Upload
dion-harrup
View
218
Download
1
Tags:
Embed Size (px)
Citation preview
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 deficiency 2
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")
3
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
4
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
5
Pathophysiology
6
• 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
7
• 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
8
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
9
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
10
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)
11
Risk Factors
• Dieto Upper socioeconomic populations o Japan: increased incidence of colorectal cancer since they adopted a
“western” diet
• Animal fatso 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
12
Risk Factors Hereditable (Autosomal Dominant) Gastrointestinal Syndromes
13
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 tumors
Non-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
14
• 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
15
Diagnostic Procedures• Hemoccult blood test
o Detects occult fecal blood
• Colonoscopyo 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
16
Diagnostic Procedures
17
• 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
18
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
19
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
20
Diagnostic Procedures
• Endoscopic ultrasoundo To evaluate the
gastrointestinal tract o Improves tumor
characterization, and enables more precise TNM staging
21
Diagnostic Procedures
• Pre-operative elevation of the plasma carcinoembryonic antigen (CEA) level predicts eventual tumor recurrence
22
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
23
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
24
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
25
Management
• Surgery Pre-operative Procedures
Thorough PE
Chest X-ray
Liver Function
Plasma CEA level
Colonoscopy
26
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
27
Management• Surgery Post-operative Procedures
Recovery
5 years
Semi-annual PE
Colonoscopy
Yearly blood chemistry measurements
Plasma CEA levels at 3-month intervals
28
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
29
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
30
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
31
Management• Chemotherapy
oMonoclonal antibodies– Effective for advanced colorecatal cancer– Cetuximab and Panitumumab- directed
against EGFR– Bevacizumab- directed against VEGF; anti-
angiogenesis
32
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
33