Screening For Colorectal

Malignancy
&
Familial Colorectal Carcinoma

Amir
Sayrah
Amirul
Ain
Shaznain
Roshini
 INTRODUCTION
• Colorectal carcinoma (CRC) is the second most common
cancer in Malaysia (12.3%) as reported in Malaysian National
Cancer Registry Report 2007-2011.
• According to National Cancer Patient Registry on Colorectal
Cancer 2008-2013, the overall incidence rate for CRC was
21.3 cases per 100,000 population.
• Age-adjusted incidence rate was 1.33 times higher among
male than female.
• The incidence was highest in Chinese followed by Malay and
Indian.
• Overall mortality rate was 9.8 cases per 100,000 population
and age-adjusted mortality rate was 1.42 times higher in
male than female.
 Anatomic Location of CRC

• Cecum 14 %
• Ascending colon 10 %
• Transverse colon 12 %
• Descending colon 7%
• Sigmoid colon 25 %
• Rectosigmoid junct. 9%
• Rectum 23 %
 WHO Classification of CRC
• Adenocarcinoma in situ / severe dysplasia

• Adenocarcinoma

• Mucinous (colloid) adenocarcinoma (>50% mucinous)

• Signet ring cell carcinoma (>50% signet ring cells)

• Squamous cell (epidermoid) carcinoma

• Adenosquamous carcinoma

• Small-cell (oat cell) carcinoma

• Medullary carcinoma

• Undifferentiated Carcinoma
Colon cancers result from a series of pathologic changes that
transform normal epithelium into invasive carcinoma. Specific
genetic events, shown by vertical arrows, accompany this
multistep process.
 Pathogenesis
• Development is a multistep process where in carcinomas arise from benign adenomas.
• The mucosal epithelium progresses through a series of molecular and cellular events that
lead to altered proliferation, cellular accumulation, and glandular disarray leading to the
formation of adenomatous polyps.
• Further genetic alteration results in higher degrees of cellular atypia and glandular
disorganization (dysplasia) , which may evolve to a carcinoma.
• The adenoma-to-carcinoma sequence is always associated with genetic changes, even in
sporadic colon cancers .
• Sporadic polyps and cancers are associated with multiple somatic mutations contributed
by environmental insults.
• Genetic changes that lead to development of adenomas include:
– Alteration in proto-oncogenes

– Loss of tumor suppressor gene : In more than 75% of cases , stepwise tumor
progression is associated with loss of tumor suppressor gene designated D C C
(deleted in colorectal cancer) on chromosome 1 8q- (maintains normal cell-cell
adhesive interactions) .

– Deletions of chromosome 1 7p involving the p-53 tumor suppressor gene

– Abnormalities of genes involved in DNA repair

History and PE
 Focused history
• Age, sex , race – age >50 male predominace, Chinese>malay>in dian

• Diet hx – low fibre food, increased intake of refined carbohydrates, fat

diet, red meat

• Social lifestyle hx- smoking, alcohol

• Past medical hx – chlecyctectomy , hx of colon Ca, ovarian and uterine Ca,

IBD, Pre cancerous conditions-adenomatous polyps/post polypectomy

• Familial syndromes such as:

• Heriditary non polyposis colorectal Ca , Familial adenomatous polyps ,
Gardner’s and Turcot sx.
• For rectal bleeding: colour, location

• For altered bowel habit: alternating constipation

and diarrhoea

• Perianal symptoms (lump, pruritus, pain,

discharge)

• Symptoms of anaemia (look for causes)

 Presence of any of the following signs
or symptoms:
• per rectal bleeding
• mucoid stool
• tenesmus
• constipation
• anaemia
• altered bowel habits
• palpable abdominal mass
• palpable anorectal mass
• loss of weight or appetite
• abdominal discomfort
• perianal symptoms
 Right sided lesion-
• Asymptomatic until advanced stage
• Chronic low grade per rectal bleeding
• Usually no obstructive symptoms due to fecal
matter being liquid in nature
• Sometimes palpable mass felt
 Left sided lesion :
• Obstructive symptoms because fecal matter is
solid in nature
• Contipation
• Colicky abd pain
• tenesmus
• Rectal bleed
 Rectal lesion
• Per rectal bleeding – at the end of defecation
• Tenesmus
• Pain
• Early morning diarrhea
• Alternating bowel habits
 Focused physical examination
• Weight – loss of weight & appetite
• Look for signs of anaemia – due to blood loss
• Abdominal examination for mass
• Digital rectal examination for rectal Ca –
neoplasm felt as nodular like indurated bases ,
irregular edges , may ulcerate and have
contact bleeding. Fixity of mass can also be
assessed
Screening
 Family History And Risk Factor
• Family history (FH) is a well-established risk factor for
colorectal cancer (CRC). It is affected by first-, second- and
third-degree relatives, and might include positive family
history from both parents.
• Familial Relative Risk (FRR) of developing CRC increases with
greater number of affected FDRs irrespective of second-
degree relatives (SDRs) or third-degree relatives (TDRs).
 Familial Factors – Risks for CRC
Syndrome Distrubution Histology Malignant Other
potential Lesions
Familial Large Intestine Adenoma Common none
Adenomatous
Polyposis
Gardner Large and Adenoma Common Multiple
Syndrome Small Intestine Malignancies
Turcot Large Intestine Adenoma Common BrainTumors
Syndrome
Nonpolyposis Large Intestine Adenoma Common Endometrial
Syndrome and Ovarian
Tumors
Peutz Jeghers Small,Large Hamartoma Rare Multiple
Syndrome Intestine, Malignancies
Stomach
Juvenile Large and Hamartoma Rare Congenital
Polyposis Small Intestine Anomalies
 Other Risk Factors
• Smoking
• Diabetes mellitus
• Obesity
• Alcohol consumption
• Meat consumption
 Genetic Changes in CRC
• GENETIC CHANGES MECHANISM
 Activation of proto- – the mutational activation of
oncogenes (K-ras) an oncogene followed by and
 Loss of tumour- suppressor coupled with the loss of genes
gene activity (APC,DCC) that normally suppress
 Abnormalities in DNA tumorigenesis
repair genes (hMSH2,
hMLH1), especially
HNPCC syndromes
 FOBT
• Faecal test is a non-invasive tool for screening CRC in general population. It
can detect presence of blood, proteins e.g. enzyme M2-PK and DNA. 2
ways – iFOBT, Gfobt
• In a meta-analysis of fair to high quality evidence, the pooled sensitivity to
detect CRC was 74% (95% CI 62 to 83) for quantitative test methods and
79% (95% CI 61 to 90) for qualitative test methods.
 Sigmoidoscopy
• Flexible sigmoidoscopy needs less rigorous bowel
preparation and can be performed as a clinic base
procedure without the need for sedation. Small
polyps can be biopsied during procedure but
excision of larger lesions (>1cm) is usually
performed during subsequent colonoscopy.
• Sigmoidoscopy reduces the CRC incidence by 18-
32% and mortality by 26-38% in general
population. There is low incidence of bowel
perforations associated with it.
 Colonoscopy
• Colonoscopy is the screening modality that has
the ability to visualise the colonic mucosa
directly, perform biopsy and excise polyps. It can
detect proximal lesions that would be missed by
screening sigmoidoscopy and has been shown to
reduce risk of cancer in the right colon.
• Screening colonoscopy reduces overall CRC
incidence significantly by 56% and death by 68%.
For those who has had colonoscopy especially for
screening, the risk of CRC is strongly reduced by
91% up to 10 years.
 CCE
• Colon capsule endoscopy (CCE) is able to obtain
images of the colon by using tiny video cameras
embedded in the two ends of an ingested capsule
that take images as the capsule traverses the colon.
The technique is less invasive but does not allow
biopsy or polyp removal.
 CT colonography
• CT colonography involves in obtaining multiple, thin slice CT data and using
computers to construct images of the bowel mucosa in two or three dimensions
thus enabling polyps to be detected.
• CT colonography requires bowel preparation similar to optical colonoscopy and
during procedure air or carbon dioxide are introduced into the rectum via a rubber
catheter. No sedation is required and patient is usually able to return to work post
procedure.
 CEA
• There is no recommendation made by the US
Preventive Services Task Force, NICE
guidelines and SIGN guidelines on the use of
serum carcinoembryonic antigen (CEA) test for
CRC screening.
 Referrence
• CPG Management of Colorectal Carcinoma
2017