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Molly M. Cone, MD
Assistant Professor of Surgery
Vanderbilt Medical Center


November 14, 2014

No disclosures
o Review screening options and recommendations for colorectal
cancer
o Understand criteria for referral for genetic testing in patients with
colon cancer
o Learn about current surgical options for patients with colorectal
cancer

Epidemiology:
o In 2014:
• 96,830 colon cancer diagnosed
• 40,000 rectal cancer diagnosed
o Lifetime risk 1/20 (5%)
o 3rd leading cause of cancer related deaths in US
• 50,310 expected to die of CRC in the US this year
o Worldwide- responsible for over 650,000 deaths annually (WHO)
•
•
Both incidence and
deaths from colon and
rectal cancer have been
declining
Except in those <50 yrs


Why screen?
Cost effectivelarge number of incident cases, long duration of disease
manifestation, and high mortality
o simple methods for detection and reasonable treatment options
o

Saves liveso
screening for CRC not only detects cancer earlier, but also allows
the clinician to intervene and change the course of the disease.
x
DCC 18q
8-10 years
x

Problems with screeningo multiple methods lead to considerable confusion regarding which
method is best and the optimal timing .
o confusion causes physicians to reduce the importance paid to CRC
screening

This reduces the number of patients who ultimately get
screened

Physician Recommendation
o Patients indicate as the single most important factor in deciding to
undergo screening

From National Cancer Institute:
o >42% of patients were unaware of potential screening options
o only 35% of respondents were aware that colonoscopy could
actually detect CRC

Fecal Occult Blood Test (FOBT)
o only screening test which has shown efficacy in prospective
randomized controlled trials

Fecal Immunochemical based stool Tests (FIT)
o more specific for hemoglobin, this test avoids some of the false
positive results of FOBT

DNA stool Assays (sDNA)
o Cells shed from the polyp/cancer contain DNA mutations that can
be used as a biological marker for cancer detection

Serum Markers
o Two most studied- CEA, CA 19-9
• CEA used as biologic marker for progression of cancer, but only 30%
sensitivity rate for detection
• CA 19-9 not been found useful

Barium Enema (double contrast)
o Good sensitivity for cancer- 85-97%, questionable for polyps 32-60%
depending on size

CT Colonography
o Must undergo complete bowel prep and have air/CO2 insufflated
though a rectal catheter to distend the entire colon
o May use barium per rectum to “tag” any residual stool in the colon

Drawbacks to CT colonography
o nontherapetic modality, and positive findings require intervention
o No standardized protocol
o Difficult to detect low rectal lesions
o Pt still takes the prep

Colonoscopy
o considered the gold standard test for detection
o considered to have the highest sensitivity and specificity
o there are NO randomized controlled trials
 Multiple
societies/ organizations have
recommendations, all that differ slightly
 Most agree that for average risk, screening
should begin at age 50
 Screening ends by age 85, with a range of 7585
Method
Interval
Society
Fecal Occult Blood Testing or FIT
Yearly
USPSTF, ASGE, USMSTF
Fecal DNA
Unspecified
USMSTF
Tests that detect
Double Contrast Barium Enema
Every 5 years
USMSTF
Cancer and Polyps
CT Colonography
Every 5 years
USMSTF
Flexible Sigmoidoscopy
Every 5 years
USPSTF, ASGE, USMSTF
Flexible Colonoscopy
Every 10 years
USPSTF, ASGE, USMSTF
Tests that detect Cancer
United States Preventive Services Task Force (USPSTF), American Society of Gastrointestinal
Endoscopy (ASGE) , U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF)
Environmental
Factors
Genetic
Susceptibility
Cancer
Age/Time

Diet:
o High fat
o Low fiber
o Red meat
o Low calcium
o Obesity
o Smoking
o Physical activity
Sporadic (65-85%)
Familial
(10-30%)
Rare CRC
Syndromes (<0.1%)
FAP (1%)
HNPCC (2-5%)


Hereditary Non-Polyposis Colon Cancer
2-5% of all colorectal cancers
o Lynch 1
• Colorectal cancers only
o Lynch 2
• Colorectal cancers
• Other cancers (Endometrial, ovarian, pancreatic, gastric, transitional
cell of kidney/ureter)
•
Most common inherited colon cancer syndrome

Amsterdam II
criteria
• 3 – 2 – 1 Rule
– 3- family members with CRC or
HNPCC associated CA
(2 first degree)
– 2- generations involved
– 1- family member < 50 years

Bethesda guidelines:
o Meet Amsterdam criteria
o Individuals with 2 HNPCC-related cancer
o Individual with CRC and
• 1st degree relative with HNPCC-related CA <45yo
or
• 1st degree relative with adenoma < 40yo
o Individual with R-side CRC with undiff pattern <45yo
o Individual with CRC or endometrial CA <45yo
o Individual with signet cell CRC <45yo
o Individual with adenoma <45yo

Genetic testing should be considered when
o Individual meets Amsterdam criteria
o Individual meets Bethesda guidelines
o Tumor is MSI +

Pre-operative workup
o Colonoscopy- evaluate for other polyps/cancers
o CEA level
o CT scan of chest/abd/pelvis

Surgical principles
o Exploration- either lap or via open techniques
• Evaluate peritoneum, adjacent organs, and liver
o Resection
• Removal of primary lesion with “adequate” margins
• Removal of the zone of lymphatic drainage- defined by arterial blood
supply, resected at or near origin
Laparoscopic vs. open?
 Literature- Laparoscopic colectomy is equivalent cancer
related survival to open colectomy
 Benefits of laparoscopic methods for postoperative recovery

Differs from colon cancer
o Pelvic anatomy
o Radiation therapy
o Surgical treatment options

Pre-op work-up
o Very important, as stage effects order/components of treatment
•
•
•
•
•
Colonoscopy- evaluate for other polyps/cancers
CEA level
CT scan of chest/abd/pelvis
Endorectal ultrasound or MRI
Physical exam/flex sig

DRE informationo Location
o Position
o Size
o Fixed vs. mobile

Endorectal ultrasound/MRI:
o the most important pre-operative component
• ERUS- 67-95% sensitivity for T stage
• MRI (with EndoCoil) 60-95% sensitivity
• Both modalities are less sensitive for N stage
• Determine the need for Neoadjuvant
5FU/Radiation
• Stage II and III (T3, T4, and/or N+)

Before the 1970’s rectal cancer was treated with surgery
alone
o 1975 trial comparing surgery with chemo, XRT, or both
•
•
•
•
Surgery only- 55% recurrence
46% with chemotherapy,
48% with radiation therapy
33% with combined modality
o NIH Consensus Statement 1990
• Stage II and III rectal adenocarcinoma should be treated with
adjuvant chemoradiotherapy

At the same time- specifically in the 1990s, there became a
realization that not all surgery was being performed equally
o “Total mesorectal excision”

Distal Mural Resection Margin
o 1-2 cm
o Tumors do not spread longitudinally
in wall of rectum

Radial Margin
o Critical to ensure complete tumor removal
o Pathologists must measure and report

Mesorectal Margin
A review of 51
surgical series
showed that TME
reduced the median
local recurrence rate
from 18.5 to 7.1%.
 German
rectal cancer trial update 2004
n
Local pelvic failure
12%
Survival
Anastomotic leak
Toxicity (acute)
Toxicity (late)
Preop XRT
405
6%
Postop XRT
392
No difference
No difference
Lower
Higher
Lower
Higher
•Shrink tumor prior to removal
•Downsizing
•Downstaging
•Sterilize margins prior to pelvic
dissection
•More effective than postop XRT
• oxygenated field
•Better functional result
•Radiate only one side of
anastomosis
•More patients complete
treatment
course
 Prospective,
Randomized, n=1748
 Pre-Op XRT vs. surgery alone (TME)
 Local
pelvic failure (recurrence)
XRT + Surgery
Surgery
2.4%
8.3%
5.8%
11.4%
2 yrs
5 yrs

Laparoscopic vs. open resection for rectal cancer

1 major trial, 1 underway

Prospective, randomized, experienced surgeons

Disease free survival and local control (3 years)
• n=794 overall
• n=242 rectal
o No difference between laparoscopic and open
o Local failure
• Anterior resection
• APR
open
7%
21%
lap
8%
15%
________________________________________________

ACASOG Z6051 Trial
o American College of Surgeons Oncology Group
o 650 pts, randomized, multi-center trial of open vs. HALS resection for rectal
cancer

Prosgood visualization
o precise movements
o better ergonomics
o

Conso hard to move from one quadrant to another
o costly
o lack of stapler/vessel sealing device

Unless directly invaded by
tumor, skeletal muscle is not
at risk for tumor
implantation.

Therefore, there is no reason
to excise the anus or
levators…
… if it will not improve
oncologic outcome.
 Appropriate
if tumor
invades anal
sphincter
or levator ani

Coloanal anastomosis

Same dissection, but instead of
removal of the anus, the colon is
hand sewn to the anal mucosa

Transanal Endoscopic Micro Surgery
o Can do full thickness excision of rectal wall
o Ideal for
•
•
•
•
Unresectable adenomas
Carcinoid tumors
T1 rectal cancer
T2 rectal cancer?

In the past 3 decades significant changes in the diagnosis
and treatment of colon and rectal cancer has resulted in:
o Decrease in incidence
o Decrease in mortality
o Less invasive procedures with shorter hospital stay