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Presentation on theme: "UPPER GI BLEEDING: COLON CANCER GROUP A BGD February 1, 2010."— Presentation transcript:


2 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 colon o Commonly ulcerate, leading to chronic, insidious blood loss without a change in the appearance of the stool Tumors of the ascending colon o Fatigue, palpitations, angina pectoris o Hypochromic, microcytic anemia indicative of iron deficiency 2

3 Clinical Manifestations Transverse and descending colon o Tend to impede the passage of stool o 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

4 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

5 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

6 Pathophysiology 6 Most colorectal cancers, regardless of etiology, arise from adenomatous polyps. Polyp - a grossly visible protrusion from the mucosal surface o Non-neoplastic hamartoma (juvenile polyp) o Hyperplastic mucosal proliferation (hyperplastic polyp) o Adenomatous polyp – premalignant Only a minority of such lesions becomes cancer

7 Pathophysiology 7 Molecular changes o 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

8 Pathophysiology 8

9 Clinically, the probability of an adenomatous polyp becoming a cancer depends on: o Gross appearance of the lesion o Histologic features o Size Adenomatous polyps: o Pedunculated (stalked) o Sessile (flat-based) –Cancers develop more frequently in sessile polyps 9

10 Pathophysiology Histologically, adenomatous polyps may be: o Tubular o Villous (i.e. Papillary) –Most are sessile- become malignant more than three times as often as tubular adenomas o Tubulovillous 10

11 Risk Factors Advanced age Diet: animal fat History of cancer Polyps, particularly adenomatous polyps Hereditary syndromes o Polyposis coli o 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 patient o Advanced age (78 years old) o Smoking (19 pack years) 11

12 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 resistance o “Western” diets, physical inactivity- higher prevalence of obesity Obese persons o Insulin resistance  increased circulating levels of insulin  higher circulating concentrations of insulin-like growth factor type I  stimulate proliferation of the intestinal mucosa 12

13 Risk Factors Hereditable (Autosomal Dominant) Gastrointestinal Syndromes 13 SyndromeDistribution of PolypsHistologic TypeMalignant PotentialAssociated Lesions Familial adenomatous polyposis Large intestineAdenomaCommonNone Gardner's syndrome Large and small intestines AdenomaCommon Osteomas, fibromas, lipomas, epidermoid cysts, ampullary cancers, congenital hypertrophy of retinal pigment epithelium Turcot's syndromeLarge intestineAdenomaCommonBrain tumors Non-polyposis syndrome (Lynch syndrome) Large intestine (often proximal) AdenomaCommonEndometrial and ovarian tumors Peutz-Jeghers syndrome Small and large intestines, stomach HamartomaRare Mucocutaneous pigmentation; tumors of the ovary, breast, pancreas, endometrium Juvenile polyposisLarge and small intestines, stomach Hamartoma, rarely progressing to adenoma RareVarious congenital abnormalities

14 Diagnostic Procedures 14 Screening o 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

15 Diagnostic Procedures Digital rectal examination o 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

16 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 16

17 Diagnostic Procedures 17 Biopsy o 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

18 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

19 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

20 Diagnostic Procedures Air-contrast barium enema o 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

21 Diagnostic Procedures Endoscopic ultrasound o To evaluate the gastrointestinal tract o Improves tumor characterization, and enables more precise TNM staging 21

22 Diagnostic Procedures Pre-operative elevation of the plasma carcinoembryonic antigen (CEA) level predicts eventual tumor recurrence 22

23 Management Lower GI bleeding o Stable patients may undergo appropriate diagnostic procedures to determine the source of bleeding o 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 cancer o Whether the cancer has recurred o General health status of the patient 23

24 Management STAGEDESCRIPTIONTREATMENT 0Cancer 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 1Cancer has grown through several layers of the colon, but has not spread outside the colon wall Surgical resection 2Cancer 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

25 Management STAGEDESCRIPTIONTREATMENT 3Cancer 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

26 Management Surgery Pre-operative Procedures Thorough PEChest X-ray Liver Function Plasma CEA level Colonoscopy 26

27 Management Surgery Intraoperative Procedures Laparotomy Inspection of the liver, pelvis, and hemidiaphragm Palpation of the full length of the large bowel TOTAL RESECTION OF THE TUMOR 27

28 Management Surgery Post-operative Procedures RecoverySemi-annual PEColonoscopy Yearly blood chemistry measurements Plasma CEA levels at 3-month intervals 5 years 28

29 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

30 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

31 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 therapy o FOLFIRI = FOLFOX 31

32 Management Chemotherapy o Monoclonal antibodies –Effective for advanced colorecatal cancer –Cetuximab and Panitumumab- directed against EGFR –Bevacizumab- directed against VEGF; anti- angiogenesis 32

33 Management Radiotherapy o Not effective in the primary treatment of colon cancer o May 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

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