Irritable bowel syndrome - interpreting a diagnosis

Interpreting an Irritable
Bowel Syndrome Diagnosis
Yap Chin Kong Gastroenterology & LiverClinic
Dr Yap Chin Kong
Consultant Gastroenterologist
Hepatologist & Clinic Director
MBBS, MMed, MRCP, FRCP
@ Mount Elizabeth Medical Centre, Singapore

Irritable bowel syndrome
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Diagnostic criteria (Manning/Rome)
1 Abdomen pain relieved by defecation
2 Looser stools at onset of pain
3 Frequent stools at onset of pain
4 Abdomen distension
5 Passage of mucus in stools
6 Sensation of incomplete defecation

Other symptoms
Gas and bloating
Visible abdomen swelling
Abdomen pain or discomfort
Heartburn
Back and muscle ache (fibromyalgia)

Pain, diarrhea,
bloating etc
Hmmm...
IBS
Address patient’s symptoms

Address patient’s concerns
I’m concerned
of cancer -
my colleague
had it
A colonoscopy
will rule that out

Is it irritable bowel syndrome ?
Addressing patient’s concerns
1 Worried about serious disease
2 Wants to rule out colon cancer, inflammatory
bowel disease, celiac disease
3 Wants relief of symptoms: pain, diarrhea etc
4 Up to 10% of population have IBS

Diagnostic approach to abdomen symptoms
History is very important
Examination:
BMI (weight, height)
Pale, jaundice
Mass in abdomen
Enlarged liver
Tenderness
Lumps (lymph nodes)
Rectum examination

Investigations - tools
1 Blood, stool tests: anemia, inflammation,
celiac disease in Caucasian
2 Colonoscopy to exclude colon cancer,
inflammatory bowel disease, others
3 Ultrasound scan: liver, pancreas,
gallbladder, ovaries
4 Reserve list: Gastroscopy, video capsule,
CT scans

White blood cell
Red blood cell
Features of colon inflammation
Simple stool test

Warning signs: may not be IBS
1 Moderately severe pain alone
2 No relationship with bowel movement
3 Severe diarrhea or diarrhea alone
4 Passage of blood
5 Weight loss
6 Fever
7 Anemia

Doctor’s role: a fine balance
Not doing enough to
exclude
serious disease
Doing too many tests
Some may have risks
Cost
Balance patient’s concerns
with realities

I Functional
Motility disorder with visceral sensitivity
No structural abnormality
IBS- Constipation
IBS- Diarrhea
IBS- Constipation/Diarrhea
Some causes of abdomen pain

II Organic
Acid related: GERD, ulcer
Cancer ± diarrhea
Inflammatory bowel disease (Crohn’s, ulcerative colitis) ± diarrhea
Eosinophilic enteritis ± diarrhea
Ischemic colitis ± diarrhea
Diverticulitis ± diarrhea
Infections (ameba, tuberculosis) ± diarrhea
Celiac sprue ± diarrhea
Tropical sprue ± diarrhea
Stones in gallbladder or bile duct ± diarrhea
Carcinoid (neuroendocrine tumor) with liver metastases ± diarrhea
Carcinoid (neuroendocrine tumor) lung ± diarrhea (no pain)
Some causes of abdomen pain

IBS and NETs
 IBS does not transform or increase the risk of NET
 Patients with “IBS” and NET tumor may be due to
(i) wrong IBS diagnosis
(ii) correct IBS diagnosis + development of a new NET
sequentially
(iii) chance association simultaneously
“guilt by association” vs “cause and effect”

Features of carcinoid (NET)
Ito T, J Gastroenterol 2010
No symptoms 70%
Carcinoid syndrome 3%
Carcinoid syndrome
Flushing
Severe diarrhea
Crampy pain
Nausea, vomiting
Wheezing

Symptoms in carcinoid patients
Diarrhea 4%
Constipation 10%
Abdomen pain 27%
Flushing 1%

Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Long digestive tract

Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Long digestive tract
We have the technology to
examine the entire digestive system
from mouth to anus

Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Gastroscopy

Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Colonoscopy

Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Video capsule “endoscopy”

Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Scans, endoscopic ultrasound

Endoscopic ultrasound scan revealed two
1 cm size tumors ? NET

Challenges in IBS
1 Common condition 10% population affected
2 Not always an easy diagnosis to make with complete confidence
3 Because IBS is common, we get it right most of the time
4 Challenge is to identify the “IBS-like” case that is not really IBS
5 One consultation is not enough
6 Follow up is important to look for evolution and re-evaluate
7 “Difficult IBS” gets investigated the most
8 Correctly diagnosed “IBS” does not prevent the occurrence of
another disease later on

Given a case study, willingness to diagnose
IBS on history & physical examination alone
Am J Gastroenterol 2010;105:848-
Yes No Unsure
IBS experts 70% 7% 23%
Community
gastroenterologists
52% 3% 45%
General internal
medicine physicians
34% 7% 59%
Nurse practitioners 41% 9% 50%

Colon cancer (Singapore)
1:20 life time risk

Non-functioning NET does not
produce hormone
Asymptomatic carcinoid
When NET grows bigger, can cause
pain, bleeding, obstruction
How does carcinoid(NET) cause diarrhea ?

Functioning NET produces hormone
(serotonin)
Hormone in intestine goes to liver
Hormone is destroyed by liver
No hormone in blood, therefore no
diarrhea
Asymptomatic carcinoid

Production of hormone by tumor
metastases in the liver
Hormone from the liver is released
into the blood
Hormone in blood causes diarrhea
Gastrointestinal carcinoids (NETs)
present late by the time diarrhea
occurs
OR
NET in lung produces hormone that is
released in the blood therefore causes
diarrhea

USA
GI + pancreatic NET is 2.85 per 100,000
Total NET is 5 per 100,000
Carcinoid

Colon cancer (Singapore)
Carcinoid, NET (USA)
5 per 100,000
(male+female)
38 per
100,000
(male+female)
Carcinoid, NET (Singapore)???
Incidence Statistics 1993-2002

Singapore Cancer Statistics 1993-2002
Sitenumber cases Adeno-cancer NET-cancer
Rectum 3,893 115
Lung 3,416 80
Colon 5,676 70
Stomach 3,188 26
Small intestine 95 24
Pancreas 510 8
Total cases 16,778 323

Rectum 3,893 115
Lung 3,416 80
Colon 5,676 70
Stomach 3,188 26
Pancreas 510 8
300,000 cases IBS
(10% of 3 million)

Why is there a difference ?
• Singapore 300-400 cases NET-cancer over 10
years.
• If we applied USA figures, we expect about 2,000
cases NETs over 10 years
• Possible reasons
(i) Real differences between East and West
(ii) Under diagnosed
(iii) Under reported: NET-cancer is notifiable, but
NET is not. More study needed

P-NET 0.32/100,000 1.01/100,000
GI-NET 2.53/100,000 2.10/100,000
Total 2.85/100,000 3.11/100,000
Yao JC, J Clin Onco 2008
Incidence rates: West vs East

A test is available for NET:
Chromogranin A

The Perfect World - A Perfect Test
Sensitivity 100%
Specificity 100%
True Positive = disease present
True Negative = disease absent

The Real World
True Positive = disease present
True Negative = disease absent
False Positive = false alarm
False Negative = disease missed

Test A for disease X
Test 1,000 people. Assume disease X is present in
1% = 10 people
Sensitivity = 85%
Specificity = 85%, false positive = 15%
85/100 x 10 = 8.5 have disease X (true positive)
Number of false positive tests is
15/100 x 1,000 = 150 persons
Total = 159 positive tests

Test B for disease X
Test 1,000 people. Assume disease X is present in
1% = 10 people
Sensitivity =98%
Specificity = 98%, false positive = 2%
98/100 x 10 = 9.8 have disease X (true positive)
Number of false positive tests is
2/100 x 1,000 = 20 persons
Total = 30 positive tests

What to do with a positive test?
Further tests
Scans, Bronchoscopy, Gastroscopy, Colonoscopy, Biopsy
True Positive test
Disease X
False Positive test
Normal people
Test A = positive tests
1,000
tested
Disease X = 10
Normal = 990

Sensitivity 85% Specificity 85%
1,000 persons True + (85%) False + (15%)
0 disease 0 150
10 disease (1%) 8.5 150
100 disease
(10%)
85 150
500 disease
(50%)
425 150
Test A for disease X

Sensitivity 98% Specificity 98%
1,000 persons True + (98%) False (2%)
0 disease 0 20
10 disease (1%) 9.8 20
100 disease
(10%)
98 20
500 disease
(50%)
490 20
Test B for disease X

Principles of testing
1 High occurrence of disease - high pick up rate
2 Low occurrence of disease - low pick up rate
3 Low occurrence disease, most positive tests are false
positive
4 High occurrence disease, most positive tests are true
positive
4 More people tested - more disease found
5 More people tested - more false positive tests found
6 Positive test needs further tests to differentiate true disease
from a false alarm

Principles of testing
1 Choosing a high risk group (with high occurrence of
disease) will increase the yield and reduce false positive
2 High risk group for NET tumor is a family history of NET
tumor
3 “IBS” is not recognized as a high risk group for
screening

Rectum carcinoid confirmed
CgA normal (false negative test)

Carcinoid (neuroendocrine) tumor
• NET is out there
• Not every type of pre-cancer or cancer can be detected
early with screening
• There are benefits and harm from screening
a balance has to be achieved
• Testing in patient with symptoms = diagnostic testing
• Testing in healthy person with no symptoms = screening

• Promote and ride on colon cancer screening which is on-
going. Opportunistic screening for gastric, rectum and
ileum NETs during gastroscopy and colonoscopy for other
reasons
• Small intestine NETs are nearly impossible to diagnose
early
• Consider the possibility of the condition in those with
• prominent diarrhea (mimic IBS)
• facial flush
• wheezing (mimic asthma)
• Unfortunately these symptoms indicate late metastatic
disease for NET in the gut and are rare
• May be early disease for NET in the lung
What can we do now ?

Rectum 3,893 115 (36%)
Lung 3,416 80
Colon 5,676 70 (22%)
Stomach 3,188 26 (7%)
Pancreas 510 8
GI-NET cancer
Rectum + colon + stomach
account for 65% of all NET cancer

Rectum 3,893 115 (36%)
Lung 3,416 80
Colon 5,676 70 (22%)
Stomach 3,188 26 (7%)
Pancreas 510 8
Arising from the large numbers of
gastroscopies and colonoscopies
performed daily, there is
opportunistic screening

Managing your risks
We see examples of risk every day

Managing your risks
• Risk is part of medical tests and treatment
• Weigh “risks” vs “benefits”: test vs non-test
• Weigh “risks” vs “benefits”: treatment vs non-
treatment
Choose your doctor
Experience with carcinoid
Don’t hurry colonoscopy:
tumors are small
Track record

Risk of colonoscopy
Sedation risk
•For maximum safety, comfort, perform in a center
with monitoring facilities
•Get a doctor who is experienced, good track
record: personal no sedation mishaps in 20 years,
>10,000 procedures
•Colonoscopy is possible without sedation
•Awake colonoscopy - mild discomfort - case by
case basis

Risk of colonoscopy
Procedure risk:
•Perforation, bleeding. Get a doctor with
experience, good track record: personal zero
perforation rate in 20 years
•Good colonoscopy technique

Arch Intern Med 2009;169(22):2078-2086
Radiation Dose Associated with
Common Computed Tomography
Examinations and the Associated
Lifetime Attributable Risk of
Cancer

Age 20 yr Age 40 yr Age 60 yr
F M F M F M
CT abdomen 250 330 460 498 700 660
CT coronary 150 390 270 595 420 790
CT brain 4,630 7,350 8,100 11,080 12,250
14,680
CT colon Not analysed
Number of CT scans to give rise to 1 cancer
Arch Intern Med 2009;169(22):2078-2086

Doctors try our best
It’s not nice to be sick ....
But there are risks & benefits
In the diagnostic and
therapeutic journey

First do no harm
Given an existing problem, it may be
better not to do something, or even do
nothing, than to risk doing more harm
than good
Human acts with good intentions may
have unwarranted consequences

Do I need a CgA test?
No!
High false positive results
I attended a talk on
carcinoid.
I am worried. I have no
symptoms

No!
Unless symptoms are atypical
on periodic review
I have typical
IBS
symptoms

Maybe!
Diagnose the cause of
diarrhea: blood, stool tests,
colonoscopy, biopsies,
± CT scan
If suspect NET do CgA test
I have persistent
diarrhea for one
month and lost
weight

I have a family
member with
carcinoid
Yes!
Gastroscopy, colonoscopy
Gallium PET scan baseline?
How frequent? Annually?
Q: CgA is negative, does it
mean I am safe ?

Dr Yap performed a
colonoscopy. He found and
removed an incidental
rectum carcinoid
Yes!
Up to 25% have another tumor
Gastroscopy, colonoscopy
Gallium PET scan baseline?
How frequent? Annually?
Q: CgA is negative, does it mean
I am cured ?

Diarrhea & pain can be a challenging
diagnosis
NETs in Singapore:
Unanswered questions
More research and statistics needed
Be mindful of the possibility but not over-react
Maintain a balanced approach and perspective
Maintain patient-centric focus

IBS NETColon cancer
Other causes
IBS symptoms

He who has health has
hope,
He who has hope has
everything

Wishing everyone good
health
Thank you!
www.gastroliver.com.sg

Irritable bowel syndrome - interpreting a diagnosis

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