Download - Colo rectal carcinoma
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Colorectal Carcinoma
Presented by-Dr.Prabhu Dayal Sinwar
Guide –Dr . S.P.CHOUHAN
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Occurs in three formHereditary Sporadic Familial•Family history•Younge age at oncet•Presence of other specific tumors and defects
•20%FAP-1%HNPCC-5%FCC-10-15%
•Absence of family history•Generally affect older population[60-80yr age]•Isolated colon or rectal lesion
•80%
•Increased risk in which index case is young[<50yr age]•Relative is close[first degree relative]
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Risk factor• Age [m/c]• Dietary factor
• High animal fat diet• Low fiber diet• Alcohol
• Hereditary syndrome• FAP - germ line APC mutation –accelerated tumor
initiation, 100% risk of CRC• HNPCC-germ line mutation in MMR gene –accelerated
tumor progression,70-80% life time risk of CRC
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• Inflammatory bowel disease eg. UC,Crohns ds.
• Streptococcus bovis bacteremia• Uretero sigmoidostomy• Smoking• Acromegaly• Pelvic irradiation
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dietary fiber,Vegetables,Fruits,antioxidant vitamins,NSAIDS,Selenium,Calcium,Hormone replacement therapy
decreased risk
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Pathogenesis
Normal colonic epithelium
Dysplastic aberrant crypt
foci
Early adenomas
Intermediate adenomas Late adenomas Carcinomas Metastasis
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FAP[Familial Adenomatous Polyposis]
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APC truncation mutation B-catenin level raise Wnt activatedcyclin D1 and Myc overexpresioncell proliferation and tumor formation
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FAP cont….
• Autosomal dominant• >100 adenomatous polyp• 5q21 chromosome• <1% all CRC• Periampulary ca duodenumExtra intestinal featuresOsteomas, desmoid tumor,CHRPE,medulloblastoma[Gardner syn; Turcot syn.]
• Diag. – APC gene testing• Rx- prophylactic proctocolectomy with IPAA
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Carcinogenesischromosome instability pathway
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HNPCC[Hereditary non polyposis colon cancer]
mismatch repair (microsatellite instability) pathway
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HNPCC• Autosomal Dominant• Chromosome 2[hMSH2,hMSH6], 3[hMLH1], 7[hPMS2] {MMR
gene}• 3-5% of all CRC• Poorly differentiated & mucinous• Signet ring histologyLynch I-CRC onlyLynch 2-CRC with asso. Malignancy
• Endometrial• Gastric • Ovarian• Muri-Torre synd.
Diag.– Family history– detection of germ line mutation in MMR
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Clinical criteria for HNPCCAmsterdam criteria
At least three relative with colon cancer – One is the first degree relative of other two– Two successive generation– One case diagnose before 50 yr age– FAP excluded
Modified Amsterdam criteria– All above with asso. Of HNPCC (other malignancy)
Bethesda criteriaAmsterdam criteria OR one of the following– Two cases of HNPCC – asso cancer in one patient including synchronous or
metachronous cancer – Colon cancer and a first degree relative with HNPCC asso cancer and/or
adenoma– Colon or endometrial cancer diagnosed before age 45 yr– Right side colon cancer that have undifferentiated pattern or signet cell
histopathology– Adenomas diagnosed before 40 yr
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Screening recommendation
• FAP– Colonoscopy annually– Beginning at age 10-12yr
• HNPCC– Colonoscopy
– every 2 yr beginning age 20yr– Annually after age 40yr or 10yr younger than earliest case in
family
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Colorectal polypNeoplastic polyp
incidenceRisk of malignancy
Non neoplastic polyp
Adenomatous polyp /adenomas
1. Tubular2. Tubulovillous3. villous
65-80%10-25%5-10%
5%20%40%
1. Hyperplastic2. Hamartomatous
Cowden's dsFamilial juvenile polyposisPeutz jeghers synd.Ruvalcaba –myhre-smith synd.
3. Inflammatory
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Site of Carcinoma
Rectum-38%{M/C}Sigmoid colon-21%Caecum-12%
Transverse colon -5.5%Ascending colon-5%Descending colon-4%
Splenic flexure-3%[L/C]
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Clinical feature
Right colon
1. Fungating / cauliflower growth
2. Ulcerative lesion leading to chronic insidious blood loss
MelenaFatigueAbdominal pain
3. Good prognosis
Left colon
1. Annular, constricting or stenosing growth
2. Symptom of obstructionChange in bowel habbit
3. Poor prognosis
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Diagnosis
1. Abdominal and Per-rectal examination2. Fecal occult blood testing[FOBT]3. Barium enema4. Water soluble contrast enema- to establish
anatomical level of obstruction5. Colonoscopy[gold standard] and sigmoidoscopy6. biopsy7. Virtual colonoscopy
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8. MRI-better in rectal ca9. Ultrasound- trans rectal10. CECT abdomen and pelvis11. FDG-PET12. serum markers (elevated blood levels of
carcinoembryonic antigen)13. molecular detection of APC mutations in epithelial
cells, isolated from stools14. tests under development: detection of abnormal
patterns of methylation in DNA isolated from stool cells
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Haggit classification for polyp containing cancer
• Acc. To depth of invasionLevel o
Level 1
Level 2
Level 3
Level 4
NOT invade muscularis mucosa
Invade but limited to head of polyp
Level of neck of polyp
Any part of stalk
Invade sub mucosa but above muscularis propria
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Staging
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Staging
• TNM staging-Primary tumor-• Tx-cannot be assessed• To-no evidence of primary tumor• Tis-carcinoma in situ-intraepithelial or invasion of lamina
propria• T1- tumor invade sub mucosa• T2-muscularis propria• T3-into peri colorectal tissue• T4a-penetrate surface of visceral epithelium• T4b-invade or adherent to other organ or structure
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Regional lymph node-• Nx-• N0-• N1-one to three• N1a-one• N1b-two to three• N2-four or more• N2a-four to six• N2b-seven or more
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Distant metastasis• Mo-• M1-distant metastasis• M1a-confined to one organ or site• M1b-more than one organ or site or
peritoneum
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Modified Dukes classificationstage description
A
B1
B2
C1
C2
D
confined to bowel wall
partially penetrate the muscularis propria
Fully…………………………………………………………
Lymph node invasion without penetration of entire bowel wall
…………………………………with……………………………………………..
Distant metastasis
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Systemic Metastasis
• Incidence related to the depth of invasion• Liver > lung
Hepatic Extra hepatic
•5-10 % undergo curative liver resection with upto 50% long term survival•Synchronous metastasis have poor prognosis•Recurrence is common•CEA testing every 3mt for 2yr after hepatic resection
•Pulmonary metastasis•Ovarian metastasis
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Treatment
• Surgical resection the only curative treatment
• Likelihood of cure is greater when disease is
detected at early stage
• Early detection and screening is of pivotal
importance
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Treatment according to stage• Stage 0[Tis,No,Mo]
• Stage1[T1,N0,M0]Malignant polyp
• Stage1&2[T1-3,N0,M0]Localised colon ca
• Stage3[any T,N1,Mo]Lymph node metastasis
• Stage4[Tany,Nany,M1]Distant metastasis
Endoscopic polypectomy
Segmental colectomy
Surgical resection
Surgical resection + adjuvant chemo
Metastetectomy+chemo
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• Right hemicolectomy Caecum, ascending colon, hepatic flexure
•Extended right hemicolectomy
Transverse colon lesion
•Left hemicolectomy Tumor of descending colon
•sigmoidectomy Sigmoid colon tumor
•Abdominal colectomy [subtotal/total]
Multiple primary tumor, HNPCC, occasionaly in completely obstructing sigmoid cancer
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Indication of chemo therapy
• Stage2 with at least one poor prognostic indicator eg.– Insufficient lymph node sampling[<12 node
resected]– T4 lesion– Poor differentiated histology– Bowel perforation
• Stage3• Stage4
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• Chemotherapy regimen-– FOLFOX[5-FU, Leucovorin, Oxaliplatin]
• Newest agent-effective for metastatic disease– Cetuximab ,Panitumumab-EGFR inhibitor– Bevacizumab-VEGF inhibitor
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Prognosis
• Most important guide to prognosis is STAGE of the disease i.e. depth of penetration and number of LNs involved
ADVERSE C/F1. Younger age < 30 yr2. Long symptomatology3. Obstruction/ perforation4. Location-pelvic and splenic
flexure
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• ADVERSE PATHOLOGY
1. Disease stage
2. High grade
3. Colloid/ Signet ring cell-mucin production
4. Venous Invasion
5. Perineural invasion
6. Aneuploidy
7. ↑↑ CEA/ collagen
8. Diminished stromal immune reaction
9. P53 gene mutation
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5 yr survival following treatmentStage Survival
1 90%
2 75%
3 50%
4 <5%
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Follow up
• Stage 1-– Colonoscopy 1yr after operation then every 5yr– CEA level –every 3mt during first 2yr
• Stage 2-– CEA level every 3mt for 2yr, every 6mt for a total
of 5yr– Annual CT scan of abdo and chest for 3yr
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Ca Rectum• Share many genetic, biological, and
morphologic characteristic of colon ca• Age of presentation >55yr• Bleeding is earliest and most common
symptom• Other sym.-
– Sense of incomplete defecation– Tenesmus and spurious diarrhea– Bloody slime
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Diagnosis
• Rigid sigmoidoscopy and biopsy• TRUS• Endorectal coil MRI• CECT
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TreatmentStage o [Tis, No, Mo] Local excision
Stage 1[T1-2,No,Mo] PolypectomyRadical resection
Stage 2[T3-4,No,Mo] Pre op chemo radiation + radical resection
Stage 3[Tany,NoMo] Pre op chemo radiation + radical resection
Stage 4 [Tany,NanyM1]
Palliative procedure
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• Low anterior resection– >5cm above dentate line
• Abdomino perineal resection– At or below 5cm from dentate line
• Hartmann's procedure– For elderly or severely unstable pt
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THANK YOU