Lower GIT Cancers

Dr Alex Mogere
Consultant Physician
• Lower gastrointestinal cancers include malignant tumors of the colon,
rectum, and anus.
• Most colorectal cancers, regardless of aetiology, arise from
adenomatous polyps.
POLYPS
• A polyp is a grossly visible protrusion from the mucosal surface
Classification:
o nonneoplastic hamartoma (e.g., juvenile polyp),
o hyperplastic mucosal proliferation (hyperplastic polyp),
o adenomatous polyp.
• 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 and ∼50% of elderly people; however, <1% of polyps ever become
malignant
Cont. Polyps
• Occult blood in the stool is found in <5% of patients with polyps.

Pathogenesis:
• developmental steps toward carcinogenesis include point mutations in
the K-ras protooncogene; hypomethylation of DNA, leading to gene
activation; loss of DNA at the site of a tumor-suppressor gene
• cancer is believed to develop only in those polyps in which most (if not
all) of these mutational events take place.
• the probability of an adenomatous polyp becoming a cancer depends on
the gross appearance of the lesion, its histologic features, and its size
Cont. Polyps
• Adenomatous polyps may be pedunculated (stalked) or sessile (flat-
based).
• Invasive cancers develop more frequently in sessile polyps.
• Histologically, adenomatous polyps may be tubular, villous (i.e.,
papillary), or tubulovillous.
• Villous adenomas, most of which are sessile, become malignant >
than x3 as often as tubular adenomas.
• On detection of an adenomatous polyp, the entire large bowel should
be visualized endoscopically
Cont. Polyps
• Colonoscopy should be repeated periodically:30–50% probability of
developing another adenoma and are at a higher-than-average risk
for developing a colorectal Ca.
• Adenomatous polyps are thought to require >5 years of growth
before becoming clinically significant
• Colonoscopy need not be carried out more frequently than every 3
years for the vast majority of patients.
Risk factors for the Devt of Colorectal Ca
Cont. aetiology/risk factors
• Mortality from colorectal Ca is directly correlated with per capita
consumption of calories, meat protein, and dietary fat and oil as well
as elevations in the serum cholesterol conc. and mortality from CAD.
• Up to 25% of patients with colorectal Ca have a Fhx of the disease,
Hereditable (AutosomaL Dominant) gastrointestinaL polyposis syndromes
Distribution of colorectal Ca
Classification(duke’s)
• Duke A: the tumor penetrates into the mucosa of bowel wall no further
• Duke B: B1: tumor penetrates into but not through the muscular layer
B2: tumor penetrates through muscular lyr
• Duke C: C1: tumor penetrates into but not through the muscular layer
,there is pathogenic evidence of colon Ca in the LNs
C2: tumor penetrates through the muscukar lyr with
pathological evidence Ca in the LNs
• Modified Duke D: the tumor has spread beyond, there’s mets
TNM Staging
Node(N), Metastasis(M)
Stages
Prognosis
• related to the depth of tumor penetration into the bowel wall and the
presence of both regional lymph node involvement and distant
metastases
• Most recurrences after a surgical resection of a large-bowel cancer
occur within the first 4 years,
Staging and prognosis colorectal Ca
Predictors of poor outcome following total
surgical resection of Colorectal Cancer
Clinical presentation
• Symptoms vary with the anatomic location of the tumor
• Because stool is relatively liquid as it passes through the ileocecal
valve into the Rt. colon, Cas arising in the cecum and ascending colon
may become quite large without resulting in any obstructive
symptoms or noticeable alterations in bowel habits
Clinical presentation
Right sided
• Abdominal pain
• Bleeding
• Weakness/fatigue
• Palpable abdominal mass
• Malaena
• +/- bowel obstruction
• Palpiations
• +/- angina
Left sided
• Colicky abd pain
• +/- perforation
• Bleeding
• Obstruction
• Weakness/fatigue
• Ribbon like stools
• Nausea and vomiting
• “Apple-core’’ or napkin
ring(radiography)
Clinical presentation: rectum
• Pain
• Rectal bleeding
• Bloody stools
• Altered bowel habits
• Perineal buttock pain
Clinical presentation: rectosigmoid
• Hematochezia
• Tenesmus
• Narrowed caliber of stool
• Anemia is infrequent
Primary prevention
• Aspirin and other NSAIDs, which are thought to suppress cell
proliferation by inhibiting prostaglandin synthesis
• This effect of ASA on colon carcinogenesis increases with the
duration and dosage of drug use.
• Oral folic acid supplements and oral Ca supplements appear to
reduce the risk of adenomatous polyps and colorectal Cas in case-
controlled studies.
• vitamin D as a form of chemoprevention is under study
• Antioxidant vitamins such as ascorbic acid, tocopherols, and β-
carotene are ineffective
Cont. primary prevention
• Estrogen replacement Tx has been associated with a red in the risk of
colorectal Ca in women, due to effect on bile acid synthesis and
composition or by decreasing synthesis of IGF-I.
Screening
The rationale for colorectal Ca screening programs:
o the removal of adenomatous polyps will prevent colorectal Ca,
o earlier detection of localized, superficial Cas in asymptomatic
individuals will increase the surgical cure rate
• Such screening programs are particularly important for individuals
with a family history of the disease in first-degree relatives.
• Many programs directed at the early detection of colorectal Cas have
focused on digital DREs and fecal occult blood (i.e., stool guaiac)
testing
Cont. Screening
• DRE should be part of any routine P/E in adults >40 years, serving as a
screening test for prostate Ca in men, a component of the pelvic exam
in women, and an inexpensive maneuver for the detection of masses
in the rectum.
• But due to proximal migration of colorectal tumors, its(DRE) value as
an overall screening modality for colorectal Ca has become ltd
• Stool occult test:About 50% of Pts with documented colorectal Cas
have a neg fecal occult blood test(FOBt), consistent with the
intermittent bleeding pattern of these tumors
Cont. screening
• A colorectal neoplasm will not be found in most asymptomatic
individuals with occult blood in their stool
• Pts with FOBt +ve routinely undergo further evaluation, including
sigmoidoscopy and/or colonoscopy—procedures that are not only
uncomfortable and expensive but also associated with a small risk for
significant complications
Cont. screening
• Prospectively controlled trials have shown a statistically significant
reduction in mortality rate from colorectal Ca for individuals
undergoing annual stool guaiac screening.
• this benefit only emerged after >13 years of follow-up and was
extremely expensive to achieve, because all positive tests (most of
which were falsely positive) were followed by colonoscopy.
• The introduction of computed tomography (CT) scanning led to the
development of virtual (i.e., CT) colonography as an alternative to the
growing use of endoscopic screening techniques
Cont. Screening
• ACS and the NCCN (American) suggest either FOBt annually coupled
with flexible sigmoidoscopy every 5 years or colonoscopy every 10
years beginning at age 50 in asymptomatic individuals with no
personal or family history of polyps or colorectal Ca.
• flexible sigmoidoscopy requires only an enema as preparation and can
be accurately performed by nonspecialty physicians or physician
extenders
• Colonoscopy is superior to double-contract barium enema and also
has a higher sensitivity for detecting villous or dysplastic adenomas or
Cas than the strategy using FOBt and flexible sigmoidoscopy.
Summary strategies for colorectal Ca screening
MX
• Medical and surgical Mx
• Medical Mx: chemotx, targeted tx/biologics, radiotx
MX
• Total resection of tumor is the optimal treatment when a malignant
lesion is detected in the large bowel
• Thorough physical P/E, LFT, CEA, and a CT scan of the chest, abdomen,
and pelvis, should be performed before surgery
• When possible, a colonoscopy of the entire large bowel should be
performed to identify synchronous neoplasms and/or polyps.
• The necessity for a primary tumor resection in asymptomatic
individuals with metastatic disease is controversial
Cont. Mx
• At the time of laparotomy, the entire peritoneal cavity should be examined,
with thorough inspection of the liver, pelvis, and hemidiaphragm and careful
palpation of the full length of the large bowel
• Radiation Tx to the pelvis is recommended for pts with rectal Ca because it
reduces the 20–25% probability of regional recurrences following complete
surgical resection of stage II or III tumors, especially if they have penetrated
through the serosa.
• Combining radiation Tx with 5-FU-based chemotx, preferably prior to surgical
resection, lowers local recurrence rates and improves overall survival.
• Preoperative radioTx is indicated for pts with large, potentially unresectable
rectal Cas
Surgical Mx
Colostomy
Systemic Tx: chemotx
• 5-FU remains the backbone of treatment for this disease
• Partial responses are obtained in 15–20% of patients.
• The concomitant administration of folinic acid (leucovorin) improves
the efficacy of 5-FU in patients with advanced colorectal cancer,
• 5-FU is generally administered IV but may also be given P.O in the
form of capecitabine (Xeloda) with seemingly similar efficacy
• Irinotecan (CPT-11), a topoisomerase 1 inhibitor, prolongs survival
when compared to supportive care in pts whose disease has
progressed on 5-FU
Systemic Tx: chemotx
• The add. of irinotecan to 5-FU and leucovorin (e.g., FOLFIRI) improves
response rates and survival of pts with mets.
• Oxaliplatin, a platinum analogue, also improves the response rate
when added to 5-FU and LV (FOLFOX) as initial treatment of patients
with metastatic disease
FOLFIRI regimen
• Irinotecan, 180 mg/m2 as a 90-min infusion on day 1;
• LV, 400 mg/m2 as a 2-h infusion during irinotecan administration;
• immediately followed by 5-FU bolus, 400 mg/m2, and 46-hr cont.
infusion of 2.4–3 g/m2 every 2 weeks

Irinotecan mjr s/e: diarrhoea

FOLFOX Regimen
• 2-h infusion of LV (400 mg/m2 per day)
• Followed by a 5-FU bolus (400 mg/m2 per day) and 22-hr infusion
(1200 mg/m2) every 2 weeks,
• Together with oxaliplatin, 85 mg/m2 as a 2-h infusion on day 1

Oxaliplatin mjr s/e: dose-dependent sensory neuropathy

Other tx options
• Monoclonal abs are also effective in pts with advanced colorectal ca
• Cetuximab (Erbitux) and panitumumab(Vectibix) are directed against
the epidermal growth factor receptor(EGFR)
• The abs are not effective in the approximate 40% subset of colon
tumors that contain mutated K-ras.
• Pts with solitary hepatic mets without clinical/radiographic evidence
of additional tumor involvement should be considered for partial liver
resection: associated with 5-year survival rates of 25–30% when
performed on selected individuals by experienced surgeons.
Other Tx options
• The administration of 5-FU and LV for 6 months after resection of
tumor in pts with stage III disease leads to a 40% decrease in
recurrence rates and 30% improvement in survival.
• The 5-FU acts as a radiosensitizer when delivered together with
radiation therapy
Post op follow up
• Following recovery from a complete resection, patients should be
observed carefully for 5 years by semiannual physical examinations
and blood chemistry measurements
• If a complete colonoscopy was not performed preoperatively, it
should be carried out within the first several postoperative months.
• Some authorities favor measuring plasma CEA levels at 3-month
intervals because of the sensitivity of this test as a marker for
otherwise undetectable tumor recurrence
Anal Cancer
• Anal cancer: The devt. of anal Ca is associated with HPV infection
• Tx :combining external beam radiation Tx with concomitant chemotx
(5-FU and mitomycin C) has resulted in biopsy proven disappearance
of all tumor in >80% of pts whose initial lesion was <3 cm in size.
• Surgery should be reserved for the minority of individuals who are
found to have residual tumor after being managed initially with
radiation Tx combined with chemotx.
THANK YOU!