colon cancer full detailed presentation.pptx

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1. Colon cancer

2. Physiologic herniation through the umbilicus Prearterial / Postarterial / Embryology

3. Normal rotation of gut 4 th week Loop formed by midgut 5 th week Rotation of midgut and extracoelomic position 12 th week Orderly return of intestinal loops and further rotation of 180 degrees in counterclockwise direction . Final stage Descent of cecum and fixation of ascending colon to posterior parietal peritoneum

4. Surgical anatomy

5. 5 cm 10 cm 50 cm 10 cm 50 cm

6. Length - 150 cm Ascending and descending colons - retroperitoneally located Greatest caliber - 7.5 cm at the cecum Least caliber - 2.5 cm at the rectosigmoid junction

7. How to differentiate large from small bowel? Taeniae coli Haustra coli Appendices epiploicae

8. Cecum Mobile Complete covering of peritoneum Cecum and ascending colon are related posteriorly to psoas major muscle nerves (lateral femoral cutaneous, femoral, genitofemoral ) gonadal arteries and veins Ureter

9. Inferior ileocecal fold – Avascular Fold of Treves Cecal fundus Gerlach’s valve

10. Ileocecal valve Posteromedial wall of the cecum Prevents reflux Closed-loop obstruction

11. Ascending Colon Short mesentery C overed anteriorly by the peritoneum Jackson's membrane 12 to 20 cm in length

12. Hepatic flexure Lower than splenic flexure Cystocolic ligament H epatocolic ligament

13. Transverse colon 50 cm length Completely covered with peritoneum Supracolic and Infracolic compartments of the peritoneal cavity

14. Transverse Mesocolon and greater omentum

15. Root of transverse mesocolon

16. S plenic flexure H igher than the hepatic flexure P hrenicocolic ligament A dhesions to lower pole of spleen

17. Descending Colon 10 to 25 cm long Relations Q uadratus lumborum muscle L eft adrenal gland Left kidney and left ureter Left gonadal vessels Iliohypogastric and ilioinguinal nerve

18. Mobilization of the descending colon W hite line of Toldt Important surgical plane V ulnerable are the left ureter and the left gonadal vessels

19. Sigmoid Colon 40 cm "S" shape Two portions I liac portion P elvic portion, which is mobile

20. Sigmoid mesocolon & I nter-sigmoid fossa Inverted V-shaped attachment S uperior rectal vessels Landmark for identification of the ureter

21. Arterial Supply

22. Superior Mesenteric Artery A rtery of the midgut At the level of the L1 vertebra Cecum and the ascending colon ileocolic and right colic arteries Transverse colon middle colic artery

23. I leocolic artery I leal and colic branches Colic branch anastomose with the right colic artery appendicular artery - end artery

24. R ight colic artery D escending branch A scending branch Mainly arise from SMA Can also arise from ielocolic artery (or) MCA

25. M iddle colic artery (MCA) B ranch of the SMA (can also arise from Inferior pancreatico -duodenal or RHA or Jejunal artery) A vascular window in the transverse mesocolon Lower border of pancreas neck

26. Inferior Mesenteric Artery Branches of the Inferior mesenteric artery Left colic artery Sigmoid arteries Superior rectal artery Accessory middle colic artery (38%)

27. L eft colic artery Ascending branch & descending branch M eandering artery or arc of Riolan Intact left colic artery with collaterals - colon interposition procedure Splenic flexure - vulnerable to ischemic injury – Griffith’s point

28. Marginal Artery of Drummond

29. Critical Point of Sudeck J ust above the origin of the last sigmoid artery

30. The long vasa recta supply - at the antimesenteric border. The short supply - mesocolic two-thirds of the colonic circumference

31. Venous Drainage

32. G astrocolic trunk Right gastroepiploic vein C olic vein A nterior superior pancreaticoduodenal vein

33. Lymphatic Drainage

34. Carcinoma colon

35. Colon cancer Epidemiology : maximum incidence – west lowest incidence in south central asia 3 rd most common cancer in men 2 nd most common in women world wide 3 rd most common cause of cancer related death world wide

36. etiology Colonic cancer can occur in: Hereditary Familial Sporadic (MC) Hereditary – younger age group with family history (HNPCC & FAP) Familial – runs in families and index case being young (< 50yrs) Sporadic – occurs in absence of family history, usally seen in elderly(>60 yrs)

37. Risk factors: Non Modifiable: Age – Bimodal distribution IBD Family history Modifiable risk factors: Dietary fat Fibre deficiency diet Alcohol Smoking Sedentary lifestyle Obesity Radiation

38. Polyposis syndromes: Classification: Familial Adenomatous Polyposis syndrome a. FAP b. Variants of FAP 1. Gardners syndrome 2. Turcot syndrome 3. Attenuated FAP Familial Hamartomatous polyposis syndromes a. Peutz Jeghers syndrome b. Juvenile polyposis syndromes c. Cowdens syndrome d. Ruvalcaba - Myhre -Smith ( Bannayan-Zonana ) syndrome

39. Fap /Gardner syndrome: Autosomal dominant APC gene 100-1000s of colorectal polyps Duodenal adenomas, Gastric polyps Osteomas , Desmoid tumors & Epidermoid cysts CHRPE (Congenital Hypertrophy of retinal pigment epithelium) CRC incidence risk – 100% Other cancers with increased risk - periampullary region - thyroid, CNS tumors - hepatoblastoma

40. Specimen of total colectomy showing FAP

41. Mandubular Osteomas and its Radiological image

42. Turcot syndrome Autosomal dominant APC, MLH1, PMS2 Few colorectal polyps Cerebellar medulloblastoma and Glioblastomas Increased risk for Colorectal carcinoma and brain tumors

43. Cowden syndrome Autosomal dominant PTEN ( chr 10q) Mucocutaneous lesions, thyroid adenomas and goitre Fibroadenomas and fibrocystic disease of breast Uterine leiomyomas and Macrocephaly Increased risk for Ca colon 10% risk for thyroid cancers 50% risk for breast adenocarcinoma

44. Mucocutaneous lesions Colonic polyps

45. Familial juvenile polyposis : Autosomal dominant SMAD4 (DRC4) chr 10q Juvenile polyps >10 through out the GI tract Malrotation , Hydrocephalus, Meckels diverticulum , Mesentaric lymphangioma and caridac lesions Increased risk of CRC, gastric and duodenal cancer

46. Peutz-jeghers syndrome: Autosomal dominant STK11 ( chr 19p) Small number of polyps in GI tract (MC in small intestine) Pigmented lesions of skin Benign and malignant genital tumors Increased risk factor for - GI malignancy - Pancreatic cancer - Ca Cervix

47. Screening for FAP: Flexible proctosigmoidoscopy – 10-12 years of age - repeat every 1-2 years until 35 years of age - repeat every 3 years after 35 years of age Upper GI endoscopy every 1-3 years starting when polyps first identified Consider brain imaging in turcot syndrome Consider mammography in cowden at 30 years of age and repeat annually

48. HNPCC Heriditary NON POLYPOSIS colon cancer Also known as Lynch syndrome Autosomal dominant MLH1, MSH2, MSH6, PMS1, PMS2 Small number of colorectal polyps Muir-Torre variant- -sebaceous adenomas - keratocanthomas -sebaceous epitheliomas - bassal cell epitheliomas Sebaceous adenoma Keratocanthoma

49. HNpcc contd … Increased risk of -70-80% life time risk for CRC - endometrial cancer, ovarian cancer - gastric cancer, small bowel cancer - transistional cell carcinoma of ureters SCREENING recommendations : Colonoscopy at age 20-25 years - Repeat every 1-3 years TVS or endometrial aspiration at age 20-25 years - Repeat annually

50. Hnpcc contd.. Amsterdam Criteria II :- clinical criteria for HNPCC At least three relatives with HNPCC and all of the following: • One affected person is a first-degree relative of the other two affected persons • Two successive generations affected • At least one case of colon cancer diagnosed before the age of 50 years • FAP excluded

51. Colorectal polyps: Classification based on gross appearance : - Pedunculated - Sessile Classification based on histological appearance : - Tubular adenoma (most common) - Villous adenoma (more malignant potential) - Tubulovillous adenoma

52. Pedunculated adenomatous polyp Sessile adenomatous polyp (tubular adenoma)

53. Villous adenoma Risk of adenoma to carcinoma : Tubular polyp <1 cm - 5% Tubular polyp >2 cm – 35% Villous polyp > 2 cm – 50%

54. Haggitts classification: Proposed for polyps containing cancer Based on depth of invasion of carcinoma Level 0: does not invade the muscularis mucosae (CIS) Level 1: invades through the muscularis mucosae into the submucosa but is limited to the head of the polyp Level 2: invades the level of the neck of the polyp Level 3 : invades any part of the stalk Level 4: invades into the submucosa of the bowel wall below the stalk of the polyp but above the muscularis propria

55. Haggitt classification:

56. screening To detect adenomatous polyps and cancer - colonoscopy every 10 years - flexible sigmoidoscopy evey 5-10 years - CT colonography every 5 years Modalities that primarily detect cancer – stool based - Guaiac based testing annually - Fecal immunochemical test (FIT) (stool DNA) every 3 years

57. Hyperplastic polyps Most common colonic polyp Predominant in right colon More common in older women and smokers 90% are < 3mm , hence no neoplastic potential Cells show dysmaturation and hyperplasia Hyperplastic polyp. Elongated crypts reveal a serrated (saw-toothed) or star-shaped appearance

58. genetics Tumor suppressor genes (gate keeper genes) - APC (5q21) - FAP and its variants - p 53 (17p) – Guardian of genome Mismatch repair genes:( Care taker genes) - MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2 - responsible for 10-15% of sporadic and 95% of HNPCC Oncogenes : - RAS proto- oncogenes ( chr 12) - responsible for aberrant crypt formation and adenomatous polyps

59. Adenoma carcinoma sequence Fearon -Vogelstein Adenoma-carcinoma sequence in sporadic and hereditary colorectal cancer.

60. Pathology: (Gross variants) Annular Tubular Ulcer Cauliflower Annular – obstructive symptoms Others - bleeding

61. Histological variants Adenocarcinoma - Mucinous adenocarcinoma - Signet ring adenocarcinoma - Spindle cell adenocarcinoma - Undifferentiated adenocarcinoma Medullary Micropapillary Serrated Cibriform Sarcoma Adenocarcinoma Mucinous Spindle cell

62. Clinical features Right colon: Melena Fatigue Anemia Abd Pain in advanced cases Obstruction (less common) Left colon: Altered bowel habits ( ↑ constipation) Sigmoid cancers mimic diverticulitis ( a/w pain and fever) Hematochezia Based on Anatomical location

63. Clinical features contd.. Involvement of Adjacent Structures Hydroureteronephrosis Duodenal obstruction Colo-vesical fistula Other symptoms Cachexia Ascites Anorexia

64. Investigations: Colonoscopy Double contrast barium enema CECT/MRI Virtual colonoscopy / CT colonography PET imaging

65. Investigation contd.. Others Include: Tumor markers – CEA Chest radiography Complete blood picture Determination of tumor genes (for RAS and BRAF ) Determination of tumor MMR or MSI status LFT and RFT

66. Colonoscopy: Gold standard Direct visualisation Biopsy can be taken Synchronous lesions or other polyps can be looked for Tattooing of lesions for surgery

67. DCBE Double contrast barium enema : Advantages- Done without sedation Very low risk Identifies lesions in the entire colon Accurately visualizes strictured areas Disadvantages: Radiation Unable to take biopsy hence subsequent colonoscopy is required Apple core sign

68. Radiograph of barium enema demonstrating a polypoid carcinoma arising in the cecum

69. Cect Relation and extent of disease Involvement of adjacent structures Lymphnode involvement Metastasis Secondary complications can be noted - Obstruction - Intusussception - Fistulae - Perforation

70. Descending colon cancer Liver metastasis

71. Ct vs mri MRI is superior in local staging of disease Both have similar sensitivity in nodal and distant spread CT is superior in detecting small pulmonary metastasis Small hepatic metastases MRI is excellent

72. Virtual colonoscopy When colonoscopy cannot be done Virtual Colonoscopy image showing an endoluminal 3D view

73. Virtual colonoscopy 3D luminogram showing the cecal wall retracted by the mass, acting as a lead point or an apex of the intussusceptum (arrow). Surgical image showing the invaginated ileum being pushed by the mass into the colon.

74. Pet: Equivocal to CT/MRI Liver mets Colon ca

75. Tnm classification T staging TX -Primary tumor cannot be assessed T0 - No evidence of primary tumor Tis -Carcinoma in situ—intraepithelial or invasion of lamina propria T1 - Submucosa T2 - Muscularis propria T3 - Muscularis propria into Pericolorectal tissues T4a - Tumor penetrates to the surface of the visceral peritoneum T4b - Tumor directly invades or is adherent to other organs or structures

76. TNM N staging NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in one to three regional lymph nodes N1a one regional lymph node N1b two or three regional lymph nodes N1c Tumor deposit(s) in the subserosa , mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis N2 Metastasis in four or more regional lymph nodes N2a four to six regional lymph nodes N2b seven or more regional lymph nodes

77. tnm Distant Metastasis (M): M0 - No distant metastasis M1 - Distant metastasis M1a - Metastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node) M1b - Metastases in more than one organ/site or the peritoneum

78. Histological grade (G) GX - Grade cannot be assessed G1 - Well differentiated G2 - Moderately differentiated G3 - Poorly differentiated G4 - Undifferentiated

79. Staging: Stage 0

80. Stage i

81. Stage ii

82. Stage iiia

83. Stage iiib

84. Stage iiic

85. Stage iv

86. treatment Management of malignant polyp: Endoscopic polypectomy Indications of surgery after polypectomy : Polyp specimen is fragmented Margins cannot be assessed Unfavorable histology - grade 3-4 - lymphovascular invasion - positive margins

87. Pathologic stage Following parameter should be reported: Grade Depth of penetration Number of Lymphnodes evaluated and number positive Status of proximal, distal, radial and mesentaric margins Lymphovascular invasion (LVI) Perineural invasion (PNI) Tumor deposits

88. Mx of invasive non metastatic cancer Surgery is the main stay of treatment Principles: -Removal of Primary with adequate margins -Minimum resection margin 5cm -Regional Lymphadenectomy -Restoration of continuity of bowel Extent of resection depends on - lymphatic drainage - vascular supply - Involvement of adjacent organs Circumferential resection margin

89. Mesenteric margin in portion of colon completely encased by peritoneum (dotted line) Circumferential margin (dotted line) in portion of colon incompletely encased by peritoneum

90. Surgical resections based on location of tumor Location: Caecum and Ascending colon Surgery : Right hemicolectomy Vessels ligated : - Ileocolic artery - Rt Colic artery - Rt branch of Middle colic artery Length of bowel: - terminal 6 cm of ileum, right colon and proximal transverse colon

91. Resections contd … Location: Hepatic Flexure Surgery : Extended Right hemicolectomy Vessels ligated : - Ileocolic artery - Rt Colic artery - Middle colic artery Length of bowel: - terminal 6 cm of ileum, right colon and proximal 2/3 rd of transverse colon

92. Resections contd … Location: Transverse colon Surgery : Extended Right hemicolectomy Vessels ligated : - Ileocolic artery - Rt Colic artery - Middle colic artery Length of bowel: - terminal ileum to descending colon (left of splenic flexure)

93. Resections contd … Location: Splenic flexure Surgery : Extended left hemicolectomy Vessels ligated : - Left Colic artery - Left branch of Middle colic artery Length of bowel: - mid transverse and descending colon

94. Resections contd … Location: Descending colon Surgery : Left hemicolectomy Vessels ligated : - Left Colic artery - Sigmoid vessels Length of bowel: - distal 1/3rd transverse colon , descending colon & part of sigmoid colon

95. Resections contd … Location: Sigmoid colon Surgery : Rectosigmoid resection Vessels ligated : - IMA after origin of Left Colic artery - Superior hemorroidal vessels Length of bowel: - descending colon to rectum

96. Lymphadenectomy Nodes at origin of feeding vessels should be examined Suspicious node outside the field of resection should be removed and examined Minimum nodes removed – 12 Positive nodes left behind indicated R2 resection Complete mesocolic excision (CME) along with central vascular ligation – better DFS (Disease Free Survival) Number of negative lymphnodes is an independent prognostic factor for stage IIIB and IIIC patients

97. Lymphadenectomy contd.. Examine lymphnodes for IHC and Micrometastasis Clumps of tumor cells - <0.2mm – Isolated tumor cells (pN0) - >0.2mm or 10-20 tumor cluster cells - Micrometastasis

98. MINIMALLY INVASIVE APPROACH Considered in: Experienced surgeon No locally advanced disease Not indicated in Intestinal obstruction Perforation Consider preoperative marking of lesions

99. Obstructing colon cancers: Usually seen in Left colon cancers Rx – - Emergency exploration - Resection of tumor segment with adequate margins - Primary anastomosis is not preferred -End colostomy with distal stump closure( Hartmanns procedure ) or Mucus fistula - if primary anastomosis is considered, then on table lavage through appendix or ileum should be done (in hemodynamically stable patients only)

100. Hartmanns operation:

101. Mucus fistula

102. Obstructing colon cancers…. SEMS: Recently SEMS have been used as a bridge to surgery Hence elective surgery with primary anastomosis Insertion of SEMS using a guide wire

103. Adjuvant therapy Not indicated in: Stage I Patients with MSI-High Stage IIa Indicated in Stage IIb , IIc (Excluding MSI- high) Stage III LVI and PNI Bowel obstruction Localised perforation Closed, indeterminate or positvie margins Inadequately sampled nodes(<12)

104. Timing of adjuvant therapy As soon as patient is fit Each 4 week delay in Chemotherapy - 14% decrease in overall survival Regimens include: FOLFOX( Leucovorin calcium, 5 Fluorouracil, Oxaliplatin ) CapeOX ( Capecitabine / oxaliplatin ) Bolus 5FU/LV/ Oxaliplatin (FLOX)

105. Perioperative Chemoradiation : Neoadjuvant or Adjuvant radiation therapy delivered concurrently with 5 FU based chemotherapy Indicated in: - T4 tumors penetrating to fixed structures - Recurrent disease - locally unresectable or inoperable tumors

106. Management of metastatic disease Mc site – Liver > Lungs 20-30% - Synchronous liver mets Standard treatment – Resection If resection is not feasible: Image guided ablation or Sterotactic Body Radiation Therapy(SBRT) HAI(Hepatic Aretrial Infusion) Radioembolisation TACE ( Transcatheter Arterial Chemo- Embolisation ) RFA, Cryoablation , Microwave ablation Percutaneous ethanol injection

107. Management of metastatic disease Surgical re-evaluation is done in every 2 months to check for resectability Neoadjuvant or Adjuvant therapy For 6 months Biologics are not recommended in the peri -operative period

108. Management of metastatic disease Peritoneal carcinomatosis : Seen in 17-20% of cases Role of cytoreductive surgery + HIPEC still debatable Systemic therapy: 5FU, LV, Capecitabine , Irinotecan , Oxaliplatin Bevacizumab , Cetuximab , Panitumumab , Ramucirumab Regorafenib , Pembrolizumab , Nivolumab etc

109. Management of metastatic disease Cetuximab and panitumumab are effective only on tumors that do not have a mutation of the KRAS gene . Bevacizumab – VEGF inhibitor Cetuximab – EGFR inhibitor

110. Role of genetic testing Stage IV disease – look for KRAS NRAS and BRAF mutations To take decision on biologics to be used Prognostication Personal history of colon cancer: Look for MSI or MMR testing Presence of BRAF V600E in absence of MLH1 precludes Lynch syndrome

111. Surveillance Stage I: Colonoscopy at 1 year and repeat at 3years and then every 5 years If advanced adenoma is detected then repeat every year Stage II / III: History and physical examination every 3-6 months for 2 years, then every 6 months for 5 years CEA 3-6 monthly for 2 years, f/b 6 monthly for 5 years Colonoscopy 1year, 3 rd year f/b for every 5 years More frequent colonoscopies if age < 50 years

112. Surveillance Stage II / III: contd … Chest, abdomen and pelvic CT 6-12 monthly for upto 5 years CEA monitoring upto 5 years Stage IV: CT chest, abdomen and pelvis; CEA levels every 3-6 months for first 2 years after adjuvant therapy And 6-12 monthly for upto total of 5 years

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