110 : Lower GI Cancers Flashcards by Mae Matira

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

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Which type of polyp is premalignant?

Adenomas

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Adenomatous polyps are seen in 30% of middle-aged and 50% of elderly people. What percentage of polyps become malignant?

<1%

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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

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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)

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Characteristics of polyp that can become malignant

Sessile polyps
Villous adenomas
>2.5cm in size

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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

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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

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T or F: Colorectal cancer occurs more often among upper socioeconomic population who live in urban areas.

True

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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)

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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

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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)

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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

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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

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Polyposis coli with appearance of malignant tumors of the central nervous system

Turcot’s syndrome

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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

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Surgical treatment and prevention for polyposis coli

Total colectomy

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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

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Risk of an offspring to develop polyposis coli

50% risk

Screening by annual flexible sigmoidoscopy until age 35 or proctosigmoidoscopy

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Location of polyps in polyposis coli

Cecum to anus

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Definitive diagnosis for polyposis coli

Detection of APC gene mutation from DNA testing

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Rare autosomal recessive syndrome caused by biallelic mutation in the MUT4H gene

MYH-associated polyposis (MAP)

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Recommended surveillance for patients with MYH-Associated Polyposis

Annual to biennial colonoscopic surveillance starting at age 25-30

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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)

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Characteristics of HNPCC

1. Three or more relatives with histologically documented colorectal cancer, one of whom is a first-degree relative of the other two 2. One or more cases of colorectal cancer diagnosed before age 50 in the family 3. Colorectal cancer involving at least two generations

HNPCC is associated with multiple primary cancers. Other associated cancers aside from colorectal cancer include

1. Ovarian CA 2. Endometrial CA 3. 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

1. Oral folic acid supplements 2. Oral calcium supplements 3. Estrogen replacement therapy (decreases IGF-I)

Suggested screening for colorectal cancer by American Cancer Society and NCCN

1. Fecal occult blood testing ANNUALLY + Flexible sigmoidoscopy EVERY 5 years OR 2. 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

1. Cancers can become quite large without resulting in any obstructive symptoms or alteration in bowel habits since the stool passing here is liquid 2. Associated symptoms : Fatigue, palpitation, angina pectoris 3. Hypochromic, microcytic anemia (IDA) 4. Tumors may bleed intermittently

Presenting symptoms of lesions in the transverse and descending colon

1. Abdominal cramping, occasional obstruction, and perforation 2. Radiographs: Annular constricting lesions ("apple-core" or "napkin-ring")

Presenting symptoms of lesions in the rectosigmoid

1. Hematochezia, tenesmus, narrowing of caliber of stool | 2. Anemia is infrequent

Basis of prognosis for colorectal cancer

1. DEPTH of tumor penetration into bowel wall 2. presence of REGIONAL LYMPH NODE involvement 3. 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?

1. Thorough physical exam 2. Biochemical assessment of liver function 3. Measure plasma CEA level 4. 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

1. Semiannual physical examinations and blood chemistry measurements for 5 years 2. Complete colonoscopy post op, if not yet done 3. CEA levels at 3-month intervals 4. Endoscopic surveillance at triennial intervals 5. 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

1. Irinotecan 180mg/m2 as a 90-min infusion on day 1 2. Leucovorin 400mg/m2 as 2-h infusion during irinotecan administration 3. 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

1. Leucovorin (400mg/m2 per day) as 2-h infusion 2. Followed by 5-FU bolus (400mg/m2 per day) and 22-h infusion (1200mg/m2) every 2 weeks 3. 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)

1. 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

1. Hypertension 2. Proteinuria 3. 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

1. Bleeding 2. Pain 3. Sensation of perianal mass 4. 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)