Colo rectal carcinoma
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Colo rectal carcinoma- presented by Dr.Prabhu Dayal Sinwar
![Occurs in three form
Hereditary
Sporadic
Familial
•Family history
•Younge age at oncet
•Presence of other specific
tumors and defects
•Absence of family history
•Generally affect older
population[60-80yr age]
•Isolated colon or rectal
lesion
•Increased risk in which index
case is young[<50yr age]
•Relative is close[first degree
relative]
•20%
FAP-1%
HNPCC-5%
FCC-10-15%
•80%](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)
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Colo rectal carcinoma
- 2. Occurs in three form Hereditary Sporadic Familial •Family history •Younge age at oncet •Presence of other specific tumors and defects •Absence of family history •Generally affect older population[60-80yr age] •Isolated colon or rectal lesion •Increased risk in which index case is young[<50yr age] •Relative is close[first degree relative] •20% FAP-1% HNPCC-5% FCC-10-15% •80%
- 3. 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
- 4. • • • • • • Inflammatory bowel disease eg. UC,Crohns ds. Streptococcus bovis bacteremia Uretero sigmoidostomy Smoking Acromegaly Pelvic irradiation
- 5. decreased risk dietary fiber, Vegetables, Fruits, antioxidant vitamins, NSAIDS, Selenium, Calcium, Hormone replacement therapy
- 9. APC truncation mutation B-catenin level raise Wnt activated cyclin D1 and Myc overexpresion cell proliferation and tumor formation
- 10. FAP cont…. • Autosomal dominant • >100 adenomatous polyp • 5q21 chromosome • <1% all CRC • Periampulary ca duodenum Extra intestinal features Osteomas, desmoid tumor,CHRPE,medulloblastoma [Gardner syn; Turcot syn.] • Diag. – APC gene testing • Rx- prophylactic proctocolectomy with IPAA
- 11. Carcinogenesis
- 12. HNPCC[Hereditary non polyposis colon cancer] mismatch repair (microsatellite instability) pathway
- 13. HNPCC • Autosomal Dominant • Chromosome 2[hMSH2,hMSH6], 3[hMLH1], 7[hPMS2] {MMR gene} • 3-5% of all CRC • Poorly differentiated & mucinous • Signet ring histology Lynch I-CRC only Lynch 2-CRC with asso. Malignancy • • • • Endometrial Gastric Ovarian Muri-Torre synd. Diag. – Family history – detection of germ line mutation in MMR
- 14. Clinical criteria for HNPCC Amsterdam 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 criteria Amsterdam 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
- 15. 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
- 17. Colorectal polyp Neoplast ic polyp Non neoplastic polyp incidence Adenomatous polyp /adenomas 1. Tubular 65-80% 2. Tubulovillous 10-25% 3. villous 5-10% Risk of malignancy 5% 20% 40% 1. Hyperplastic 2. Hamartomatous Cowden's ds Familial juvenile polyposis Peutz jeghers synd. Ruvalcaba –myhre-smith synd. 3. Inflammatory
- 18. 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]
- 19. Clinical feature Right colon Left colon 1. Fungating / cauliflower growth 1. Annular, constricting or stenosing growth 2. Ulcerative lesion leading to chronic insidious blood loss Melena Fatigue Abdominal pain 2. Symptom of obstruction Change in bowel habbit 3. Good prognosis 3. Poor prognosis
- 22. Diagnosis 1. 2. 3. 4. Abdominal and Per-rectal examination Fecal occult blood testing[FOBT] Barium enema Water soluble contrast enema- to establish anatomical level of obstruction 5. Colonoscopy[gold standard] and sigmoidoscopy 6. biopsy 7. Virtual colonoscopy
- 23. 8. MRI-better in rectal ca 9. Ultrasound- trans rectal 10. CECT abdomen and pelvis 11. FDG-PET 12. serum markers (elevated blood levels of carcinoembryonic antigen) 13. molecular detection of APC mutations in epithelial cells, isolated from stools 14. tests under development: detection of abnormal patterns of methylation in DNA isolated from stool cells
- 27. Haggit classification for polyp containing cancer • Acc. To depth of invasion Level o NOT invade muscularis mucosa Level 1 Invade but limited to head of polyp Level 2 Level of neck of polyp Level 3 Any part of stalk Level 4 Invade sub mucosa but above muscularis propria
- 29. Staging
- 30. Staging • TNM stagingPrimary 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
- 31. 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
- 32. Distant metastasis • Mo• M1-distant metastasis • M1a-confined to one organ or site • M1b-more than one organ or site or peritoneum
- 33. Modified Dukes classification stage description A confined to bowel wall B1 partially penetrate the muscularis propria B2 Fully………………………………………………………… C1 Lymph node invasion without penetration of entire bowel wall C2 …………………………………with…………………………………………….. D Distant metastasis
- 34. 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
- 35. 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
- 36. Treatment according to stage • Stage 0[Tis,No,Mo] Endoscopic polypectomy • Stage1[T1,N0,M0] Malignant polyp Segmental colectomy • Stage1&2[T1-3,N0,M0] Localised colon ca Surgical resection • Stage3[any T,N1,Mo] Lymph node metastasis Surgical resection + adjuvant chemo • Stage4[Tany,Nany,M1] Distant metastasis Metastetectomy+chemo
- 37. • 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
- 39. 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
- 40. • Chemotherapy regimen– FOLFOX[5-FU, Leucovorin, Oxaliplatin] • Newest agent-effective for metastatic disease – Cetuximab ,Panitumumab-EGFR inhibitor – Bevacizumab-VEGF inhibitor
- 41. Prognosis • Most important guide to prognosis is STAGE of the disease i.e. depth of penetration and number of LNs involved ADVERSE C/F 1. Younger age < 30 yr 2. Long symptomatology 3. Obstruction/ perforation 4. Location-pelvic and splenic flexure
- 42. • 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
- 43. 5 yr survival following treatment Stage Survival 1 90% 2 75% 3 50% 4 <5%
- 44. 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
- 45. • 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
- 46. Diagnosis • • • • Rigid sigmoidoscopy and biopsy TRUS Endorectal coil MRI CECT
- 47. Treatment Stage o [Tis, No, Mo] Local excision Stage 1[T1-2,No,Mo] Polypectomy Radical 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
- 48. • 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
- 49. THANK YOU