UPPER GI BLEEDING: COLON CANCER

GROUP ABGD February 1, 2010

Clinical Manifestations• Cecum and ascending colon

o May become quite large without resulting in any obstructive symptoms or noticeable alterations in bowel habits

• Lesions of the right colono Commonly ulcerate, leading to chronic,

insidious blood loss without a change in the appearance of the stool

• Tumors of the ascending colono Fatigue, palpitations, angina pectoris o Hypochromic, microcytic anemia indicative of

iron deficiency2

Clinical Manifestations• Transverse and descending colon

o Tend to impede the passage of stoolo Abdominal cramping, occasional obstruction,

perforation• Rectosigmoid

o Hematochezia, tenesmus, narrowing of the caliber of stool

o Anemia is an infrequent finding• Random fecal occult blood test may be negative

o Cancer may bleed intermittently• Radiographs of the abdomen often reveal

characteristic annular, constricting lesions ("apple-core" or "napkin-ring")

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Clinical Manifestations• Patient Correlation

o Hematochezia– Chief complaint– 6 hours PTA passed out half a tsp of blood

after defecation– 4 hours PTA 1 tbsp of blood– 30 minutes PTA 2 cups of fresh blood– Rectal exam showed fresh blood on

examining finger

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Clinical Manifestations• Patient Correlation

o Impeded passage of stool– Constipation for several years

o Palpitations– Sitting HR 110 beats/min– Supine HR 90 beats/min– Felt dizzy, had cold clammy perspiration

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Pathophysiology

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• Most colorectal cancers, regardless of etiology, arise from adenomatous polyps.

• Polyp - a grossly visible protrusion from the mucosal surfaceo Non-neoplastic hamartoma (juvenile polyp)o Hyperplastic mucosal proliferation (hyperplastic

polyp)o Adenomatous polyp – premalignant

• Only a minority of such lesions becomes cancer

Pathophysiology

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• Molecular changeso Mutational activation of an oncogene followed by and

coupled with the loss of genes that normally suppress tumorigenesis– Point mutations in the K-ras protooncogene– Hypomethylation of DNA, leading to gene activation– Loss of DNA (allelic loss) at the site of a tumor-suppressor gene

[the adenomatous 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 deleted in colorectal cancer (DCC) gene]

– Allelic loss at chromosome 17p, associated with mutations in the p53 tumor-suppressor gene

Pathophysiology

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Pathophysiology

• Clinically, the probability of an adenomatous polyp becoming a cancer depends on:o Gross appearance of the lesiono Histologic featureso Size

• Adenomatous polyps:o Pedunculated (stalked) o Sessile (flat-based)

– Cancers develop more frequently in sessile polyps

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Pathophysiology

• Histologically, adenomatous polyps may be:o Tubularo Villous (i.e. Papillary)

– Most are sessile- become malignant more than three times as often as tubular adenomas

o Tubulovillous

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Risk Factors• Advanced age• Diet: animal fat• History of cancer• Polyps, particularly adenomatous polyps• Hereditary syndromeso Polyposis colio Non-polyposis syndrome (Lynch

syndrome)• Inflammatory bowel disease• Infection (viral exposure, Streptococcus

bovis bacteremia)• Uterosigmoidoscopy• Physical inactivity• Smoking/tobacco use• Alcohol• Exogenous hormones• Environmental factors

• Present in the patiento Advanced age (78 years

old)o Smoking (19 pack years)

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Risk Factors• Diet

o Upper socioeconomic populations o Japan: increased incidence of colorectal cancer since they adopted a

“western” diet• Animal fats

o Red meats and processed meat increased proportion of anaerobes in the gut microflora conversion of normal bile acids into carcinogens

• Insulin resistanceo “Western” diets, physical inactivity- higher prevalence of obesity

• Obese personso Insulin resistance increased circulating levels of insulin higher

circulating concentrations of insulin-like growth factor type I stimulate proliferation of the intestinal mucosa

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Risk Factors Hereditable (Autosomal Dominant) Gastrointestinal Syndromes

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Syndrome Distribution of Polyps Histologic Type Malignant Potential Associated Lesions

Familial adenomatous

polyposis

Large intestine Adenoma Common None

Gardner's syndrome

Large and small intestines

Adenoma Common Osteomas, fibromas, lipomas, epidermoid cysts, ampullary cancers, congenital hypertrophy of retinal pigment epithelium

Turcot's syndrome Large intestine Adenoma Common Brain tumorsNon-polyposis

syndrome (Lynch syndrome)

Large intestine (often proximal)

Adenoma Common Endometrial and ovarian tumors

Peutz-Jeghers syndrome

Small and large intestines, stomach

Hamartoma Rare Mucocutaneous pigmentation; tumors of the ovary, breast, pancreas, endometrium

Juvenile polyposis Large and small intestines, stomach

Hamartoma, rarely progressing to

adenoma

Rare Various congenital abnormalities

Diagnostic Procedures

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• Screeningo Goal: earlier detection of localized,

superficial cancers in asymptomatic individuals to increase the surgical cure rate

o Candidates:– 50 years old– Family history of the disease in first-degree

relatives

Diagnostic Procedures

• Digital rectal examinationo Part of any routine

physical evaluation in adults older than age 40

o An inexpensive maneuver for the detection of masses in the rectum

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Diagnostic Procedures• Hemoccult blood test

o Detects occult fecal blood • Colonoscopy

o Superior to double-contrast barium enema

o has a higher sensitivity for detecting villous or dysplastic adenomas or cancers than the strategy employing occult fecal blood testing and flexible sigmoidoscopy

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Diagnostic Procedures

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• Biopsyo During a colonoscopy, several biopsies

(each at different locations in the colon and rectum) may be taken

o Used to diagnose cancer or estimate how far cancer has spread

o Used to obtain bits of tissue to be checked in the laboratory for signs of cancer or other diseases

Diagnostic Procedures• Proctosigmoidoscopy

o Based on the observation that 60% of early lesions are located in the rectosigmoid

• Flexible, fiberoptic sigmoidoscopes o To visualize the colon for up

to 60 cm, which enhances the capability for cancer detection

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Diagnostic Procedures• Virtual colonoscopy

o Computed tomography colography

o A method under study to examine the colon by taking a series of x-rays and using a high-powered computer to reconstruct 2-D and 3-D pictures of the interior surfaces of the colon from these x-rays

o Pictures can be saved, manipulated to better viewing angles, and reviewed after the procedure, even years later

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Diagnostic Procedures• Air-contrast barium

enemao Highly sensitive for

detecting polyps greater than 1 cm in diameter

o After the barium passes through the intestine, air will then be pumped into it

o Using the barium, the technician is able to get a clear picture of the lining of the intestine from multiple angles

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Diagnostic Procedures

• Endoscopic ultrasoundo To evaluate the

gastrointestinal tract o Improves tumor

characterization, and enables more precise TNM staging

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Diagnostic Procedures

• Pre-operative elevation of the plasma carcinoembryonic antigen (CEA) level predicts eventual tumor recurrence

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Management

• Lower GI bleedingo Stable patients may undergo appropriate diagnostic

procedures to determine the source of bleedingo Unstable patients

– Appropriate fluid and electrolytes– Once stable, determine the source of bleeding for appropriate

management

• Colon cancer treatment options depends on:o Stage of the cancero Whether the cancer has recurredo General health status of the patient

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Management

STAGE DESCRIPTION TREATMENT

0 Cancer has not grown beyond the inner lining of the colon

• Polypectomy or local excision through the colonoscope• Colon resection if the tumor is too big to be removed by local excision

1 Cancer has grown through several layers of the colon, but has not spread outside the colon wall

Surgical resection

2 Cancer has grown through the wall of the colon and may extend into nearby tissue; no spread to the lymph nodes

• Surgical resection is usually the only treatment needed• Radiation and chemotherapy for cancers likely to recur

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Management

STAGE DESCRIPTION TREATMENT

3 Cancer has spread to nearby lymph nodes, but has not yet spread to other parts of the body

• Surgical resection is the first treatment• Adjuvant chemotherapy with 5-FU and leucovorin• Radiation therapy: if cancer was large enough to grow into adjacent tissues

4 and Recurrent

colon cancer

Metastasis: liver, lungs, peritoneum, ovaries

• Segmental resection (palliative)• Palliative chemotherapy and radiotherapy

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Management

• Surgery Pre-operative Procedures

Thorough PE

Chest X-ray

Liver Function

Plasma CEA level

Colonoscopy

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Management

• Surgery Intraoperative Procedures

Laparotomy

Inspection of the liver,

pelvis, and hemidiaphrag

m

Palpation of the full length

of the large bowel

TOTAL RESECTION OF THE TUMOR

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Management• Surgery Post-operative Procedures

Recovery

5 years

Semi-annual PE

Colonoscopy

Yearly blood chemistry measurements

Plasma CEA levels at 3-month intervals

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Management• Surgery Post-operative Procedures

Recovery

CT scans of the abdomen - annually for the first three

postoperative years

Endoscopic or radiographic surveillance of the large bowel

- 3 years interval

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Management• Chemotherapy

o 5-FU– Partial response in 15-20% of patients– Backbone of treatment– IV or oral (capecitabine)- similar efficacy

o 5-FU + folinic acid (leucovirin)– Improves efficacy; three-fold improvement in

partial response– Enhances binding to thymidylate synthase

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Management• Chemotherapy

o 5-FU + LV + Irinotecan (FOLFIRI regimen)– Topoisomerase 1 inhibitor– Improves response rates and survival of

patients with metastatic disease– Adverse effect: diarrhea

o 5-FU + LV + Oxiplatin (FOLFOX regimen)– Platinum analogue– Improves response rate– Adverse effect: dose-dependent neuropathy,

resolves following cessation of therapyo FOLFIRI = FOLFOX

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Management• Chemotherapy

oMonoclonal antibodies– Effective for advanced colorecatal cancer– Cetuximab and Panitumumab- directed

against EGFR– Bevacizumab- directed against VEGF; anti-

angiogenesis

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Management• Radiotherapy

o Not effective in the primary treatment of colon cancer

oMay be recommended for prevention of regional recurrences after surgical resections (stage 2 or 3)

o Pre-operatively: may be indicated for potentially large, unresectable tumors (to shrink them) and permit subsequent surgical removal

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