IM 3B: ONCOLOGY

COLORECTAL CANCER RISK FACTORS:

SOURCE: 2017 PPT Diet
- Animal fat
COLORECTAL CANCER - Insulin resistance
Incidence rate has decreased significantly during the past 25 years (attributed to - Fiber
screening) Hereditary syndromes
Mortality rate in the US have decreased by approximately 25% - Polyposis coli
- Resulting largely from earlier detection and improved treatment - MYH assoc polyposis
- Hereditary non polyposis colon cancer
PATHOGENESIS: Inflammatory bowel disease
Most colorectal cancers arise from adenomatous polyps Streptococcus bovis bacteremia
- A polyp is a grossly visible protrusion from the mucosal surface and may be Tobacco use
classified
o Non-neoplastic hamartoma(e.g. juvenile polyp)
o Hyperplastic mucosal proliferation(hyperplastic polyp)
o Adenomatous polyp
Only adenomatous are clearly premalignant, and only a minority of adenomatous
polyps evolve into cancer
Adenomatous polpys may be found in the colons of 30% of middle-aged and -50%
of elderly people: < 1% of polyps ever become malignant
Most polyps produce no symptoms and remain clinically undetected
Occult blood in the stool is found in <5% of patients with polyps

MOLECULAR CHANGES:
- Point mutation in the K-ras protooncogene
- Hypomethylation of DNA-leading to gene activation CLINICAL FEATURES:
- Loss of DNA (allelic loss) at the site of a tumor suppressor gene (the adenomatous
- Symptoms vary with the anatomic location of the tumor
polyposis coli [APC] gene) on the long arm of chromosome 5 (5q21)
- Allelic loss at the site of a tumor-suppressor gene located on chromosome 18q (the
Cancers arising in the cecum and ascending colon
deleted in colorectal cancer [DCC] gene)
- Allelic loss at chromosome 17p associated with mutations in the p53 tumor May become quite large without resulting in any obstructive symptoms or
noticeable alterations in bowel habits
suppressor gene Commonly ulcerate->leading to chronic blood loss->symptoms of anemia
Random fecal occult blood test may be negative
POLYPS Unexplained presence of iron-deficiency anemia in any adult mandates a
Probability of an adenomatous polyp becoming a cancer depends on the gross thorough endoscopic and /or radiographic visualization of the entire large
appearance of the lesion, its histologic features, and its size
bowel
Adenomatous polyps
- Pedunculated (stalked)
- Sessile(flat-based)- develop more frequently to invasive cancers Transverse and descending colon tumors
Stool becomes more formed at this segment
Histologically, adenomatous polyps may be Tend to impede the passage of stool
- Tubular
- Villous mostly sessile, become malignant more than three times as often as Development of abdominal cramping, occasional obstruction, and even
perforation
tubular adenomas
- Tubulovillous Radiographs of the abdomen often reveal characteristic annular, constricting
lesions(apple-core) or (napkin-ring)
2.5 cm in size- 10% are invasive cancers

IM 3B: Oncology- Colorectal cancer , Fame Taclobao 1 of 3

Rectosigmoid tumors
Are often associated with hematochezia, tenesmus and narrowing of the
caliber of stool
Anemia is an infrequent
Development of rectal bleeding and/or altered bowel habits demands a
prompt digital rectal examination and proctosigmoidoscopy

STAGING:

PATTERN OF SPREAD:
Colorectal spread to regional lymph nodes or to the liver via the portal venous
circulation
Liver- most frequent visceral site of metastasis
- The initial site of distant spread in one-third of recurring colorectal cancers
- Involved in more than two-thirds of such patients at the time of death
Colorectal cancer rarely spreads to the lungs, supraclavicular lymph nodes, bone,
or brain without prior spread to the liver
- Major exception to this rule occurs in patients having primary tumors in the distal
rectum, from which tumor cells may spread through the paravertebral venous
plexuses
Historically, median survival after the detection of distant metastases is 6-9 months
to 24-30
- But effective systemic therapy is significantly improving this prognosis

TREATMENT:
Total resection of tumor is the optimal treatment
Evaluation for the presence of metastatic disease should be performed before
surgery
Colonscopy of the entire large bowel- to identify synchronous neoplasms and/or
PROGNOSTIC FACTORS: polyps
Most recurrent after a surgical resection of a large-bowel cancer occur within the The detection of metastases should not preclude surgery in patients with tumor-
first 4 years related symptoms such as bleeding or obstruction
The 5-year survival in patients with colorectal cancers is stage-related - Use of a less radical operative procedure
- Has improved during the past several decades At the time of laparotomy
- Most plausible explanation for this improvement is the more thorough - The entire peritoneal cavity should be examined
intraoperative and pathologic staging - Inspection of the liver,pelvis, and hemidiaphragm and careful palpation of the full
The prognosis following the resection of a colorectal cancer is not related merely to length of the large bowel
the presence or absence of regional lymph node involvement
Prognosis is more precisely gauged by ROLE OF RADIATION THERAPY:
- The number of involved lymph nodes(one to three lymph nodes (N1) four or Radiation therapy to the pelvis- recommended for patients with rectal cancer
more lymph nodes (N2)) - Reduces the 20-25% probability of regional recurrences following complete
- Number of nodes examined surgical resection of stage II or III esp tumors that penetratd the serosa
Minimum of 12 sampled lymph nodes is thought necessary to accurately define - Increased risk of recurrence is believed to be due to the fact that the contained
tumor stage anatomic space within the pelvis limits the extent of the resection
More nodes examined, the better
IM 3B: Oncology- Colorectal cancer , Fame Taclobao 2 of 3
 - Rich lymphatic network of the pelvic side wall facilitates the early spread of FOLFIR and FOLFOX are equal in efficacy in metastatic disease- produce median
malignant cells survivals of 2 years
Total mesorectal excision
- Appears to reduce the disease recurrence to -10% MONOCLONAL ANTIBODIES:
Either pre- or postoperatively reduces the pelvic recurrences but does not appear Monoclonal antibodies are also effective in patients with advances colorectal
to prolong survival cancer
Combining radiation therapy with 5-fluorouracil (5-FU) based chemotherapy Cetuximab and Panitumumab
- Preferably prior to surgical resection lowers local recurrences rates and - Directed against the epidermal growth factor receptor(EGFR)- a transmembrane
improves overall survival glycoprotein involved in signaling pathways affecting growth and proliferation of
- 5-FU acts as a radiosensitizer when delivered together with radiation therapy tumor cells
Radiation therapy is not effective as the primary treatment of colon cancer - When given alone, have been shown to benefit a small proportion of previously
treated patients
SYSTEMIC TREATMENT: - Cetuximab appears to have therapeutic synergy with such chemotherapeutic
5-FU remains the backbone of treatment agents as irinotecan, even in patients previously resistant to this drug
Concomitant administration of folinic acid (leucovorin)improves the efficacy of 5-FU - Suggests that cetuximab can reverse cellular resistance to cytotoxic
in patients with advanced colorectal cancer chemotherapy
- Presumably by enhancing the binding of 5-FU to its targeted enzyme - The anti bodies are not effective in the approximate 40% subset of colon tumors
thymidylate synthase that contain mutated K-ras
5-FU is generally administered intravenously but may also be given orally in the - Can lead to an acne-like rash, with the development and severity of the rash being
form of capecitabine correlated with the likelihood of antitumor efficacy.
The administration of 5-FU and LV for 6 months after resectionof tumor in patients - Bevacizumab is a monoclonal antibody directed against the vascular endothelial
with stage III disease growth facto (VEGF)
- 40% decrease in recurrence rates - Addition to irinotectan containing combinations and to FOLFOX appeared to
- 30% improvement in survival significantly improve the outcome vs chemotherapy alone
The likelihood of recurrences has been further reduced when oxaliplatin has been - Can lead to hypertension,proteinuria , and an increased likelihood of
combined with 5-FU and LV( e.g. FOLFOX) thromboembolic events

ADJUVANT TREATMENT: METASTECTOMY:

Patients with stage II tumors do not appear to benefit from adjuvant therapy Patients with solitary hepatic metastases without clinical or radiographic evidence
Generally restricted to those patients having biological characteristics that place of additional tumor involvement should be considered for partial liver resection
them at higher likelihood for recurrence Associated with 5-year survival rates of 25-30% when performed.
- Perforated tumors
- T4 lesions
- Lymphovascular invasion
Addition of oxaliplatin to adjuvant treatment for patients older than age 70 and
those with stage II disease does not appear to provide any therapeutic benefit
Oxaliplatin a platinum analogue
Improves the response rate when added to 5-FU and LV(FOLFOX) as adjuvant for
resected tumors and initial treatment of patients with metastatic disease
Oxaliplatin frequently causes a dose-dependent sensory neuropathy that often but
not always resolve following the cessation of therapy
Irinotecan (CPT-11) a topoisomerase 1 inhibitor prolongs survival when
compared to supportive care in patients whose diseases has progressed on 5-FU
FOLFIRI( combination with 5-FU and folinic acid) improves response rate and
survival in metastatic disease
Diarrhea is the major side effect from irinotecan

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