110 : Lower GI Cancers Flashcards
Polyp is a grossly visible protrusion from the mucosal surface. 3 types of polyps are:
- Nonneoplastic hamartoma (e.g. juvenile polyp)
- Hyperplastic mucosal proliferation (hyperplastic polyp)
- Adenomatous polyp
Which type of polyp is premalignant?
Adenomas
Adenomatous polyps are seen in 30% of middle-aged and 50% of elderly people. What percentage of polyps become malignant?
<1%
Developmental steps toward carcinogenesis in colorectal cancer
- Point mutations in K-ras protooncogene
- Hypomethylation of DNA –> gene activation
- Loss of DNA (allelic loss) at the site of a tumor-suppressor gene (APC geneL on 5q21
- Allelic loss at the site of a tumor-suppressor gene on chromosome 18q (the deleted in colorectal cancer [DCC] gene)
- Allelic loss at chromosome 17p, associated with mutation in p53 tumor-suppressor gene
Probability of an adenomatous polyp to become a cancer depends on
- Gross appearance of lesion (pedunculated or sessile)
- Histologic features (tubular, villous, tubulovillous)
- Size (<1.5cm is negligible, 1.5-2.5cm as intermediate, >2.5cm as substantial)
Characteristics of polyp that can become malignant
Sessile polyps
Villous adenomas
>2.5cm in size
When should colonoscopy be done in patients with adenomatous polyp in the absence of documented malignancy?
Colonoscopy should be done periodically at least every 3 years
Risk factors for the development of colorectal cancer
- Diet: Animal fat
- Hereditary syndromes : Polyposis coli, MYH-associated polyposis, Hereditary nonpolyposis colon cancer [HNPCC] (or Lynch’s syndrome)
- Inflammatory bowel disease
- Streptococcus bovis bacteremia (endocarditis, septicemia)
- ?Tobacco use
T or F: Colorectal cancer occurs more often among upper socioeconomic population who live in urban areas.
True
Growth factor implicated to stimulate proliferation of intestinal mucosa, common among obese persons, and associated with colorectal cancers
Insulin-like growth factor type I (IGF-I)
T or F: Accdg to studies and trials, dietary fiber and diets high in fruits and vegetables failed to show that it can prevent colorectal cancer and recurrence of colorectal adenomas
True
Rare condition characterized by the appearance of thousands of adenomatous polyps throughout the large bowel transmitted via autosomal dominant trait
Polyposis coli (familial polyposis of the colon)
Molecular pathology in polyposis coli
- Deletion in long arm of chromosome 5 (including APC gene) causing allelic loss
- Absence of tumor-suppressor genes that would normally inhibit neoplastic growth
Subset of polyposis coli presenting with soft tissue and bony tumors, congenital hypertrophy of retinal pigment epithelium, mesenteric desmoid tumors, and ampullary cancers
Gardner’s syndrome
Polyposis coli with appearance of malignant tumors of the central nervous system
Turcot’s syndrome
Prognosis for polyposis coli if not treated surgically
Colonic polyps appear by age 25
Colorectal cancer will develop in almost all patients before age 40
Surgical treatment and prevention for polyposis coli
Total colectomy
Medical therapy for polyposis coli that can decrease the number and size of polyps temporarily
- NSAIDS such as Sulindac
2. Selective COX-2 inhibitors such as Celecoxib
Risk of an offspring to develop polyposis coli
50% risk
Screening by annual flexible sigmoidoscopy until age 35 or proctosigmoidoscopy
Location of polyps in polyposis coli
Cecum to anus
Definitive diagnosis for polyposis coli
Detection of APC gene mutation from DNA testing
Rare autosomal recessive syndrome caused by biallelic mutation in the MUT4H gene
MYH-associated polyposis (MAP)
Recommended surveillance for patients with MYH-Associated Polyposis
Annual to biennial colonoscopic surveillance starting at age 25-30
An autosomal dominant trait, also called the Lynch’s syndrome, associated with high frequency of colorectal cancer arising in proximal large bowel, with median age of <50 years
Hereditary nonpolyposis colon cancer (HNPCC)
Characteristics of HNPCC
- Three or more relatives with histologically documented colorectal cancer, one of whom is a first-degree relative of the other two
- One or more cases of colorectal cancer diagnosed before age 50 in the family
- Colorectal cancer involving at least two generations
HNPCC is associated with multiple primary cancers. Other associated cancers aside from colorectal cancer include
- Ovarian CA
- Endometrial CA
- Gastric, small-bowel, genitourinary, pancreaticobiliary and sebacious skin tumors
In HPNCC, recommended screening for family members would be
Annual or biennial colonoscopy beginning at age 25
WITH intermittent pelvic ultrasonography AND endometrial biopsy for afflicted women
Germline mutation of these genes are associated with HNPCC
hMSH2 on chromosome 2
hMLH1 on chromosome 3
Which inflammatory bowel disease is more associated with colorectal cancer, ulcerative colitis or Crohn’s disease?
Ulcerative colitis
In a patient with IBD of more than 15 years who continue to experience exacerbations, what can you recommend to reduce the risk of cancer?
Surgical removal of colon
Most effective class of chemopreventive agents thought to suppress cell proliferation by inhibiting prostaglandin synthesis as primary prevention for colorectal cancer
Aspirin
and other NSAIDs
Other drugs that appear to reduce the risk of colorectal cancer
- Oral folic acid supplements
- Oral calcium supplements
- Estrogen replacement therapy (decreases IGF-I)
Suggested screening for colorectal cancer by American Cancer Society and NCCN
- Fecal occult blood testing ANNUALLY + Flexible sigmoidoscopy EVERY 5 years
OR - Colonoscopy EVERY 10 years
Starting at age 50 in ASYMPTOMATIC pt with NO personal or family history of polyps or colorectal cancer
Presenting symptoms of lesions on the ascending colon
- Cancers can become quite large without resulting in any obstructive symptoms or alteration in bowel habits since the stool passing here is liquid
- Associated symptoms : Fatigue, palpitation, angina pectoris
- Hypochromic, microcytic anemia (IDA)
- Tumors may bleed intermittently
Presenting symptoms of lesions in the transverse and descending colon
- Abdominal cramping, occasional obstruction, and perforation
- Radiographs: Annular constricting lesions (“apple-core” or “napkin-ring”)
Presenting symptoms of lesions in the rectosigmoid
- Hematochezia, tenesmus, narrowing of caliber of stool
2. Anemia is infrequent
Basis of prognosis for colorectal cancer
- DEPTH of tumor penetration into bowel wall
- presence of REGIONAL LYMPH NODE involvement
- distant METASTASES
Stage of colorectal cancer wherein tumors penetrate through the muscularis but have not spread to lymph nodes
Stage II (T3-4N0M0)
Stage of colorectal cancer showing a regional lymph node involvement
Stage III (TXN1-2M0)
Minimum number of lymph nodes to be examined to define tumor stage in colorectal cancer
at least 12 LN
Most frequent visceral site of metastasis
Liver
T or F: In general, colorectal cancer rarely spreads to the lungs, supraclavicular lymph nodes, bone, or brain without prior spread to the liver
True
Except primary tumors in distal rectum which spreads through the paravertebral venous plexus escaping portal venous system and reaching lungs or supraclavicular LN
T or F: Plasma CEA level obtained preoperatively, predicts eventual tumor recurrence
True
CEA titer >5 ng/mL
Optimal treatment in colorectal cancer when malignant lesion is detected in the large bowel
Total resection of tumor
What evaluation procedures to detect metastatic disease should be done in pt with colorectal cancer prior to surgery?
- Thorough physical exam
- Biochemical assessment of liver function
- Measure plasma CEA level
- CT scan of chest, abdomen and pelvis
When possible, colonoscopy of entire large bowel to detect synchronous neoplasma and/or polyps
Follow-up of patients with colorectal cancer after complete resection and recovery
- Semiannual physical examinations and blood chemistry measurements for 5 years
- Complete colonoscopy post op, if not yet done
- CEA levels at 3-month intervals
- Endoscopic surveillance at triennial intervals
- Some recommended CT scan of abdomen annually for first 3 post-operative years
Recommended for patients with rectal cancer to reduce the probablity of regional recurrences following surgical resection of stage II or III tumors, especially if serosa is penetrated
Radiation therapy to the pelvis (either pre-op or post-op)
But does not prolong survival
In rectal cancer, combining radiotherapy with this chemotherapy using this drug prior to surgery, lowers local recurrence rates and improve survival
5-fluorouracil (5-FU)-based chemotherapy
Backbone of treatment for colorectal cancer
5-FU
In patients with advanced colorectal cancer, administration of this medication improves efficacy of 5-FU by enhancing its binding to its target enzyme, thymidylate synthase
Folinic acid (Leucovorin)
5-FU can be given orally in the form of this drug with seemingly similar efficacy
Capecitabine (Xeloda)
Adding this topoisomerase 1 inhibitor to 5-FU and Leucovorin improves response rates and survival of patients with metastatic colorectal disease
Irinotecan
FOLFIRI regimen
FOLFIRI regimen
- Irinotecan 180mg/m2 as a 90-min infusion on day 1
- Leucovorin 400mg/m2 as 2-h infusion during irinotecan administration
- Immediately followed by 5-FU bolus, 400mg/m2 and 46-h continuous infusion of 2.4-3g/m2 every 2 weeks
Major side effect of Irinotecan
Diarrhea
A platinum analogue added to 5-FU and Leucovorin that improves response rate as initial treatment of patients with metastatic disease
Oxaliplatin
FOLFOX regimen
FOLFOX regimen
- Leucovorin (400mg/m2 per day) as 2-h infusion
- Followed by 5-FU bolus (400mg/m2 per day) and 22-h infusion (1200mg/m2) every 2 weeks
- Together with Oxaliplatin 85mg/m2 as a 2-h infusion on day 1
Dose-dependent adverse reaction of Oxaliplatin that often but not always resolves following cessation of therapy
Sensory neuropathy
T or F: FOLFIRI is superior to FOLFOX in efficacy
False
Equal efficacy
Monoclonal antibodies effective in advanced colorectal cancer directed against epidermal growth factor receptor (EGFR)
- Cetuximab
2. Panitumumab
A monoclonal antibody directed against vascular endothelial growth factor (VEGF) that acts as an antiangiogenesis agent used in advanced colorectal cancer in addition to FOLFOX and FOLFIRI
Bevacizumab (Avastin)
Side effects of Bevacizumab
- Hypertension
- Proteinuria
- Increased likelihood of thromboembolic events
In patients with solitary hepatic metastases, from colorectal cancer, without clinical or radiographic evidence of additional tumor involvement, what procedure can be considered to increase 5-year survival rate to 25-30%?
Partial liver resection
In cancer of the ANUS, where do most of the lesions arise?
Anal canal
From anorectal ring to a zone approx halfway between the pectinate (or dentate) line and the anal verge
Carcinomas of anus arising PROXIMAL to pectinate line
Basaloid, cuboidal or cloacogenic tumors
Type of anal cancer occurring in 55% of cases, ulcerate more frequently and arises DISTAL to pectinate line
Squamous cell carcinoma
Development of anal cancer is associated with infection of this virus
Human papillomavirus (HPV)
Anal warts due to infection with human papillomavirus
Condyloma acuminata
How do anal warts progress to neoplasia?
Anal warts –> Anal intraepithelial neoplasia –> Squamous cell carcinoma
T or F: Vaccination against HPV may reduce eventual risk for anal cancer
True
T or F: Anal cancer occurs most commonly in middle-aged persons and more frequent in men.
False
WOMEN
Symptoms of patients with anal cancer
- Bleeding
- Pain
- Sensation of perianal mass
- Pruritus
Treatment for anal cancer
Preferred: Radiation therapy + Chemotherapy (5-FU and Mitomycin C)
If still with residual tumor: Radical surgery (abdominal-perineal resection with lymph node sampling and permanent colostomy)
