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Dr Alasdair PatrickGastroenterologist and
General Physician
Middlemore Hospital
Auckland
8:15 - 9:10 WS #194: Bowel Cancer
9:20 - 10:15 WS #206: Bowel Cancer (Repeated)
Dr Ben LawrenceMedical Oncologist
Auckland Hospital
Senior Clinical Research
Fellow
University of Auckland
Dr Nagham Al-
Mozany
Consultant Colorectal General SurgeonAuckland City Hospital Clinical Senior Lecturer University of Auckland
Bowel cancerMulti-discipline perspective
Dr Alasdair Patrick
Dr Nagham Al-Mozany
Dr Ben Lawrence
Overview
• Case history• Follow a patients battle with bowel cancer
– Risk factors for bowel cancer
– Options for screening• FOB, colonoscopy
• Bowel cancer screening program
– Symptoms & signs of bowel cancer
– Staging
– Treatment of bowel cancer depending on stage
Case History
• Mr FK
– 40 year old European man asks about screening for bowel cancer
– Fit and well
– No medications
– Smoker 10 per day for 10 years
– Family history
• Older sister had 3 polyps at colonoscopy aged 48
• Father died of bowel cancer aged 56
Presentation
Presentation
• Rectal bleeding + change in bowels in >55yo → more likely to be CR Ca
• Rectal bleeding + perianal Sx (itch / prolapse / pain) → more likely to be benign
New E-Referral PR Bleeding Pathway….
Coming to GP’s soon!
Developed by:• Dr. Nagham Al-Mozany, Colorectal and General Surgeon• Dr. Kathy McDonald, General Practioner & GP liaison Officer• Mr. Julian Hayes, Colorectal and General Surgeon
Auckland City Hospital
STAGING
• Staging is an estimate of the amount of penetration of a particular cancer
• It is performed for diagnostic and research purposes
STAGING
• Demonstrates metastatic disease
• Demonstrates local disease requiring pre-operative treatment– Rectal cancer
• Guides operative approach
• All cancer patients are discussed individually at a multidisciplinary team meeting
• Faster Cancer Track Pathway
STAGING
• Multiple systems for staging colorectal cancers depend on:
1. Extent of local invasion (T)
2. Degree of lymph node involvement (N)
3. Presence/Absence of distant metastasis (M)
• Definitive staging can only be done after surgery has been performed and pathology reports reviewed
Staging Adjuncts…Radiology
MRI Scan
CT scan(Chest, Abdomen, Pelvis)
STAGING SYSTEMSAJCC stage TNM stage
2002 6th edition TNM stage criteria for colorectal cancer (superseded by 2010 7th edition)[1][2]
Stage 0 Tis N0 M0Tis: Tumor confined to mucosa; cancer-in-situ
Stage I T1 N0 M0 T1: Tumor invades submucosa
Stage I T2 N0 M0T2: Tumor invades muscularispropria
Stage II-A T3 N0 M0T3: Tumor invades subserosa or beyond (without other organs involved)
Stage II-B T4 N0 M0T4: Tumor invades adjacent organs or perforates the visceral peritoneum
Stage III-A T1-2 N1 M0N1: Metastasis to 1 to 3 regional lymph nodes. T1 or T2.
Stage III-B T3-4 N1 M0N1: Metastasis to 1 to 3 regional lymph nodes. T3 or T4.
Stage III-C any T, N2 M0N2: Metastasis to 4 or more regional lymph nodes. Any T.
Stage IV any T, any N, M1M1: Distant metastases present. Any T, any N.
STAGING
• The broader stage of a cancer is usually quoted as a number I, II, III, IV derived from the TNM value grouped by prognosis; a higher number indicates a more advanced cancer and likely a worse outcome
Dr Alasdair PatrickGastroenterologist
Options for screening
• What is the aim?
– Cancer vs polyps
• Stool testing
– FOB
– iFOB
• Other technology
– CT colonography
• Colonoscopy
Cancer v polyps
• Bowel cancer: good candidate for screening as there is a treatable precursor lesion
There are different types of polyps
• Average risk asymptomatic adult
– 20-30% risk of polyps
• 1/3 of these have a polyp more than 10mm
• Two main types
– Serrated lesions
• New sub classification
– Adenomas
Serrated (saw tooth) lesions
• WHO classification (serrated lesions)
– Hyperplastic polyps
• 70-95%
– Sessile serrated polyps
– Traditional serrated adenoma
Hyperplastic polyps
• Identified 30 years ago
– Previously thought to have no malignant potential
• Now sub-classified
• Straight crypts
– Minimal distortion
– More serrated at top of crypt
– Common in left colon
Sessile serrated polyps
• Disorganised and distorted crypts
– Varying degrees of nuclear atypia
– Often find a mucus cap
– Mostly in right colon
• SSP/SSA are precursors of 1/3 CRC
– Autopsy studies find 25-50% prevalence
– More likely proximal and flat
– Account for disproportionate interval cancers
Adenomas
3 Histological types of adenoma
• A) Tubular adenoma
– Found in 30-50% of older adults
– Tumour cells form glands or gland like structures
• B) Tubulo-villous
– Mixture of villous and tubular morphology
– Increased malignant potential
Types of adenoma
• C) Villous adenoma
– Often larger
– Usually sessile
Risks of adenoma types
Cannot tell the type of adenoma on CTC-miss important prognostic information
Does size matter?
• Barium studies pre colonoscopy era
– Polyp > 1cm cancer risk
• 5 years 2.5%
• 10 years 8%
• 20 years 24%
– Flat or depressed lesions probably have higher risks (SSA)
What is the aim of screening?
• Detect only cancer
– FOB
– iFOB
• Detect cancer + polyps
– Colonoscopy
– Stool DNA
– CTC
– Colon capsule
• Detect and prevent cancer
– Colonoscopy
FOB testing
• The test card contains white paper impregnated with guaiac resin which turns blue in the presence of hemoglobin (after adding hydrogen peroxide, H2O2)
• The blue color results from oxidation of guaiac by H2O2 (the active ingredient in the developer fluid) in the presence of heme.
• The catalytic action of heme results from its peroxidase activity –animal heme in meat and plant peroxidases in certain foods also has peroxidase activity – which explains some of the false positive reactions that can occur.
• iFOB tests are more specific as they use antibodies to detect globin
Guaiac Resin
+Heme
+H2O2
Blue Color
Limitations of FOB
• A negative test result does not rule out intermittent bleeding or non-uniform distribution of blood in feces, and can result from high dose dietary or supplemental Vitamin C.
• A false positive result may be obtained on healthy persons due to dietary interferences (red meat), or medications (NSAIDs, corticosteroids, anticoagulants, cancer chemotherapeutics, and others).
• Does not detect polyps
11.6 x 31.5mm capsule with 172 degree image from each end
Adaptive frame rate 35/s-4/s
Clear liquid diet plus senna and 4L PEG plus boosts
Mixture of patients
88% egestion rate
Stool DNA
• Detect multiple individual DNA alterations
– APC
– KRAS
– P53
– BAT 26
• Still a work in progress
Role of CT colonography
• Positives for CTC– Is necessary in our endoscopist resource constrained environment
• Screening will add hugely to our waiting lists
– Great for incomplete colonoscopy• Technically challenging
• Obstructing lesions
– Great for the frail or co-morbid
– May increase participation in screening• Increased options for patient
My concerns regarding CTC
My concerns regarding CTC
• Small polyps can still be at increased risk of being advanced lesions
– In my experience CTC seems to underestimate polyp size
– We do not know about advanced pathology
– If we remove all polyps seen then costs and therefore benefits of CTC are greatly diminished as the initial test
• Incidental lesions
• Radiation risk
Do patients really prefer CTC?
– Bowel prep
– Rigid tube up the bum whilst awake!
Or do they prefer a pleasant, gentle and intimate
flexible camera insertion by a friendly Gastroenterologist?
Colonoscopy
• Remains the gold standard
• Finds cancer and polyps
• Removing polyps prevents future cancers
– Prevention is better than cure
National bowel cancer screening
Bowel cancer screening pilot
• Pilot using iFOB (OC-sensor, Eiken)
• Competitive RFP won by WDHB with support of ADHB and CMDHB
• WDHB residents
• 50 – 74 years of age
• Commenced October 17th 2011 until Dec 2015
• Two 2-year screening cycles
• Extended for another 2 years
Exclusion Criteria
• Colonoscopy in the last five years
• Previous colorectal cancer and/or in a
surveillance program
• Patients with UC or Crohn’s esp those
under surveillance
NZ bowel Screening Pilot
• Invite sent out on birthday
• Test kit –4 weeks later
• Results to GP/BSP (positive) – within 3 days
• Referrals for colonoscopy – within 10 days
• Colonoscopy – within 55 days
• Results (histology) to BSP within 10 days
• FSA if cancer within 10 days
• MDM within 20 days
Bowel Screening findings 2012-2015
•315 cancers in 303 patients•310 cancers/299 patients treated in public/private (8358 colos in 8187pts)
•43 cancers/39 patients treated in private
•171 males
•128 females
Bowel cancer screening
• Budget 2016
– $39.3 over 4 years for design, planning and set up
– Progressive roll out from mid 2017
• Narrowed criteria to 60-74 year olds
• 9 DHBs in 2018 and 8 in 2019
• There are significant resource issues– Each DHB could require 1 full time endoscopy theatre to meet demand
– 0.5 FTE surgeon also needed
Mr FK
• After a full discussion of his options
– Declined all screening
• 8 years later
– Develops PR bleeding
– Colonoscopy
• Find a large polyp
Stage 1 and 2: Gastroenterologist
• Three important considerations
– Ability to get a clear margin
– Lymphatic invasion
– Vascular invasion
• If any of these are compromised or the cancer is poorly differentiated then surgery is required
Ability to get a clear margin
• A pedunculated polyp containing a cancer can be snared off
• EMR
Ability to get a clear margin
• Endoscopic submucosal dissection (ESD)
Lymphatic and vascular invasion
• Lymphatic invasion– Looked for by pathologist
– Very few lymphatic's above the muscularis mucosa
• Vascular invasion– Looked for by pathologist
• Vascular markers may help – CD 31 and 34
Surgeon’s perspective
• All patients are discussed at MDT’s
Malignant Polyp or Early Ca
• Definition: Cancer invading into the submucosa
• Different classification systems:
1. Kikuchi (sessile polyps- sm1,2,3)
2. Haggitt (pedunculated polyps)
• Considered Early or T1
• Low risk- LN mets (<1%) EMR,TAMIS
• High risk-LN mets (>10%) needs surgery
Trans-anal minimally invasive surgery(TAMIS)- Novel techniques for early stage
cancers
Avoid Stomas?
Mr FK
• Missed repeat colonoscopy at 5 years
• Came back 9 years later
• Colonoscopy shows sigmoid tumour
– What next?
Surgical Options
Maximally invasive surgery Minimally invasive surgery
Complications
• Post-op mortality 2-5%
• Post-operative morbidity 30-40%– wound 10%
• wound dehiscence• wound infection• wound hematoma
– cardiorespiratory 10%– anastomotic dehiscence 5-15%– postoperative haemorrhage < 5%– stoma complications 10%– prolonged ileus 5%– urinary tract 10%– Sexual dysfunction varies 0-40 %
Mr FK
• Histology shows sigmoid adenocarcinoma
– T3 N1 M0
• Mismatch repair deficient
– B-Raf mutant
Stage 4 diffuse Stage 4 Oligo Stage 3
Oncology Perspective Stage 3 and 4
Adjuvant Chemotherapy
http://www.apple2.org.za/gswv/me/Boris/Genetech/Geneintro.html
Chemo destroys DNA so cancer cells can’t divide
Adjuvant Chemotherapy
ChemoP
ChemoL P
ChemoChemo L PL
ChemoChemo LP L
Mr FK
• 2 years later diffuse mets liver, lung, bone
ChemoP
Palliative therapy – not just chemo
Biomarkers determine choice
dMMRRas wtAny
Bevazicumab Cetuximab Pembrolizumab
Molecular therapies target growth pathways
Bevacizumab
Cetuximab
Checkpoint inhibitors show the cancer to the immune system
Pembrolizumab
Chemo 1 Chemo 2
Chemo 1 Chemo 2
Bevacizumab
Chemo 1 Chemo 2
Cetuximab Bevacizumab
Chemo 1 Chemo 2
Cetuximab Bevacizumab
Pembrolizumab
dMMRRas wt
Advances in median survival…
0 10 20 30 40 50 60
BSC
w CHEMO
w TARGET
w IMMUNE
Median Survival (months)
?
Mr FK
Chemo 1 Chemo 2
Cetuximab Bevacizumab
Pembrolizumab
Questions