symptom and
intussusception and/or obstruction may occur.
Juvenile Polyposis
• Familial juvenile polyposis
• Peutz-Jeghers syndrome
• Cronkite-Canada syndrome
• Cowden syndrome
Inflammatory Polyps (Pseudopolyps)
• Inflammatory polyps occur most commonly in
the context of inflammatory bowel disease
• May also occur after amebic colitis, ischemic
colitis, and schistosomal colitis.
• These lesions are not premalignant
Hyperplastic Polyps
• Hyperplastic polyps are extremely common in
the colon.
• These polyps usually are small (<5 mm) and
show histologic characteristics of hyperplasia
without any dysplasia.
• They are not considered premalignant
• Hyperplastic polyposis
Inherited Colorectal Carcinoma
• Familial Adenomatous Polyposis
• Attenuated FAP
• Hereditary Nonpolyposis Colon Cancer (Lynch
Syndrome)
• Familial Colorectal Cancer
Familial Adenomatous Polyposis
• autosomal dominant
• about 1% of all colorectal adenocarcinomas
• The genetic abnormality in FAP is a mutation in the APC gene,
located on chromosome 5q.
• Once the diagnosis of FAP has been made and polyps are
developing, treatment is surgical.
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Four factors affect the choice of operation: age of the patient;
presence and severity of symptoms; extent of rectal polyposis; and
presence and location of cancer or desmoid tumors.
Attenuated FAP
• Patients present later in life with fewer polyps
(usually 10 to 100) dominantly located in the
right colon
• Colorectal carcinoma develops in more than
50% of these patients, but occurs later
(average age 55 years).
Lynch Syndrome(HNPCC)
• HNPCC (or Lynch syndrome) is more common
than FAP, but is still extremely rare (1 to 3%).
• Approximately 70% of affected individuals will
develop colorectal cancer (average age: 40 to 45
years).
• Cancers appear in the proximal colon more often
than in sporadic colorectal cancer and have a
better prognosis regardless of stage.
Familial Colorectal Cancer
• Nonsyndromic familial colorectal cancer accounts
for 10 to 15% of patients with colorectal cancer
• The lifetime risk of colorectal cancer in a patient
with no family history of this disease (averagerisk population) is approximately 6%, but rises to
12% if one first-degree relative is affected and to
35% if two first-degree relatives are affected.
Routes of Spread
Clinical Presentation
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Nonspecific and generally develop when the cancer is locally advanced.
• The classic first symptoms are a change in bowel habits and rectal
bleeding.
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Abdominal pain, bloating, and other signs of obstruction typically occur
with larger tumors .
• Because of the caliber of the bowel and the consistency of the stool, leftsided tumors are more likely to cause obstruction than are right-sided
tumors.
• Rectal tumors may cause bleeding, tenesmus, and pain.
• unexplained anemia, weight loss, or poor appetite
Stage-Specific Therapy
• Stage 0 (Tis, N0, M0) :
these polyps should be excised completely
and pathologic margins should be free of
dysplasia.
• In cases where the polyp cannot be removed
entirely, a segmental resection is
recommended
Stage I: The Malignant Polyp (T1, N0,
M0)
• Invasive carcinoma in the head of a pedunculated polyp
with no stalk involvement carries a low risk of metastasis
(<1%) and may be completely resected endoscopically.
• However, lymphovascular invasion, poorly differentiated
histology, or tumor within 1 mm of the resection margin
greatly increases the risk of local recurrence and metastatic
spread. Segmental colectomy is then indicated.
• Invasive carcinoma arising in a sessile polyp extends into
the submucosa and is usually best treated with segmental
colectomy
Stages I and II: Localized Colon
Carcinoma (T1–3, N0, M0)
• The majority of patients with stages I and II colon
cancer will be cured with surgical resection
• Adjuvant chemotherapy does not improve
survival in these patients
• Adjuvant chemotherapy has been suggested for
selected patients with stage II disease (young
patients, tumors with "high-risk" histologic
findings)
Stage III: Lymph Node Metastasis
(Tany, N1, M0)
Patients with lymph node involvement are at
significant risk for both local and distant
recurrence, and adjuvant chemotherapy has
been recommended routinely in these
patients
Stage IV: Distant Metastasis (Tany,
Nany, M1)
• Survival is extremely limited in stage IV colon
carcinoma
• Of patients with systemic disease, approximately
15% will have metastases limited to the liver. Of
these, 20% are potentially resectable for cure
• Metastasis of the lung, occurring in
approximately 20% of patients and 1-2% will be
resectable