Irritable bowel syndrome - interpreting a diagnosis
1. 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
3. 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
4. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Other symptoms
Gas and bloating
Visible abdomen swelling
Abdomen pain or discomfort
Heartburn
Back and muscle ache (fibromyalgia)
Irritable bowel syndrome
7. Is it irritable bowel syndrome ?
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
8. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Diagnostic approach to abdomen symptoms
Addressing patient’s concerns
History is very important
Examination:
BMI (weight, height)
Pale, jaundice
Mass in abdomen
Enlarged liver
Tenderness
Lumps (lymph nodes)
Rectum examination
9. Investigations - tools
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Addressing patient’s concerns
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
10. White blood cell
Red blood cell
Features of colon inflammation
Simple stool test
11. Warning signs: may not be IBS
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
12. Doctor’s role: a fine balance
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Not doing enough to
exclude
serious disease
Doing too many tests
Some may have risks
Cost
Balance patient’s concerns
with realities
13. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
I Functional
Motility disorder with visceral sensitivity
No structural abnormality
Irritable bowel syndrome
IBS- Constipation
IBS- Diarrhea
IBS- Constipation/Diarrhea
Some causes of abdomen pain
14. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
15. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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”
16. 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
17. Ito T, J Gastroenterol 2010
Symptoms in carcinoid patients
Diarrhea 4%
Constipation 10%
Abdomen pain 27%
Flushing 1%
18. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Long digestive tract
19. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
20. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Gastroscopy
21. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Colonoscopy
22. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Video capsule “endoscopy”
23. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Esophagus
Stomach
Duodenum
Small intestine
Large intestine
Gallbladder
Bile duct
Pancreas
Liver
Scans, endoscopic ultrasound
27. Challenges in IBS
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
28. 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%
31. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Non-functioning NET does not
produce hormone
Asymptomatic carcinoid
When NET grows bigger, can cause
pain, bleeding, obstruction
How does carcinoid(NET) cause diarrhea ?
32. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
How does carcinoid(NET) cause diarrhea ?
33. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
How does carcinoid(NET) cause diarrhea ?
34. USA
GI + pancreatic NET is 2.85 per 100,000
Total NET is 5 per 100,000
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Carcinoid
35. 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
36. Singapore Cancer Statistics 1993-2002
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
37. Singapore Cancer Statistics 1993-2002
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
300,000 cases IBS
(10% of 3 million)
38. 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
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
39. 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
Ito T, J Gastroenterol 2010
Incidence rates: West vs East
40. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
A test is available for NET:
Chromogranin A
41. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
The Perfect World - A Perfect Test
Sensitivity 100%
Specificity 100%
True Positive = disease present
True Negative = disease absent
42. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
The Real World
True Positive = disease present
True Negative = disease absent
False Positive = false alarm
False Negative = disease missed
43. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
The Real World
True Positive = disease present
True Negative = disease absent
False Positive = false alarm
False Negative = disease missed
44. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
45. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
46. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
47. 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
48. 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
49. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
50. Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
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
52. 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
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
53.
54. • 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 ?
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
55. Singapore Cancer Statistics 1993-2002
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Sitenumber cases Adeno-cancer NET-cancer
Rectum 3,893 115 (36%)
Lung 3,416 80
Colon 5,676 70 (22%)
Stomach 3,188 26 (7%)
Small intestine 95 24
Pancreas 510 8
Total cases 16,778 323
GI-NET cancer
Rectum + colon + stomach
account for 65% of all NET cancer
56. Singapore Cancer Statistics 1993-2002
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
Sitenumber cases Adeno-cancer NET-cancer
Rectum 3,893 115 (36%)
Lung 3,416 80
Colon 5,676 70 (22%)
Stomach 3,188 26 (7%)
Small intestine 95 24
Pancreas 510 8
Total cases 16,778 323
Arising from the large numbers of
gastroscopies and colonoscopies
performed daily, there is
opportunistic screening
60. 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
61. 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
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
62. 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
Yap Chin Kong Gastroenterology & Liver Clinic
For Digestive, Colorectal, Liver & Pancreatic Health
64. Arch Intern Med 2009;169(22):2078-2086
Radiation Dose Associated with
Common Computed Tomography
Examinations and the Associated
Lifetime Attributable Risk of
Cancer
65. 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
66. Doctors try our best
It’s not nice to be sick ....
But there are risks & benefits
In the diagnostic and
therapeutic journey
67. 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
68. Do I need a CgA test?
No!
High false positive results
I attended a talk on
carcinoid.
I am worried. I have no
symptoms
69. Do I need a CgA test?
No!
Unless symptoms are atypical
on periodic review
I have typical
IBS
symptoms
70. Do I need a CgA test?
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
71. Do I need a CgA test?
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 ?
72. Do I need a CgA test?
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 ?
73. 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
Relative risk is 5 fold higher than 30 years ago Absolute risk is rare 1:100,000 Analogy is if you have a 1 in million chance of winning the lottery, if you increase your chances 10 x, you still have an absolute risk of 10 in a million chance, which is still very small.