Scribd
Upload
134 views25 pages

Pathophysiology: Rectal Carcinoma

Rectal carcinoma is the second most common cause of cancer death. Risk factors include aging over 50, diet high in meat/fried foods and low in vegetables, and certain genetic conditions. Molecular changes in genes like KRAS, APC, MYH and PT53 lead to abnormal cell growth and potentially cancer. This patient presents with constipation, thin stools, and intermittent abdominal pain. Further workup is needed to stage the tumor based on tumor size, lymph node involvement, and metastasis.

Uploaded by

Cristina Cristina
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
134 views25 pages

Pathophysiology: Rectal Carcinoma

Rectal carcinoma is the second most common cause of cancer death. Risk factors include aging over 50, diet high in meat/fried foods and low in vegetables, and certain genetic conditions. Molecular changes in genes like KRAS, APC, MYH and PT53 lead to abnormal cell growth and potentially cancer. This patient presents with constipation, thin stools, and intermittent abdominal pain. Further workup is needed to stage the tumor based on tumor size, lymph node involvement, and metastasis.

Uploaded by

Cristina Cristina
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 25

Pathophysiology

Rectal Carcinoma

Sources: Harrison's Principles of Internal Medicine, 20th Edition (Part 4 Sec 1, Chapter 77); &
Schwartz’s_11th_Edition (Chapter 29)
RECTAL CARCINOMA
Incidence
• Cancer of the large bowel is second only to
lung cancer as a cause of cancer death
• The incidence rate has decreased
significantly during the past 25 years, likely
due in large part to enhanced and more
compliantly followed screening practices
• mortality rates have decreased by ~25%,
resulting largely from earlier detection and
improved treatment.
RISK FACTORS

AGE DIET HEREDITARY


FACTORS

GENETIC GENETIC
DEFECTS PATHWAYS

Molecular changes/effect
of normal colorectal
epithelium

Growth and mutation of a


nodular mass in the rectum

RECTAL
CARCINOMA
Source: Harrison's Principles of Internal Medicine, 20th Edition
Etiology and Risk Factors
• Aging:
Aging is the dominant risk factor for
colorectal cancer, with incidence rising
steadily after age 50 years.
More than 90% of cases diagnosed are in
people older than age 50 years.
• Diet:
prefers more on meat and fried foods
than vegetables and drinks soda (coke)
every meal
Etiology and Risk Factors
• Hereditary Factors:
 no heredofamilial disease of cancers on both parents;
Paternal: Hypertension, Maternal: Diabetes Mellitus
• No history of Irritable Bowel Disease
• Non-smoker
• Genetic factors:
- Familial adenomatous polyposis
- HNPCC
- Lynch syndrome I & II
- Turcot's syndrome
- Peutz-jeghers syndrome
Clinical Features:
• Constipation
• Irregualar bowel movement
• Tenesmus
• Stools thinner than normal
• Intermittent abdominal pain
Clinical Features:

• Unexplained weight loss


• Anemia
• Rectal bleeding
• Diarrhea
Molecular Pathogenesis
• Most colorectal cancers, regardless of etiology,
arise from adenomatous polyps.
• A polyp is a grossly visible protrusion from the
mucosal surface and may be classified
pathologically as:
nonneoplastic hamartoma (e.g., juvenile
polyp)
hyperplastic mucosal proliferation
(hyperplastic polyp)
adenomatous polyp
Molecular Pathogenesis
• Only adenomas are clearly premalignant, and
only a minority of adenomatous polyps evolve
into cancer.
• Adenomatous polyps may be found in the
colons of:
~30% of middle-aged (45 to 65 years old) and
~50% of elderly people (65 years old above)
• However, <1% of polyps ever become
malignant.
Molecular Pathogenesis
• A number of molecular changes are
noted in adenomatous polyps and
colorectal cancers that are thought
to reflect a multistep process in the
evolution of normal colonic mucosa
to life-threatening invasive
carcinoma.
Genetic Defects
• K-Ras mutations - may cause activation
of oncogenes
• APC gene mutation - inactivation of
tumor suppressor genes
• MYH gene mutation
• p53 mutation
• PTEN deletion
Genetic Defects
• One of the most commonly involved
genes in colorectal cancer is K-ras.
• Mutation of KRAS results in an inability
to hydrolyze GTP
• Leaving the G-protein permanently in the
active form. It is thought that this then
leads to uncontrolled cell division.
Genetic Defects
• The APC gene is a tumor suppressor gene.
Mutations in both alleles are necessary to
initiate polyp formation.

• Defects in the APC gene were first described


in patients with Familial Adenomatous
Polyposis (FAP).
Genetic Defects

• MYH mutations have been associated with an


AFAP phenotype in addition to sporadic
cancers. Unlike APC gene mutations that are
expressed in an autosomal dominant pattern,
the requirement for biallelic mutation in MYH
results in an autosomal recessive pattern of
inheritance.
Genetic Defects
• Deletion of the tumor suppressor
phosphatase and tensin homolog (PTEN)
appears to be involved in a number of
hamartomatous polyposis syndromes.
• Deletions in PTEN have been identified in
juvenile polyposis, Peutz-Jeghers syndrome,
Cowden’s syndrome, and PTEN hamartoma
syndrome.
Genetic Pathway
• The mutations involved in colorectal cancer
pathogenesis and progression are now
recognized to accumulate via one of three
major genetic pathways:
the loss of heterozygosity (LOH; chromosomal
instability) pathway,
the microsatellite instability (MSI) pathway, and
the CpG island methylation (CIMP; serrated
methylated) pathway.
AMERICAN JOINT COMMITTEE ON CANCER STAGING

COLON AND RECTUM CANCER


STAGING
Impression

RENAL CARCNOMA,
Stage II (T3-4, N0, M0)

You might also like