Statistical modeling in pharmaceutical research and development.
Am 11.20 oxentenko
1. GI Disorders in Women:
Clinical Pearls
Amy S. Oxentenko, MD, FACP, FACG
Division of Gastroenterology and Hepatology
Mayo Clinic, Rochester, MN
March, 2012
2. Disclosure of Financial Relationships
Amy S. Oxentenko, MD, FACP, FACG
Has no relationships with any entity
producing, marketing, re-selling, or
distributing health care goods or services
consumed by, or used on, patients.
4. A 32 y/o female presents for evaluation of “diarrhea” and
abdominal pain that she has had for 5 years. She gets lower
abdominal pain and bloating 1-2 times per week. On those
days, she reports 3-5 loose stools, predominantly in the
morning or after meals. Stools are non-bloody, non-greasy
and never nocturnal. Stooling brings relief of her pain. She
denies weight loss. PMH is unremarkable. She takes no
meds. She has no family hx of GI problems. Exam is normal.
Which of the following is the next best step?
A. No further tests; reassurance
B. CBC & IgA tissue transglutaminase
C. Stool cultures
D. EGD w/ small bowel biopsies
E. Colonoscopy w/ random biopsies
5. A 32 y/o female presents for evaluation of “diarrhea” and
abdominal pain that she has had for 5 years. She gets lower
abdominal pain and bloating 1-2 times per week. On those
days, she reports 3-5 loose stools, predominantly in the
morning or after meals. Stools are non-bloody, non-greasy
and never nocturnal. Stooling brings relief of her pain. She
denies weight loss. PMH is unremarkable. She takes no
meds. She has no family hx of GI problems. Exam is normal.
Which of the following is the next best step?
A. No further tests; reassurance
B. CBC & IgA tissue transglutaminase
C. Stool cultures
D. EGD w/ small bowel biopsies
E. Colonoscopy w/ random biopsies
6. Be Comfortable Diagnosing IBS
Spiller RC, et al. Am J Gastroenterol 2010:105;775-75.
Brandt LJ, et al. Am J Gastroenterol 2009;104:S1-35.
8. Clinical Pearl
Diarrhea-predominant irritable bowel
syndrome is a diagnosis that can be
made with little exclusionary testing
required, other than a CBC and IgA tTG,
in the absence of alarm symptoms.
10. A 38 y/o female presents to the ER with recurrent abdominal pain,
nausea and bilious vomiting. Six months ago, she had a Roux-en-Y
gastric bypass for obesity. She has had 3 episodes in 1 month.
Pain is crampy, periumbilical, and crescendos over 1-2 hours and
is relieved after vomiting undigested food and bilious fluid. During
the last 2 episodes, ER eval with labs (CBC, liver biochemistries),
abdominal radiographs and RUQ ultrasounds were normal. She
takes a MVI w/ iron, thiamine, calcium, vitamin D and B12, but no
other meds. No other PMH. Her gallbladder was not removed w/
the laparoscopic bypass.
Which of the following is the most likely cause of symptoms?
A. Overeating
B. Biliary colic
C. Internal hernia
D. Stenosis of the gastric pouch
E. Medication side effect
11. A 38 y/o female presents to the ER with recurrent abdominal pain,
nausea and bilious vomiting. Six months ago, she had a Roux-en-Y
gastric bypass for obesity. She has had 3 episodes in 1 month.
Pain is crampy, periumbilical, and crescendos over 1-2 hours and
is relieved after vomiting undigested food and bilious fluid. During
the last 2 episodes, ER eval with labs (CBC, liver biochemistries),
abdominal radiographs and RUQ ultrasounds were normal. She
takes a MVI w/ iron, thiamine, calcium, vitamin D and B12, but no
other meds. No other PMH. Her gallbladder was not removed w/
the laparoscopic bypass.
Which of the following is the most likely cause of symptoms?
A. Overeating
B. Biliary colic
C. Internal hernia
D. Stenosis of the gastric pouch
E. Medication side effect
15. Early Emergent Complications
• Anastomotic leaks
– Early complication
– Only feature may be
unexplained tachycardia
• Internal hernias
– Occurs early or late
– Nausea, vomiting (? bilious)
– Increased w/ laparoscopy;
only occurs with bypass
• Both need surgery!!!
Klein S, et al. Gastroenterology 2002;123:882-932.
16. Other Common Complications
• Marginal ulceration
– May cause bleeding or
stricture at G-J site
– May create stomal stenosis
– ? NSAIDs, ? smoking
• Bleeding
– Can occur at any
anastomotic site
– Think of remnant stomach
and duodenum
– After routine EGD, may need
GI expertise to evaluate
17. Other Common Complications
• Biliary stone disease
– ERCP scope 124 cm; cannot
reach papilla in RYGB pts
• Typical Roux limb 100-150 cm
– Approach dependent on clinical
acuity and local expertise
papilla
• Nutritional deficiencies
– Iron, B12, Ca++, vitamin D
– Folate (give if childbearing)
– Thiamine (esp 1st 6 months)
18. Clinical Pearl
There are many potential structural,
absorptive and nutritional
complications of bariatric surgery;
knowledge of the post-bariatric
anatomy is essential in being able
to effectively manage these
patients.
20. 34 y/o female referred for “IBS” who is 16 weeks
pregnant. She had diarrhea in teens which resolved in
her 20’s and recurred early in pregnancy. Has 4-6 BM
daily with nocturnal stools. No abdominal pain. Takes
a prenatal MVI, iron and levo-thyroxine. Her pre-
pregnancy BMI = 17, with 5 lb weight gain thus far.
Conceived her baby with IVF. Her TSH is normal.
Which of the following is the next best step?
A. Tissue transglutaminase IgA
B. Colonoscopy
C. Begin scheduled loperamide
D. Stool bacterial cultures
E. Begin nortriptyline
21. 34 y/o female referred for “IBS” who is 16 weeks
pregnant. She had diarrhea in teens which resolved in
her 20’s and recurred early in pregnancy. Has 4-6 BM
daily with nocturnal stools. No abdominal pain. Takes
a prenatal MVI, iron and levo-thyroxine. Her pre-
pregnancy BMI = 17, with 5 lb weight gain thus far.
Conceived her baby with IVF. Her TSH is normal.
Which of the following is the next best step?
A. Tissue transglutaminase IgA
B. Colonoscopy
C. Begin scheduled loperamide
D. Stool bacterial cultures
E. Begin nortriptyline
22. General and GI Manifestations
of Celiac Disease
General Gastrointestinal
Short stature Diarrhea, steatorrhea
Weight loss* Flatulence, distension
Failure to thrive Abdominal discomfort
Lethargy Anorexia, nausea, vomiting
Delayed puberty Constipation**
Edema Angular cheilosis, glossitis
Rubio-Tapia A, Murray JA. * 10%+ obese
Curr Opin Gastroenterol 2010; 26:116-22. ** 20% constipated
23. Extraintestinal Manifestations:
Celiac Disease
Category Examples
Hematologic Anemia (iron*, B12, folate); functional asplenia (HJ-bodies)
Musculoskeletal Osteopenia/osteoporosis; osteomalacia; arthropathy
Neurologic Seizures; peripheral neuropathy; ataxia
Reproductive Infertility; recurrent miscarriages
Skin Dermatitis herpetiformis
Other Enamel defects; abnormal liver biochemistries; vitamin-
deficient states, cardiomyopathy, depression/mood
•*Prevalence of CD in pts with IDA:
•3-9% (no GI sxs)
•10-15% (GI sxs)
Rubio-Tapia A, Murray JA. Curr Opin Gastroenterol 2010; 26:116-22.
24. How to Diagnose Celiac Disease
• TTG IgA single best screening test
– IgA levels not warranted for all
• Small bowel biopsies in:
– All with positive serologies
– Negative serology but clinical suspicion
– Iron deficiency anemia
– Other unexplained extraintestinal features
• Treatment: Lifelong, strict gluten-free diet
– Wheat, barley, rye (oats for 1st year)
25. Celiac Follow-Up
• Baseline:
– Dietician, DEXA (latter for adults only)
– CBC, folate, ferritin, B12, Ca++, zinc, copper, vit
D, INR, retinol, albumin, ALT, alk phos
• Follow-up visit 3-6 months:
– Assess clinical sxs, serologies
• Annual visits thereafter:
– Assess clinical sxs, serologies, dietician
– Follow-up abnormal labs; DEXA if first abnormal
• Repeat biopsies ONLY for those:
– Asymptomatic presentations
– Persistent or recurrent sxs
Leffler D. JAMA
26. Clinical Pearl
Celiac disease now commonly
presents with “atypical” or
extraintestinal features; heightened
awareness of these features is key to
thinking of the diagnosis.
28. 28 y/o female presents with constipation for 5 years.
Reports one BM every 5-7 days. She has to strain and
has a sense of incomplete evacuation. She has had to
digitalize on occasion to evacuate a stool. No blood.
Had a significant tear with her vaginal delivery 6 years
ago, requiring forceps delivery. No FHx colon cancer.
Weight stable. Exam normal with the exception of
paradoxical contraction of the external anal sphincter.
What is the most likely diagnosis?
A. Irritable bowel syndrome
B. Slow-transit constipation
C. Rectal prolapse
D. Hirschsprung’s
E. Pelvic floor dysfunction
29. 28 y/o female presents with constipation for 5 years.
Reports one BM every 5-7 days. She has to strain and
has a sense of incomplete evacuation. She has had to
digitalize on occasion to evacuate a stool. No blood.
Had a significant tear with her vaginal delivery 6 years
ago, requiring forceps delivery. No FHx colon cancer.
Weight stable. Exam normal with the exception of
paradoxical contraction of the external anal sphincter.
What is the most likely diagnosis?
A. Irritable bowel syndrome
B. Slow-transit constipation
C. Rectal prolapse
D. Hirschsprung’s
E. Pelvic floor dysfunction
30. How to Define Constipation?
• In the past:
– < 3 stools per week
• More recent:
– Effort to defecate
– Consistency and form
• Bristol stool form scale
• Correlates w/ transit
times
Brandt LJ, et al. Am J Gastroenterol 2005;100:S5-21.
31. 3 Subtypes of Primary
Constipation
• Slow-transit constipation
– Prolonged transit due to myopathy or
neuropathy
• Pelvic floor dysfunction
– Also referred to as dyssynergic defecation
– Impaired abdominal, rectoanal and pelvic floor
muscle coordination
• Constipation-predominant IBS
– Pain or discomfort a predominant symptom;
transit and pelvic function normal
Bharucha AE, Wald AM. Am J Gastroenterol 2010;105;786-94.
32. Alarm Features for
Constipation?
• Age > 50 years
• Short duration symptoms (< 6 months)
• Family hx colorectal cancer
• Blood in stools
• Weight loss
*** These patients need an evaluation
which includes colonoscopy ***
33. Work-Up for Constipation
• CBC, calcium, TSH, fasting glucose
• If ≥ 50 or alarm features colonoscopy
• If features of pelvic floor dysfunction
a) Anorectal manometry/balloon expulsion
b) Colonic transit study
• 1) radio-opaque markers, or
• 2) scintigraphy, or
• 3) pH capsule
34. Clinical Features of
Pelvic Floor Dysfunction
• Risk factors: childbirth, abuse, chronic
constipation, other pelvic trauma
• Excessive straining, toilet rocking or
repositioning
• Sense of incomplete evacuation
• Sense of anorectal blockage*
• Digitation for stool evacuation*
Bharucha AE, Wald AM. Am J Gastroenterol 2010;105;786-94.
35. Examination Features of
Pelvic Floor Dysfunction
• Abnormal perineal descent
• Abnormal resting and squeeze tone
• Paradoxical contraction of
puborectalis or external anal
sphincter
Bharucha AE, Wald AM. Am J Gastroenterol 2010;105;786-94.
36. Pelvic Floor Dysfunction
Normal Rest Normal defecation
Those with pelvic floor dysfunction have paradoxical
contraction of puborectalis and external sphincter
37. Management of Pelvic Floor
Dysfunction
• Refer for biofeedback program
• Significantly improves (for at least 1 year):
• Spontaneous BMs
• Dyssynergia
• Balloon expulsion time
• Colonic transit time
• If there is concomitant prolapse, fix pelvic
floor dysfunction first
Bharucha AE, Wald AM. Am J Gastroenterol 2010;105;786-94.
Rao SSC, et al. Am J Gastroenterol 2010;105:890-6.
38. Clinical Pearl
Constipation associated with a sense of
anorectal blockage, the need for digitation
to evacuate stool, and paradoxical
contraction of the puborectalis is
suggestive of pelvic floor dysfunction;
anorectal manometry is indicated.
40. A 58 year old female presents for an evaluation of diarrhea that
has been present for 4 months. She has crampy pain, bloating
and weight loss of 10 pounds. She denies any blood in her
stool, but notes it to be foul smelling and greasy appearing. No
recent medication changes. No travel. She does have a history
of prior cervical cancer 4 years ago, s/p resection,
chemotherapy and radiation. Labs reveal a hemoglobin of 10.4
g/dL, MCV of 102 fL and albumin of 3.1 g/dL. She states that
dairy avoidance has somewhat, but not fully, helped. TTG IgA is
normal. Colonoscopy with ileal inspection is normal.
Which of the following is the next best step?
A. CT of the pancreas
B. Lactose breath test
C. PET scan
D. Lactulose breath test
E. Flex sig w/ biopsies
41. A 58 year old female presents for an evaluation of diarrhea that
has been present for 4 months. She has crampy pain, bloating
and weight loss of 10 pounds. She denies any blood in her
stool, but notes it to be foul smelling and greasy appearing. No
recent medication changes. No travel. She does have a history
of prior cervical cancer 4 years ago, s/p resection,
chemotherapy and radiation. Labs reveal a hemoglobin of 10.4
g/dL, MCV of 102 fL and albumin of 3.1 g/dL. She states that
dairy avoidance has somewhat, but not fully, helped. TTG IgA is
normal. Colonoscopy with ileal inspection is normal.
Which of the following is the next best step?
A. CT of the pancreas
B. Lactose breath test
C. PET scan
D. Lactulose breath test
E. Flex sig w/ biopsies
46. Treatment of SIBO
• Modify underlying risk factor (minority)
– Diabetes, surgery, etc.
• Nutritional support
– Correct deficiencies (vit B12, vit D, Ca++)
– Lactose malabsorption (secondary)
• Antibiotic therapy
– Single 7-10 days (46-90% improve for months)
– Recurrence 44% at 9 months
– Some may need repeat courses (1 week/month)
47. Treatment for Bacterial Overgrowth
Ciprofloxacin 250 mg BID
Norfloxacin 800 mg QD
Metronidazole 250 mg TID
Trimethoprim-SMX 1 DS BID
Doxycycline 100 mg BID
Tetracycline 250 mg QID
Amoxicillin-clavulanate 500 mg TID
Rifaximin 800-1200 mg QD
Quigley EMM, et al. Infect Dis Clin N Am 2010; 24: 943-59.
