Colorectal cancers
- 2. Epidemiology ➢ MC malignancy of G.I.Tract. ➢ 1.5 lakhs new cases annually.(U.S.A.) ➢ >50,000 annual deaths. ➢ Ranks 3rd in terms of both gender specific annual cancer incidence and mortality. ➢ Large geographic differences, ➢ ~ 7 / lakh in less developed regions. ➢ ~ 55 / lakh well developed regions.
- 3. Epidemiology p Recently, Decreasing mortality of colorectal cancer due to early detection and improvement in medical & surgical care.
- 9. Risk Factors p Extrinsic - ■ Dietary fiber, Meat & Fat ■ Calcium, Vitamins & Micronutrients ■ Aspirin & COX-2 inhibitors ■ Cholecystectomy and Bile Acids ■ Smoking & Alcohol Consumption p Intrinsic - ▪ Personal & Family History ▪ Inflammatory Bowel Disease
- 11. Polyp ➢ Mass that protrudes into the lumen ➢ Subdivided according to - Attachment to bowel wall - Nature - Histological appearance - Neoplastic dignity
- 12. Hyperplastic polyp ➢ Small(3-6mm),sessile mucosal outgrowth. ➢ Found commonly in the large bowel, ➢ predominantly in the rectum & sigmoid. ➢ Reported in 75% of cases over age 60 at autopsy. NOT considered premalignant
- 13. Adenomatous polyp ➢ MC epithelial neoplasm in the colon. ➢ Villous, tubulovillous & tubulous variants. ➢ Pedunculated or sessile. ➢ Malignant potential ➢ villous > tubulovillous > tubulous variants.
- 14. The Haggitt Classification p Useful tool to describe the degree of invasion. level 4
- 16. Hereditary CRC ➢ Inherited Colorectal carcinoma ➢ Familial Adenomatous Polyposis ➢ Attenuated FAP ➢ Hereditary Nonpolyposis Colon Cancer ➢ (Lynch Syndrome) ➢ Hamartomatous Polyposis syndrome ➢ Juvenile Polyposis syndrome
- 17. Non Hereditary CRC ➢ Sporadic CRC ➢ MC of all CRC (~60%) ➢ No family history or inherited predisposition ➢ Commonly above the age of 50 ➢ Familial CRC ➢ 2nd MC (25-30 %) ➢ Least understood pattern of genetic Development ➢ In affected families, CRC develops too frequently to be considered a sporadic CRC
- 18. Screening ➢ Applicable only to asymptomatic people. ➢ Effective screening ➢ Based on adenoma-carcinoma sequence, ➢ take 5-10yrs from the first molecular change to a clinical manifest cancer. ➢ Successful screening programs ➢ Reduce the incidence by 76-90%
- 19. Screening ➢ Fecal Occult Blood Testing (FOBT) ➢ Flexible Sigmoidoscopy ➢ FOBT & Flexible Sigmoidoscopy ➢ Colonoscopy ➢ Air - contrast Barium Enema ➢ CT Colonography ➢ Capsule endoscopy ➢ Stool DNA test
- 20. Fecal Occult Blood Testing ➢ Exam.n of stool for occult (“hidden”) blood ➢ Reduces ➢ CRC mortality - by 33% ➢ metastatic cases - by 50 %
- 21. Fecal Occult Blood Testing ➢ Advantages ➢ Easy of use & noninvasive ➢ Low cost ➢ Good sensitivity with repeat testing ➢ Disadvantages ➢ Low specificity ➢ Not detect most polyps
- 22. Flexible Sigmoidoscopy ➢ Every 5 years screening – ➢ 60-70% reduction in mortality from CRC. ➢ Advantages ➢ Examine colon most at risk. ➢ Very sensitive for polyp detection in left colon ➢ Not require bowel preparation ➢ Disadvantages ➢ Uncomfortable ➢ Slight risk of perforation or bleeding ➢ May miss proximal lesion
- 23. Colonoscopy Most accurate & most complete method for examine the large bowel
- 24. Colonoscopy Determine the circumferential and longitudinal extent of a lesion Ability to take biopsies. Remove synchronous Neoplastic polyps
- 25. Colonoscopy Therapeutic aspects active bleeding an imminent obstruction cauterization, laser ablation, placement of a self-expanding wall stent Turn an emergency situation into an elective one.
- 26. Colonoscopy ➢ Advantages ➢ Examine entire colon ➢ Highly sensitive & specific ➢ Therapeutic ➢ Disadvantages ➢ Uncomfortable ➢ Requires bowel preparation ➢ Risk of perforation or bleeding
- 27. Air-contrast Barium Enema Visualision of anatomic position of a colonic lesion (road map) o Also provides information regarding ■ fistula between colorectum & other pelvic organs.
- 28. Air-contrast Barium Enema Fixed filling defect with destruction of the mucosal pattern in an annular configuration ("apple core") Highly sensitive for detecting polyps >1cm
- 29. Air-contrast Barium Enema ➢ Advantages ➢ Examine entire colon ➢ Through even severely obstructing lesions ➢ Disadvantages ➢ Requires bowel preparation ➢ May miss lesion in the sigmoid colon ➢ Less sensitive for detecting polyps <1cm ➢ Inability to take biopsies.
- 30. CT Colonography ➢ Use of Helical-CT & 3D reconstruction to image the intra-luminal colon.
- 31. CT Colonography ➢ Advantages ➢ Examines entire colon ➢ Noninvasive ➢ Sensitivity as good as colonoscopy ➢ Disadvantages ➢ Requires bowel preparation ➢ Insensitive for small polyps ➢ Minimal experience & data
- 32. Video-capsule ➢ A pill-shaped camera (28 X 11mm) that travels through gut and makes pictures (50,000) of the inner layer (mucosa) of intestine. ➢ Pictures are continuously sent via wireless route (radio waves) to the recorder for 8 hours. ➢ Recorded images have be uploaded on the computer, and a video has be made from them and studied by the doctor. ➢ Can be done in a patient >10 yrs of age including pregnant women.
- 33. Stool DNA Test (sDNA) ➢ Evaluates stool for the presence of altered DNA in the adenoma-carcinoma sequence
- 34. Screening Guidelines For CRC
- 35. Average Risk Population ➢ Initial age - 50yrs. ➢ Recommended Screening Tests: ➢ Annual FOBT ➢ Flexible Sigmoidoscopy every 5y ➢ Annual FOBT & Flexible Sigmoidoscopy every 5y ➢ Air contrast barium enema every 5y ➢ Colonoscopy every 5y
- 36. Adenomatous polyps Initial age – 50yrs. Colonoscopy at first detection followed by at 3yrs. If no further polyps, colonoscopy every 5yrs. Otherwise, colonoscopy every 3yrs. Annual colonoscopy (>5 adenomas)
- 37. Ulcerative colitis, Crohn’s colitis ➢ Initial Age - at diagnosis. ➢ Recommended Screening Test ➢ Colonoscopy with multiple biopsies every 1-2yr
- 38. Familial Adenomatous polyps ➢ Initial age 10-12y (20y in attenuated FAP) ➢ Annual flexible Sigmoidoscopy ➢ Upper endoscopy every 1–3 years after polyps appear
- 39. Hereditary nonpolyposis colon cancer ➢ Initial age 20–25 years ➢ Colonoscopy every 1–2 years ➢ Endometrial aspiration biopsy every 1–2 years
- 40. Familial CRC 1st degree relative ➢ Initial age 40 yrs or 10 yrs before the age of the youngest affected relative ➢ Colonoscopy every 5 yrs ➢ Increase frequency ➢ if multiple family members are affected, especially before 50yrs
- 41. TNM Staging of CRC Tx Cannot be assessed T0 No evidence of cancer Tis Carcinoma in situ T1 Invasion of submucosa T2 Invasion of muscularis propria T3 Invasion of subserosa or into nonperitonealized pericolic /perirectal tissues T4 Invasion of other organs or tissues or perforates the visceral peritoneum.
- 42. TNM Staging of CRC NX Regional lymph nodes cannot be assessed N0 No lymph node metastasis N1 1-3 pericolic or perirectal lymph nodes N2 >3 pericolic or perirectal lymph nodes N3 any lymph node along a major named vascular trunk
- 43. TNM Staging of CRC MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis present
- 44. TNM Staging of CRC Stage TNM 5-Yr Survival I T1-2 N0 M0 70–95% II T3-4 N0 M0 54–65% III Tany N1-3 M0 39–60% IV Tany Nany M1 0–16%
- 46. Physical Examination ➢ Vital signs and temperature ➢ Evidence of cachexia, dehydration, jaundice, Anaemia. ➢ Lymph node enlargements ➢ Palpable primary tumor ➢ Hepatomegaly (liver metastasis?)
- 47. Physical Examination ➢ Abdominal distension ➢ Signs of bowel obstruction ➢ Tympanic bowel sounds ➢ Signs of bowel perforation ➢ Guarding ➢ Local direct and rebound tenderness ➢ Digital Rectal Examination ➢ Proctoscopy
- 48. DRE & Proctoscopy Allows a detailed inspection of the distal rectum and anal canal. The presence of any distal intra-rectal intra-anal or extra luminal mass is recorded.
- 49. Investigations ➢ To assess the large bowel ➢ The primary lesion & concomitant lesions ➢ To determine the metastasis ➢ To assess the patient's operability ➢ (overall condition and co-morbidities).
- 50. Role of TRUS Pretreatment staging ■ TRUS to determine the T and N status. TRUS ■ Highly accurate at assessing tumor depth. ■ Less accurate in diagnosing nodal involvement. ■ Can guide choice of therapy in most patients.
- 51. MRI
- 52. Arrowhead The site of the endorectal coil. Large arrow Demonstrates invasion into the mesorectal fat. Small arrow Points to the radial margin of the mesorectum Transluminal MRI
- 53. Investigations Laboratory and Preoperative Tests ➢ CBC ➢ Electrolytes ➢ Creatinine/blood urea nitrogen (BUN) ➢ Glucose ➢ Liver function tests (alkaline phosphatase, AST, ALT, bilirubin, total protein, albumin) ➢ Coagulation parameters (PT, PTT, INR) ➢ CEA
- 54. Investigations CEA ➢ Main solid tumour marker. ➢ Prognostically important. ➢ Importance in post op period to detect recurrence and metastasis. ➢ Serial values roughly parellel either tumour regression or progression during treatment. ➢ Done every 3 months, upto 3 yrs after surgery.
- 55. Therapy for CRC Colo-Rectal Carcinoma
- 56. Therapy for colonic carcinoma Principles of resection ➢ To remove the primary tumor along with its lymphovascular supply. ➢ The length of bowel resection depends upon the vessels supplying the segment involved. ➢ Resection of minimum 12 lymphnodes is necessary for adequate staging. ➢ En-bloc removal of any adjacent organ or tissue, that has been invaded.
- 57. Therapy for colonic carcinoma Principles of resection ➢ Synchronous lesions / strong family history ➢ Subtotal or total colectomy. ➢ Metachronous tumors ➢ identified during f/up – treated similarly. ➢ On exploration, if metastatic disease is encountered, ➢ the primary tumor should be resected
- 58. Surgery for colonic carcinoma Polyps - carcinoma in situ (high-grade dysplasia) Excised completely. Pathologic margins should be free of dysplasia. If the polyp cannot be removed entirely, segmental resection is recommended. May be removed endoscopically. Should be followed with frequent colonoscopy.
- 59. Surgery for colonic carcinoma Invasive carcinoma in the head of a pedunculated polyp with no stalk involvement completely resected endoscopically. However, lymphovascular invasion, poorly differentiated histology, or tumor within 1 mm of the resection margin, segmental colectomy is then indicated. Invasive carcinoma arising in a sessile polyp extends into the submucosa and is usually best treated segmental colectomy.
- 61. Anastomosis p
- 63. Chemoradiation The goal of adjuvant therapy is to eliminate the micro metastatic disease present at the time of surgery to prevent local recurrence / distant metastases.
- 64. Chemoradiation Preoperative chemoradiation Advantages Tumor shrinkage Increased likelihood of resection A sphincter-sparing procedure Tumor downstaging. Decreased risk to the small intestine. Disadvantages Overtreatment of early stage tumors Impaired wound healing Pelvic fibrosis
- 65. Chemoradiation Postoperative Chemoradiation ■ Accurate pathologic staging ■ Avoids the wound healing problems.
- 66. Adjuvant Chemotherapy Stage II “High risk” for recurrence Stage III Stage IV Indications
- 67. Adjuvant Chemotherapy ➢ FOLFOX Regimen ❖ Oxaliplatin 85 mg/m2 IV day 1 ❖ 5-FU 400mg/m2 IV f/by 600 mg/m2 IV day 1&2. ❖ Leucovorin 200 mg/m2 IV day 1&2. (before 5-FU) ❖ Repeat cycle every 2 weeks for a total 12 cycles.
- 68. Adjuvant Chemotherapy ➢ FOLFIRI Regimen(For Metastatic disease) ❖ Irinotecan 180 mg/m2 IV day 1 ❖ 5-FU 400 mg/m2 IV f/by 2400 mg/m2 IV in 46hrs. ❖ Leucovorin 400 mg/m2 IV days 1 & 2 (before 5-FU) ❖ Repeat cycle every 2 weeks for a total 12 cycles.
- 69. Adjuvant Chemotherapy ➢ FOLFOX+Bevacizumab Regimen + Bevacizumab (10 mg/kg) IV.
- 70. Adjuvant Radiotherapy Indications T4N0/N+, T3N+ disease (excluding mid-sigmoid and mid- transverse colon) T3N0 patients with margins of <1 cm.
- 71. Advanced Colon Carcinoma Hepatic resection of synchronous metastases may be performed as a combined procedure or in two stages. All patients require adjuvant chemotherapy. The remainder of patients with stage IV disease cannot be cured surgically treatment should be palliation. Some patients will respond to chemotherapy, but cure is rare.
- 72. Rectal Carcinoma ➢ The primary goal of surgical treatment Complete eradication of the primary tumor along with the adjacent mesorectal tissue and the superior hemorrhoidal artery pedicle. Cancer removal should not be compromised in an attempt to avoid a permanent colostomy. For tumors located in the extra peritoneal rectum, resection margins are limited by the bony confines of the pelvis and the proximity of the bladder, prostate, and seminal vesicles in men and vagina in women.
- 73. Resection Margins ➢ Distal Margins ➢ 2-cm is acceptable ➢ Proximal Margins ➢ 5-cm is still recommended. ➢ Radial Margins ➢ more critical for local control. In proximal rectal cancers, distal mesorectal excision 5 cm below the lower border of the tumor should be the goal. 0.5 to 1 cm margin chemoradiationRecently,
- 74. Therapy for Rectal carcinoma Stage-Specific Therapy
- 75. Stage I Invasive carcinoma confined to the head of a pedunculated polyp ■ Polypectomy with clear margins. ■ risk of metastasis (<1%).
- 76. Stage I Tumors Amenable to Local Excision T1-2N0 lesion <4 cm in diameter <40% circumference of the lumen <10 cm from dentate line Well to moderately differentiated histology Local control in patients ■ with extensive metastatic disease and poor prognosis.
- 77. Stage I Local excision options: Trans-sphincteric,( Faecal incontinence) Transanal, Transcoccygeal, and Transanal Endoscopic Microsurgery (TEM)
- 80. Stage I Transanal Endoscopic Microsurgery (TEM)
- 81. Stage I • Adjuvant chemotherapy treatment ■ Lymphatic invasion, ■ T1 with poor prognosis features, ■ T2 lesions
- 82. Stage II Chemoradiation + Resection + Total mesorectal resection (TME)
- 83. Surgical options ➢ Sphincter saving surgery ❖ Anterior Resection ❖ Low Anterior Resection + TME ➢ APR
- 84. AR & LAR with TME ➢ Anterior resection means resection of proximal rectum or rectosigmoid above the peritoneal reflection. ➢ Low Anterior resection means resection of rectum below the peritoneal reflection. ➢ Sigmoid colon almost always included. ➢ Entire mesorectum - exised in continuity with the rectum.
- 85. Total Mesorectal Excision A technique that uses sharp dissection along anatomic planes to ensure complete resection of the rectal mesentery during low and extended low anterior resections. TME ➢ associated with less blood loss ➢ less risk to the pelvic nerves and presacral plexus than is blunt dissection. ➢ decreases local recurrence rates ➢ and improves long-term survival rates.
- 87. Anastomosis p Colo-rectal p Colo-anal +/- rectal pouch
- 89. Hand Sewn Circular stapler
- 90. APR ➢ Introduced by Miles
- 91. APR ➢ Indications:- 1. Invasive carcinoma distal third of rectum 2. Persistent or recurrent epidermoid carcinoma of anal canal. 3. Melanoma of the rectum. 4. Locally advanced rectal carcinoma. 5. Pt with recurrent rectal carcinoma amenable to resection.
- 92. Stage III ➢ Neoadjuvant therapy followed by radical resection. OR ➢ Radical surgery with TME
- 93. Stage IV Survival is limited. Isolated hepatic metastases (rare), ■ may be resected for cure in selected patients. Most patients will require palliative procedures.
- 94. Stage IV palliative procedures: Local therapy ■ cautery, endocavitary radiation, or laser ablation ■ to control bleeding or prevent obstruction. Radical resection may be required, ■ but highly morbid procedures such as pelvic exenteration and sacrectomy should generally be avoided.
- 95. Stage IV palliative procedures: Intraluminal stents ■ Useful in the uppermost rectum, ■ but often cause pain & tenesmus lower in the rectum. Proximal diverting colostomy ■ to alleviate obstruction. ■ Mucus fistula - to vent the distal colon.
- 96. To Conclude……. p CRC is a leading cause of death p Early stages are detectable p Screening can prevent CRC
- 97. TAKE HOME MESSAGE “Never ever forget “ DRE in any patient presenting with lower G.I. symptoms
- 98. Thanks for your patience
Editor's Notes
- #5: >55%
- #10: Aging – It is the dominent risk factor.Incidence rising steadily after age 50 yrs.More than 90 % of cases diagnosed are in people older than 50 yrs of age. COX-2 not detectable in normal colon but in 90% of CRCs and 40% of adenomas Hereditary Risk factors-80 % sporadically.20% in known family history of colorectal carcinoma. Environmental and Dietary factorys
- #17: Detail ??