18 Colon Cancer Flashcards
1
Q
Epidemiology (p.4)
- New Cases
- mortality rates
A
-
New Cases
- 3rd most common cancer in both men and women.
- incidence rates for colorectal cancer have decreased.
- attributed to the use of colorectal cancer screening tests that detect and remove colorectal polyps before they have progressed to frank malignancy
- among adults 50 years of age and older (among whom screening is recommended.
-
mortality rates
- mortality rates for colorectal cancer have declined in both men and women
- These declines reflect declining incidence as well as improvements in early detection and treatment.
2
Q
Risk Factors (p.5-8+15-18+30-31)
- Modifiable risk factors
- Non-modifiable risk factors
- Factors that may reduce the risk of colorectal cancer
A
-
Modifiable risk factors
- obesity, physical inactivity, a diet high in red or processed meat, alcohol consumption long-term smoking, and very low intake of fruits and vegetables.
-
Non-modifiable risk factors
- increasing age
- personal or family history of colorectal cancer or polyps
- Family history of colorectal cancer is especially important
- personal history of inflammatory bowel disease (ulcerative colitis and Crohn’s disease), inherited genetic disorders such as familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer [Lynch syndrome], and type 2 diabetes.
- Infection with Helicobacter pylori, Fusobacterium species, and other infectious agents
-
Factors that may reduce the risk of colorectal cancer
- higher blood levels of vitamin D and consumption of milk and calcium.
- Physical activity
- diets rich in fruit, vegetables, cereal fiber and whole grains, dairy products, or fish
- statin therapy
- Regular use of nonsteroidal anti-inflammatory drugs reduces risk but is not recommended for patients at average risk for colorectal cancer because of potential side effects.
- Menopausal hormone therapy may reduce the risk of colorectal cancer but is not recommended for this purpose because of its increase risk of breast cancer, stroke, heart attack, and thromboembolism.
3
Q
Molecular Biology of Colon Cancer (p.19-28+35)
- Grossly colorectal cancers develop/
- These gross changes are accompanied by/
- Most (about 85%) colorectal cancers
- develop/
- characterized by/
- The majority of colorectal cancers begin with mutations of/
- These mutations are associated with development of/
- Activating mutations of the KRAS oncogene/
- seen with development of frank cancers
A
-
Grossly colorectal cancers develop with progression from normal epithelium to adenomatous polyps to polyps with severe dysplasia and finally to invasive cancer
- These gross changes are accompanied by molecular changes that continue to be further elucidated.
-
Most (about 85%) colorectal cancers
- develop along the adenoma-carcinoma sequence
- characterized by chromosomal abnormalities.
-
The majority of colorectal cancers begin with mutations of adenomatous polyposis coli (APC) gene that promotes degradation β-catenin.
- These mutations are associated with development of adenomas, and as many as 90% of patients with colorectal cancer have APC mutations.
-
Activating mutations of the KRAS oncogene are an early event in the adenoma-carcinoma sequence associated with larger adenomas and early cancers.
- KRAS mutations are found in approximately 30% of colorectal cancers, and may be associated with poorer response to epidermal growth factor receptor (EGFR) inhibitors (illustrating the potential for “personalized” colon cancer therapy).
- Inactivating mutations of the tumor suppressor gene TP53, as well as loss of chromosome 18q and SMAD4 are seen with development of frank cancers.
4
Q
Molecular Biology of Colon Cancer (9-14)
- chromosomal instability
- chromosomal unstable colon cancers
- prognosis
- chromosomal stable colon cancers
- characterized by/
- Such tumors have instability in at least/
- Microsatellite instability/
- the initial abnormality/
- CpG island methylator phenotype/
- prognosis
- Familial non-polyposis hereditary colon cancers (Lynch syndrome) show signs/
- familial adenomatous polyposis cancers show/
A
- chromosomal instability is changes in the number of chromosomes or profound structural major chromosomal in tumor cells.
-
Chromosomal unstable colon cancers
- have a poorer prognosis (higher hazard ratio for death) than chromosomal stable colon cancers.
-
chromosomal stable colon cancers
- About 15% of colorectal cancers are chromosomal stable but are characterized by a deficiency of the mismatch repair system exhibited as microsatellite instability.
- Such tumors have instability in at least two of five standard microsatellite markers.
- Microsatellite instability is usually not found in adenomas,
-
the initial abnormality in this sequence may be in Wnt signaling rather than an APC mutation.
- Mutations in BRAF rather than KRAS often occur,
- CpG island methylator phenotype defined as methylation to three or more specific loci is frequently present.
- associated with a more favorable prognosis.
- Familial non-polyposis hereditary colon cancers (Lynch syndrome) show signs of mismatch repair deficiencies and hence microsatellite instability,
- familial adenomatous polyposis cancers show the typical adenoma-carcinoma sequence and associated genetic changes.
5
Q
Pathologic Staging
- Colon and rectal cancers
- originate from/
- grow/
- Cancer cells may spread/
- Pathologic staging,
- determined by/
- vs. clinical staging
- Estimates of prognosis (cure rates) require/
A
-
Colon and rectal cancers
- originate from the mucosa of the intestine
- grow radially and longitudinally.
- Cancer cells may spread to regional lymph nodes or to distant sites within the abdomen or elsewhere.
-
Pathologic staging,
- determined by both pathologic analysis of resected tissues (i.e. resected segment of colon together with resected regional lymph nodes) and either pathologic confirmation or clinical suspicion (radiographic evidence) of metastatic disease,
- more precise than clinical staging based upon physical findings, signs and symptoms, and imaging studies.
-
Estimates of prognosis (cure rates) require
- accurate staging.
- decisions (e.g. recommendations regarding post-resection chemotherapy)
- development of new stage-specific treatments.
6
Q
Pathologic Staging (p.36)
- The earliest stage cancers are confined to/
- invasive cancer/
- The different T designations refer to/
- T1
- T2
- T3
- T4
- the staging systems do not incorporate/
A
-
The earliest stage cancers are confined to the mucosa of the colon.
- the cancer does not have potential for spread and is often referred to as carcinoma in situ.
- Once the cancer invades into the submucosa of the intestinal wall, it is an invasive cancer with the potential to spread to regional lymph nodes and distant sites.
-
The different T designations refer to the depth of radial penetration into or through the intestinal wall:
- T1 = invasion into the submucosa;
- T2 = invasion into the muscularis propria;
- T3 = invasion into the subserosa or beyond without involvement of other organs;
- T4 = invasion into adjacent organs or perforation of the visceral peritoneum.
- Although the extent of longitudinal spread is relevant to surgery, as margins that are free of cancer cells are sought both proximally and distally, note that the staging systems do not incorporate the length or actual size of the cancer.
7
Q
Pathologic Staging (p.37)
- The N stage
- N0
- N1
- N2
- Accurate staging requires/
- M stage
- M1
- MX vs. M0
- hierarchy of staging
A
-
The N stage, or nodal stage, ranges from
- N0 (none of the resected lymph nodes contain any cancer cells,
- N1 (1-3 positive nodes)
- N2 (4 or more positive nodes).
-
Accurate staging requires that a sufficient number of lymph nodes be removed at the time of surgery for resection an individual’s colon cancer.
- removal of fewer than 12 lymph nodes is an independent negative prognostic factor in patients with colon cancer.
-
M stage
- if metastatic disease is confirmed the M stage is M1.
- If metastatic disease is not confirmed to be present, more commonly a designation of MX is given as the patient’s entire body has not been pathologically evaluated and found to be free of metastases (M0).
-
hierarchy of staging is M > N > T.
- if metastases are present the patient is stage IV regardless of the T or N stage.
- if the patient is MX but has positive lymph nodes (N1 or N2), the patient is stage III regardless of the T stage.
8
Q
Clinical Presentation (p.38)
- asymptomatic
- the cancer is identified during/
- systemic signs and symptoms
- such as/
- Specific signs and symptoms may be caused by/
A
-
asymptomatic
- the cancer is identified during routine screening or evaluation for unrelated symptoms
- e.g., the patient undergoes a computed tomography (CT) scan for evaluation of hematuria and a colon mass is unexpectedly found on the CT scan
-
systemic signs and symptoms
-
such as weight loss, fatigue, anorexia, and abdominal pain particularly if the cancer is advanced.
- Specific signs and symptoms may be caused by metastatic disease. Extensive liver metastases, for example, may cause jaundice by virtue of either obstruction of the bile duct or extensive replacement of the liver by cancer.
-
such as weight loss, fatigue, anorexia, and abdominal pain particularly if the cancer is advanced.
9
Q
Clinical Presentation:
Other patients may present with signs and symptoms arising from the primary tumor itself (p.42-44)
- If sufficiently large the cancer may cause/
- The friable surface of the cancer will frequently/
- Tumors that penetrate through the wall of the colon may/
- Extension into the parietal peritoneum may result in/
- Growth into the bladder may result in/
A
- If sufficiently large the cancer may cause obstructive symptoms.
- The friable surface of the cancer will frequently shed blood into the GI tract, resulting in anemia and its associated symptoms, stool positive for occult blood, or hematochezia.
- Tumors that penetrate through the wall of the colon may grow into adjoining structures (T4 cancers).
- Extension into the parietal peritoneum may result in localized pain.
-
Growth into the bladder may result in a fistula causing recurrent urinary tract infections and passage of feces (fecaluria) or air (pneumaturia) in the urine.
- Fistulization through the abdominal wall results in a colocutaneous fistula from which feces drain,
- fistulization into other parts of the digestive system may result in fluid and electrolyte abnormalities or nutritional deficiencies due to segments of the intestine being bypassed.
10
Q
Diagnosis (p.46-49+52)
- colonoscopy
- Some abnormalities found
- treatment
- biopsied
- The mucosa of the colon may be incompletely examined if/
- what may also prevent complete examination of the colon
- Air contrast barium enema
- CT evaluation
- either of these examinations can be considered if/
A
- Colorectal cancers are best diagnosed by colonoscopy performed after satisfactory cleansing of the colon and rectum.
- Some abnormalities found on colonoscopy such as polyps may be possible to completely remove,
- in some instances this treatment may be sufficient even for malignant growths
- Other abnormalities can be biopsied for histologic diagnosis.
- The mucosa of the colon may be incompletely examined if pre-procedural cleansing has not been thorough.
- Tortuosity, redundancy, or severe angulations of the colon may also prevent complete examination of the colon.
-
Air contrast barium enema may fail to identify smaller cancers and other mucosal abnormalities.
- tissue is not obtainable for histologic diagnosis.
-
CT evaluation of the colon (“virtual colonoscopy”)
- may be more sensitive than barium enema for identifying small lesions.
- Radiation exposure and cost are greater than for barium enema,
- tissue sampling is not possible.
- either of these examinations can be considered if complete colonoscopic examination of the colon is not possible.
11
Q
Diagnosis:
Once a colorectal cancer has been diagnosed, further studies should be completed as part of the staging workup (p.51-56+58-59)
- A CT scan
- A fused PET/CT scan
- A baseline carcinoembryonic antigen (CEA)
A
-
A CT scan of the chest, abdomen, and pelvis should be obtained to evaluate for locally advanced or distant metastatic disease.
- Due to differing patterns of venous drainage, liver metastases are more apt to be found with colon cancer (hematogenous spread from the colon to the liver via the portal vein),
- lung metastases are more common with rectal cancers (due to venous drainage through the systemic circulation).
- A fused PET/CT scan may help to determine if CT findings are more or less apt to be malignant.
-
A baseline carcinoembryonic antigen (CEA) level should also be measured.
- This can be monitored in the future for increases that may indicate recurrence of disease.
- Elevated CEA has also been shown to have prognostic significance independent of TNM staging,
12
Q
Treatment (p.60)
- If there is no evidence of distant spread on staging studies/
- In some instances the cancer arises in a polyp/
- For this approach, the cancer should be/
A
- If there is no evidence of distant spread on staging studies, complete removal of the cancer with curative intent is usually the initial treatment.
-
In some instances the cancer arises in a polyp, and complete endoscopic removal of the polyp is sufficient treatment of the cancer.
- For this approach, the cancer should be well-differentiated, pedunculated (on a stalk, as this facilitates complete removal) with negative margins of resection, and no angiolymphatic invasion.
13
Q
Treatment (p.61-63)
- the vast majority of colon cancers require/
- The goal for surgical resection/
- To achieve these goals the segment bearing the cancer is removed with/
- With a right (ascending) colon cancer/
- The extent of the intestinal resection is determined by/
- At the conclusion of the operation/
A
-
the vast majority of colon cancers require formal surgical resection.
- may be performed as an open procedure or by minimally invasive (laparoscopic or robotic) means.
- minimally invasive resection of colon cancer has been reported to be oncologically superior to open resection
-
The goal for surgical resection
- to achieve negative margins of resection (both longitudinal and radial margins)
- to remove regional lymph nodes.
- To achieve these goals the segment bearing the cancer is removed with en bloc high ligation and resection of its vascular supply along which are found the relevant regional lymph nodes.
- With a right (ascending) colon cancer, the ileocolic, right colic, and middle colic (or right branch of the middle colic) arteries are ligated and divided.
- The extent of the intestinal resection is determined by the need to achieve negative margins of resection and the portion of intestine supplied by the blood vessels that are ligated.
- At the conclusion of the operation, all known disease should be removed, and the resection specimen should contain sufficient lymph nodes for accurate pathologic staging.
14
Q
Treatment
- Rectal cancers are treated by/
- This technique reduces the risk of/
- Local recurrences after resection of rectal cancer/
- preoperative (also known as neoadjuvant) therapy is rarely given in patients with/
- preoperative chemotherapy and radiation therapy are frequently given to patients with/
- If preoperative staging demonstrates findings of metastatic disease, the extent of metastatic disease and the severity of symptoms caused by the cancer determine/
- if there are widespread metastases and no symptoms caused by the colon cancer itself, then resection of the colon cancer may perhaps /
- if there are widespread metastases but also complete obstruction caused by the colon cancer primary tumor, then surgical treatment of the colon cancer primary (either resection or creation of a proximal stoma) /
A
-
Rectal cancers are treated by resection of the rectum together with en bloc total resection of its mesentery in which are found lymph nodes, fat, and blood vessels.
- This technique reduces the risk of positive radial margins of resection that lead to local recurrences after surgery.
- Local recurrences after resection of rectal cancer, in contrast to colon cancer, is not uncommon and is very problematic, as local recurrences frequently involve the bony structures or pelvic organs and may not be curable.
- preoperative (also known as neoadjuvant) therapy is rarely given in patients with non-metastatic colon cancer,
- preoperative chemotherapy and radiation therapy are frequently given to patients with intermediate stage rectal cancer in order to decrease the incidence of local recurrence after surgery.
-
If preoperative staging demonstrates findings of metastatic disease, the extent of metastatic disease and the severity of symptoms caused by the cancer determine if and when surgery for resection of the colon cancer is performed.
-
if there are widespread metastases and no symptoms caused by the colon cancer itself, then resection of the colon cancer may perhaps never be performed as it does not relieve symptoms nor does it improve survival.
- Instead, systemic treatment usually in the form of chemotherapy will be given.
- if there are widespread metastases but also complete obstruction caused by the colon cancer primary tumor, then surgical treatment of the colon cancer primary (either resection or creation of a proximal stoma) may be necessary before systemic treatment of the metastatic can begin.
-
if there are widespread metastases and no symptoms caused by the colon cancer itself, then resection of the colon cancer may perhaps never be performed as it does not relieve symptoms nor does it improve survival.
15
Q
Treatment (p.64-69)
- metastatic disease
- usually/
- if limited and especially if localized to the liver or lungs, /
- Treatment of metastatic disease unsuitable for resection or ablation consists of/
- A frequently used regimen
- systemic therapy (chemotherapy) after surgery that removed all known disease (adjuvant therapy)
- recommended for/
- Most regimens
- the FOLFOX4/
- considered/
- Other regimens include/
A
-
metastatic disease
- usually incurable
-
if limited and especially if localized to the liver or lungs,
- may be possible to resect or ablate for cure in some patients
- an initial course of systemic (usually chemo-) therapy is usually given during which the patient is closely followed for development of additional sites of a disease that might preclude attempts at resection or ablation of the metastatic disease.
-
Treatment of metastatic disease unsuitable for resection or ablation consists of systemic therapy.
- A frequently used regimen is FOLFOX4 plus bevacizumab, a recombinant human monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A).
- In selected patients, systemic therapy (chemotherapy) after surgery that removed all known disease (adjuvant therapy) may be beneficial.
- recommended for individuals with stage III (positive lymph nodes).
- Most regimens are fluorouracil (5-FU) based.
- the FOLFOX4 consisting of oxaliplatin, leucovorin, and fluorouracil (5-FU) resulted in 72.9% overall survival at 6 years in stage III patients.
- considered standard treatment
- Other regimens include capecitabine plus oxaliplatin, and capecitabine alone.
