COLORECTAL CARCINOMA AND ITS MANAGEMENT.....

1. z

2. GASTRO INTESTINAL MALIGNANCIES
{ANAL CANAL CARCINOMA AND ITS
MANAGEMENT}
PRESENTED BY -
DR ABHISHEK JOHARI
{J.R.2 GENERAL
SURGERY}
MODERATOR –
DR SMITA CHAUHAN SINGH
{DNB GENERAL SURGERY}

3. What this presentation covers INTRODUCTION
 EPIDEMIOLOGY
 ETIOLOGY
 RISK FACTORS
 CARCINOGENESIS
 MORPHOLOGY/PATHOLOGY
 CLINICAL FEATURES
 CLASSIFICATION
 SCREENING
 DIAGNOSIS
 STAGING
 TREATMENT
 FOLLOW UP
 RECENT ADVANCES

5. ** Colorectal cancer (CRC) starts in the colon or rectum
**3rd most common form of cancer
**2nd leading cause of cancer deaths in US
**Mortality has declined over the past 20 years with
better screening, diagnosis and treatments
**Screening for/removing polyps early is the best way to
prevent and cure CRC

6. Colorectal CancerColorectal Cancer
Sporadic (average risk)
(65-85%)
Family History (10-30%)
Hereditary nonpolyposis
colorectal cancer (HNPCC)
(5%)
Familial adenomatous
polyposis (FAP) (1%)
Rare syndromes (<0.1%)

7. Adenocarcinoma
98% of all cancers in large intestine
 arise in adenomatous polyps, generally curable by
resection

9. Epidemiology
peak incidence: 60 to 70 years of age
< 20% cases before age of 50
adenomas – presumed precursor lesions for most
tumors
males affected ≈ 20% more often than females

10. Epidemiology
worldwide distribution
highest incidence rates in United States, Canada,
Australia, New Zealand, Denmark, Sweden, and other
developed countries

12. Etiology
genetic influences:
ulcerative colitis or polyposis syndrome
hereditary nonpolyposis colorectal cancer syndrome
(HNPCC, Lynch syndrome) germ-line mutations of→
DNA mismatch repair genes

13. Etiology
environmental influences:
dietary practices
 low fiber
 high carbohydrates
 high fat content
 decreased intake of (vitamins A, C, and E)

15. Colorectal Cancer Risk FactorsColorectal Cancer Risk Factors
Age
 90% in 50 yrs and older
Gender
 male predominance,
Race/Ethnicity
 African Americans in U.S.,
 Alaska Natives, some American Indian tribes, Ashkenazi Jews
Increased risk with:
Personal history of inflammatory bowel disease, adenomatous polyps, colon cancer,etc
**Lifetime risk for CRC increases for members in which index case is
young {<50 yrs}and relative is first degree.

16. Risk Factors - PolypsRisk Factors - Polyps
Different types
• Hyperplastic
Minimal cancer potential
• Adenomatous
Approximately 90% of colon and
rectal cancers arise from
adenomas

18. Normal to Adenoma to Carcinoma
Human colon carcinogenesis
progresses by the dysplasia/adenoma
to carcinoma pathway

19. Genetic Model of Colorectal CancerGenetic Model of Colorectal Cancer
Normal
Epithelium
Adenoma
Late
Adenoma
Late
Cancer
Early
Cancer
Dwell Time: Many decades 2-5 years 2-5 years
Mutation
APC K-ras p53
Bat-26 (HNPCC) Bat-26 (Sporadic)
Optimum phase
for early detection

20. Carcinogenesis
chromosome instability pathway

21. Carcinogenesis
mismatch repair (microsatellite instability) pathway

23. Morphology
begin as in situ lesions
tumors in the proximal colon: polypoid, exophytic
masses that extend along one wall of the cecum and
ascending colon

24. Morphology
in the distal colon: annular, encircling lesions that
produce “napkin-ring” constrictions of the bowel and
narrowing of the lumen
both forms of neoplasm eventually penetrate the
bowel wall and may appear as firm masses on the
serosal surface

26. Clinical Features
asymptomatic for years
symptoms develop insidiously
cecal and right colonic cancers:
fatigue
weakness
iron deficiency anemia
left-sided lesions:
occult bleeding
changes in bowel habit
crampy left lower quadrant discomfort
anemia in females may arise from gynecologic causes, but it is a
clinical maxim that iron deficiency anemia in an older man means
gastrointestinal cancer until proved otherwise

27. SYMPTOMS
RECTAL BLEEDING
LOWER RECT.
TENESMUS
ALT. OF BOWEL HABITS
UPPER.

31. Staging Rectal Cancer
Modified Dukes
staging..
A: Contained within the
bowel wall.
B: Penetrates the bowel
wall.
C: Metastasis to Lymph
nodes.
D:Metastasis to distant
organ.
TNM
Stage I: Confined to the
mucosa or contained with
bowel wall (T1, T2).
Stage II: penetrates the
bowel wall (T3, T4).
Stage III: Metastasis to
lymph nodes (N1, N2).
Stage IV: distant spread.

33. • Patients with a family history, a history of
adenomatous polyps, and a history of ulcerative
colitis should be considered for colonoscopic
surveillance.
• Faecal occult blood testing is the only
population screening modality that has been
shown to reduced colorectal cancer
mortality.

34. Benefits of ScreeningBenefits of Screening
Cancer Prevention
Removal of pre-cancerous polyps prevent cancer
Improved Survival

35. CRC Screening GuidelinesCRC Screening Guidelines
What Else is New?What Else is New?
Two new tests recommended:
Stool DNA (sDNA) and
Computerized tomographic colonography (CTC)-sometimes
referred to as virtual colonoscopy.

36. 2008 CRC Screening
GuidelinesGuidelines
Beginning at age 50, both men and women at average risk for developingBeginning at age 50, both men and women at average risk for developing
colorectal cancer should use one of the screening tests below:colorectal cancer should use one of the screening tests below:
Tests That Detect Adenomatous Polyps and CancerTests That Detect Adenomatous Polyps and Cancer
Flexible sigmoidoscopy (FSIG) every 5 years*, or
Colonoscopy every 10 years, or
Double contrast barium enema (DCBE) every 5 years*, or
CT colonography (CTC) every 5 years*
Tests That Primarily Detect CancerTests That Primarily Detect Cancer
Annual guaiac-based fecal occult blood test (gFOBT) with high test sensitivity for
cancer*, **, or
Annual fecal immunochemical test (FIT) with high test sensitivity for cancer*, **, or
Stool DNA test (sDNA), with high sensitivity for cancer*, interval uncertain
*Colonoscopy should be done if test results are positive.
**For gFOBT or FIT used as screening test, the take-home multiple sample method should be used.
gFOBT or FIT done during a digital rectal exam in the doctor’s office is not adequate for screening.

37. Stool DNA Test (sDNA)Stool DNA Test (sDNA)
• Rationale
• Fecal occult blood tests detect
blood in the stool – which is
intermittent and non-specific
• Colon cells are shed continuously
• Polyps and cancer cells contain
abnormal DNA
• look for abnormal DNA from
cells that are passed .

38. Stool DNAStool DNA
Limitations
 Misses some cancers
 Sensitivity for adenomas is low
 Technology (and test versions) are in transition
 Costly
 Not clear how to manage positive stool DNA test if colonoscopy is negative

39. CT ColonographyCT Colonography
Rationale
 detailed evaluation of the entire colon
 high level of sensitivity for cancer and large polyps
 Minimally invasive (rectal tube for air insufflation)
 No sedation required

40. CT Colonography (CTC)CT Colonography (CTC)
CTC Image Optical Colonoscopy

41. CT ColonographyCT Colonography
3-D view2-D view
PolypPolyp

42. CTC – Extra-Colonic FindingsCTC – Extra-Colonic Findings
Asymptomatic cancers outside of colon and
rectum
Aortic aneurysms
Renal and gall bladder calculi

43. CT ColonographyCT Colonography
Limitations
Requires full bowel prep
Colonoscopy is required if abnormalities detected, sometimes necessitating
a second bowel prep
Steep learning curve for radiologists
Limited availability

45. • Colonoscopy is the gold standard
investigation.
• Barium enema underdiagnose cancer
in the sigmoid colon and overdiagnose
in the caecum.
• Double contrast barium enema should
be supplemented
by flexible sigmoidoscopy.

46. • All patients should have a contrast enhanced
computed tomography of the liver and chest to
look for metastatic disease.
• MRI is the most accurate means of
preoperative staging for rectal cancer.
• Endoluminal ultrasound is particularly useful
in distinguishing
benign rectal tumours from early cancer.

48. Endorectal Ultrasound
Accurate evaluation of depth of invasion
Good assessment of lymph nodal disease
especially if positive
Critical for pre-operative and pre-RT staging
Important tool in post-operative and post-RT f/u

49. MRI
HIGH RESOLUTION THIN SLICE (<1mm)
DEPTH OF EXTRAMURAL SPREAD
ACCURATELY IDENTIFIED (AIDS
CIRCUMFERENTIAL RESECTION
MARGIN)

50. MRI
DETECTS EXTRAMURAL VENOUS
INVASION (EMVI)
 POOR PROGNOSIS WITHOUT
CH/RT IF EMVI PRESENT

53. • Surgery is the only potentially curative treatment for
colorectal cancer.
• Anastomotic dehiscence rates should be less that 5% in
colonic surgery.
• The outcome of rectal cancer surgery is highly
dependent
on the quality of the surgery, which is based on
mesorectal
excision.
• Anastomotic dehiscence rates after total mesorectal
excision tend to be high, and consideration should be

54. Basic Surgical Approach
Level of Tumor
Upper rectal
Mid rectal
Lower rectal
Procedure
Anterior Resection
Low Anterior Resection
Local Excision
LAR with TME
APR

55. Historical vignettes
1826: Lisfranc 1st report of local excision
1979: Heald introduces TME Total Mesorectal Excision
1984: Buess introduces TEM Transanal Endoscopic Microsurgery

56. A-B right hemicolectomy
A-C extd right hemicolectomy
B-C transverse colectomy
C-E left hemicolectomy
D-E sigmoid colectomy
D-F anterior resection
D-G (ultra) low anterior resection
D-H abdomino-perineal resection
A-D subtotal colectomy
A-E total colectomy
A-H total procto-colectomy
A
B C
D
E
F
G
H
© CCrISP Australasia 3rd Edition
Colorectal Major Resections

57. Rectal Ca Local excision -
Recommended criteria:
<10 cm from anal verge
Tumour < 4cm and <40% of circumference
Favourable T1 stage
 Well- moderate differentiation
 No lymphovascular or perineural invasion
 Non-mucinous tumours
No nodal disease

58. Rectal Ca Local excision – Transanal approaches
Transanal excision
Full thickness excision with 1cm margin
Rectal defect closed transversely
Local recurrence high

59. Rectal Ca Local excision – Transanal approaches
Transanal Endoscopic Microsurgery (TEM)
Developed for lesions out of reach from transanal approach
Can be used for benign lesions above the peritoneal reflection

60. Rectal Ca Local excision - Ablative
procedures
Electrocoagulation
Used as palliative & curative Rx
Disadv: no tissue spec, 1/3 conversion to radical surgery, 20%
secondary haemorrhage
Poor outcomes
Endocavitatory radiation
Direct contact radiation 10-12000 cGy
Useful in palliative setting
In select pts 5yr survival & local control of 76-90%

61. Radical excision-Total Mesorectal Excision(TME)
Introduced by RJ Heald in 1979
Use of sharp dissection under vision to mobilize the rectum
rather than the conventional blunt finger dissection
Local recurrence:
Conventional surgery: 11.7 - 37.4%
TME surgery: 1.6 - 17.8%
Higher leaks rates reported possibly due to:
Devascularisation of distal rectal stump
Lower anastamosis
Other factors: stomas, drains

64. Reconstruction of Neorectum
 Straight end to end
 (Anterior resection syndrome)
 Colonic J Pouch
 Increases volume of neorectum
 Size is critical to functional outcome, recommend 5-8 cm
 Sigmoid colon should not be used
 lower anastamotic leaks compared to end-to-end anastamosis
 Coloplasty
 New technique introduced in 1999
 Better in narrow pelvis and limited length of colon
 Long incision closed transversely

65. Reconstruction of Neorectum
Hand sewn sutured anastamosis
1982: Parks and Percy performed the coloanal sutured anastamosis
‘Pulled through’ coloanal anastamosis (Turnbull & Cuthbertson)
Stapled anastamosis
Circular stapled technique
Double staple technique
 For low and coloanal anastamosis

66. Abdominoperineal Resection
Described by Sir Ernest Miles 1908
1-2 surgeons
TME rectal dissection
Anus sutured closed
Wide perineal dissection, starting from posterior to lateral then anterior
Anterior dissection can proceed cranio-caudal or vice versa
Drain the pelvic space
Reduced rates of APR
 Coloanal anastamosis
 Acceptance of smaller margins
 Downsizing by chemoradiotherapy

68. Sacro-coccygectomy with APR

69. Laparoscopic Resection

70. Anastomotic leak
Inraabdominal abscess,
stoma retraction,
haemorrhage,
Dvt,
wound infection,

72. • stage C colorectal cancer -5-fluorouracil based
adjuvant chemotherapy.
• Preoperative radiotherapy preferable to
postoperative treatment.
• Preoperative radiotherapy reduces the risk of
local recurrence of rectal cancer,

73. USE OF CH/RT
(NEOADJUVANT/ADJUVANT)
PTS WITH POOR HISTOLOGY
PTS WITH EXTRA MURAL SPREAD (MRI)
PTS WITH INVOLVED NODES (ERUS)
PTS WITH EMVI (MRI)

74. Agent FDA approval status
Bevacizumab 2004
(Anti-VEGF Ab)
Cetuximab 2004
(Anti-EGFR Ab)
Panitumumab 2006
(Anti-EGFR Ab)

75. The Rational for Neo-adjuvant therapy
Early lesions --T1 and T2 -- carry a 10% to 25 %
chance of lymph nodal disease.
Down staging of T3 tumors aid sphincter savage.
Multi-modality approach can cover for metastatic
lymph node disease.
Radical resection can be very morbid.

76. Advantages of Neoadjuvant Therapy
Sphincter preservation
Decreased or delayed local recurrence
Increase survival
Certainty of treatment
Improved symptoms

77. Disadvantages
Treating tumors that don’t need therapy
Delaying surgery
Increase morbidity
sphincter dysfunction
sexual dysfunction
urinary dysfunction
Irradiated bowel

78. Contra-indications to neo-adjuvant
therapy
Upper rectal cancers
Early T1 lesions
Obstruction
Known stage IV disease
Patient can not tolerate therapy.

80. • Patients with isolated liver metastases should be
considered for liver resection.
• Systemic chemotherapy can prolong survival, but
is palliative.
• Although chemotherapy is still largely based on
5-fluorouracil, newer agents, notably capecitabine
and irinotecan, are showing significant promise.

82. Follow up is carried out for:
• Early detection of metastases.
• Detection of metachronous polyps or cancers.
• Psychological support.

83. A regimen for follow-up
Clinic visits q 6 months
CEA q 6 months
Rigid Sigmoidoscopy q 6 months
Rectal Ultrasound q 6 months
Colonoscopy at 1 year
CT and PET as clinically indicated.

84. Rising CEA and Recurrent Disease
Rising CEA represents recurrent disease which
may be local, distant, or both.

86. MOLECULAR BIOLOGY
 DNA CHIP TECH. – DNA SEQUENCE
CHECKED
-- APC GENE – FAP
-- MISMATCH REPAIR GENES –
HNPCC
SUCH PTS.(5%) PUT ON A
SURVEILLANCE PROG. --PROPHYLACTIC
SURGERY

87. MOLECULAR BIOLOGY
DNA SEQUENCE OF MICROSATELLITE
INSTABILITY
-- GOOD RESPONSE WITH 5 FU CHEMO.
P21 MARKER POSITIVE – RADIOSENSITIVE

88. MOLECULAR BIOLOGY
P53 PROTEIN MUTANT EXPRESSED --
RADIORESISTANT
KRAS, DCC, AND P53 -- IF +ve – POOR PROGNOSIS
MICROSATELLITE INSTABILITY OR LOW Cox2
EXPRESSION & P21 MARKER – IF +ve – GOOD
PROGNOSIS

89. THANK YOU