Transcript HNPCC Colonoscopy and Surgery

BOWEL CANCER AND SCREENING IN
LYNCH SYNDROME
Nick Beck
Colorectal surgery, Southampton
BOWEL CANCER AND SCREENING IN LYNCH SYNDROME
How common is bowel cancer?
(How common is Lynch syndrome?)
Screening guidelines for colonoscopy in Lynch syndrome
Colonoscopy & Other methods of screening (again)
Treatment of bowel cancer
Bowel cancer is a common cancer
About 1 in 20 (5%) of the population will develop colorectal cancer
How common is bowel cancer in Lynch Syndrome/HNPCC?
• There is a wide variation in cancer risk between families.
• The risk is influenced by environmental and genetic factors
• Carriers of a MMR gene mutation have a 25-70% risk of developing
CRC
Lynch syndrome is probably underdiagnosed
Identification is important as individuals can benefit from lifesaving
cancer surveillance
Improving the identification of Lynch
Syndrome
• Increasing awareness (in population)
• Promoting the taking of a family history by doctors
• Via patients diagnosed with bowel cancer or endometrial cancer
Young age onset
Multiple tumours
Affected family members
Molecular analysis of the tumour
(Bethesda criteria – complex)
• Systematic testing of all pts with CRC for loss of MMR – Identified about
3% of pts had LS.
Why do we screen the bowel of Lynch
Syndrome patients ?
• Because the risk of bowel cancer is high in HNPCC patients
• Because we can detect polyps before they become cancers
• Because we can detect bowel cancer at an earlier stage
• Because bowel cancer can be completely cured if detected early
enough.
Screening for bowel cancer in Lynch Syndrome
Is it effective?
YES
• Colorectal surveillance is the only surveillance protocol in LS proved
to be effective
• Regular colonoscopy – leads to a reduction in CRC related mortality
• Regular colonoscopy – significant reduction in overall mortality
What is the optimal interval between examinations?
• Ongoing discussion
• 3-year interval proved to be effective
(Jarvinen HJ, Mecklin JP, Sistonen P. Screening reduces colorectal cancer rate in families with
hereditary nonpolyposis colorectal cancer. Gastroenterology 1995;108:1405–11).
But probably colonoscopy should be more frequent:
• it is known that cancer can be found/develop after a ‘negative’
screening examination – ‘interval cancer’.
• Although most of these cancers are early (stage I and II) some are
more advanced (5-20%).
Number of studies looking at effectiveness of screening with different
intervals (1, 1-2, 2 yearly) but they have not compared the intervals.
• Most interval cancers were right sided (57-62%)
• Most int cancers were in individuals over 40 (but not all)
• Mortality is associated with a lack of participation in a screening
programme.
• Perhaps the risk is less for pts with an MSH6 mutation (but not
significant)
so
• Colonoscopy screening in LS patients reduces the chance of dying
from CRC
• Screening should be at least 3 yearly but probably 1-2 yearly.
• It’s very important that the colonoscopy is complete (to the caecum)
• It’s very important that people turn up for their screening
• The British Society of Gastroenterologists recommends colonoscopy at
least every 2 years from the age of 25.
• Recommendations for screening in HNPCC (USA) © 2014 by American
Society of Clinical Oncology - Colonoscopy every 1 to 2 years, starting at
age 20 to 25 or 5 years before the youngest case in the family. No upper
limit is established.
Dedicated family history screening lists
•
•
•
•
•
•
Team familiar with Lynch syndrome
One colonoscopist, one colorectal nurse specialist (Sue),
Genetics input
Consultant delivered
High completion rate
Aim for high level of participation (try to contact non-attenders) and rearrange date.
(high participation, high completion rate, comfortable examination, ‘One
stop’ service)
colonoscope
Insert scope
Identify polyps
view
Remove polyps
Are there any alternatives to screening with
colonoscopy?
• CT colonography (‘virtual colonoscopy’)
• MRI colon
possible (Radiation dose)
perhaps
•
•
•
•
•
not sensitive enough
better for small bowel
not good enough
BCSP but not for HNPCC
possible in the future
‘CT colon’ or ‘CT abdo/Pelvis’
Capsule endoscopy
USS
Faecal Occult Blood (FOB)
Molecular markers / stool testing
CT colonography / CT colonoscopy / Virtual colonoscopy.
• Well tolerated
• Good at picking up cancer and large polyps
• Not as sensitive for smaller polyps
• Not therapeutic
• Radiation dose
Friday August 15 2014
BBC News reports on a sharp rise in the number of CT scans being performed, exposing people to the potential health risks of
radiation. Patients receive a dose of radiation during a CT scan
CT scans can be vital for helping make decisions about treatment
However, it is not possible to calculate the cancer risk due to exposure to CT scans because there is a lack of data.
• Radiation is meaured a variety of ways. One of the units of measurement is Sieverts (Sv). This meaures the
effect of radiation on the body. We are naturally exposed to radiation from many different sources such as
the earth, atmosphere and space. Background radiation at sea level: 3 mSv per year
• Denver residents get: 6 mSv per year
• Cross country flight: 0.02 mSv
• X ray Chest: 0.06 mSv
• CT Head: 3 mSv
• CT Chest: 5 mSv (equivalent to 100 chest xrays)
• CT Abdomen: 5-10 mSv
(Some experts believe that above 50 mSv there is a slight increase in risk of cancer).
MRI colonography
• No radiation
• But not therapeutic
• And not better tolerated than colonoscopy
• Beth Israel Deaconess Medical Center, compared the efficacy of MRC using air as an intraluminal
contrast agent with optical colonoscopy in 46 patients. MRC identified lesions greater than 10 mm
with 100% sensitivity and specificity. For intermediate and small lesions, sensitivity dropped to
50% and 15%, respectively, while specificity remained high.
• While these results indicate that the technology is effective, other results revealed that patients
are just as resistant to MRC as they are to optical colonoscopy. Keeling found that 35% preferred
MRC over optical colonoscopy, 33% preferred colonoscopy to MRC, and 32% had no preference.
Patients reported slightly more discomfort with MRC but more embarrassment with optical
colonoscopy
Treatment of colorectal cancer
• Surgery is the primary treatment.
• Debate about the extent of surgery required
• Radiotherapy (?)
• Chemotherapy (?)
• Bowel cancer is often curable
Surgery
Surgery for HNPCC patients
• In general outcomes for surgery for colorectal cancer patients are
very good
• Many patients are cured
• Many cases can be performed with laparoscopic surgery (keyhole)
• Mortality rates are low
• But it’s not clear how (or if) surgery should change if the CRC
develops in a HNPCC patient.
How much of the colon should be removed?
Segmental resections
Segmental vs radical resections
Surgical treatment for colorectal cancer
After standard treatment of a CRC
-The risk of developing a second cancer is 16% at 10 years (despite
close surveillance)
Reduction of risk with further resection
vs
Risk of further resection
Reduction of quality of life
with further resection
• Functional outcome worse after extensive surgery but the quality of
life was similar!
Choice of operation?
•
•
•
•
Balance of risks
Not clear if there is a need to be more radical.
Sometimes there are multiple cancers – more radical
Sometimes large polyps / more polyps than usual – more radical
• Discuss with Genetics team
• Discuss with your surgeon
• Surgical outcomes are very good
• After surgery - Continue colonoscopy screening
Other additional treatments?
• Radiotherapy (for rectal cancer)
• Chemotherapy (difficult)
colorectal cancers characterised by deficient MMR are distinct
from tumours that arise from chromosomal instability
MSI – H have a better prognosis but
MSI – H don’t seem to benefit from Adjuvant flurouracil (FU)
based chemotherapy
Discuss with oncology
Any questions?
• Or during tea/coffee break?
Risk of cancer according to carrier:
• MLH1-mutation carriers tend to develop CRC at younger ages
• MSH2 carriers seem to be at higher risk for extracolonic cancers
• Women with MSH6 mutations may have a greater lifetime risk of
endometrial cancer than CRC.
• PMS2 carriers have a lower risk for CRC and endometrial cancer (15%
to 20%) compared with carriers of other MMR gene
© 2014 by American Society of Clinical Oncology
Hereditary Colorectal Cancer Syndromes: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the Familial Risk–Colorectal Cancer: European Society for Medical Oncology
Clinical Practice Guidelines
Elena M. Stoffel, Pamela B. Mangu, Stephen B. Gruber, Stanley R. Hamilton, Matthew F. Kalady, Michelle Wan Yee Lau, Karen H. Lu, Nancy Roach and Paul J. Limburg
Lifetime risks of other cancers in HNPCC:
• Endometrial cancer (lifetime risk, 30% to 60%) - surgical removal of the uterus
and ovaries has been shown to reduce incidence of endometrial and ovarian Ca.
• tumours of the urinary tract (lifetime risk, 5% to 12%)
• small intestine
• ovary (lifetime risk, 4% to 12%)
• stomach (lifetime risk, 8% to 10%)
• pancreas (lifetime risk, 4%)
• biliary tract
• brain
• skin