GI GRAB BAG
| PROBIOTICS IN CLINICAL PRACTICE: FACT OR FANTASY? —Robert G. Martindale, MD, PhD, Professor of Surgery,
Oregon Health and Science University, Portland, OR
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| Probiotics now science: for 20 yr, covered in lay press and seen as homegrown wisdom (eg, eat yogurt when taking antibiotics);
1908 Nobel prize won by authors of study showing populations that routinely ate fermented food products (eg,
yogurt, sauerkraut) lived longer (studied populations that lived ≥100 yr)
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| Veterinary use of probiotics: European Union (EU) banned use of antibiotics in animals; use of probiotics increasing
in Europe; achieve same weight gains (≈10%) with probiotics as with antibiotics
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| Beneficial bacteria: ≈600 species of primarily anaerobic bacteria in human gastrointestinal (GI) tract; definition of
probiotics—live microorganisms of human origin, viable, hardy, acid-stable, and biostable that adhere to mucosa and provide
some benefit to host; origin—infant inoculated as it passes through birth canal; by ≈1 yr of age, humans have developed
flora that stay with them for life; twins separated at birth have similar flora; obligate anaerobes mostly emerge after
weaning; germ-free animals—colons ≈4 times bigger; mucosal development marginal; risk for cancers much higher
(thought mainly due to blood supply); caloric intake ≈20% higher to maintain same weight; so clearly, bacteria in human
colon beneficial
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| Bacteria in stomach: unless patient taking proton pump inhibitors (PPIs), low bacterial concentration in stomach (102 ;
100 to 1000/mL); in colon, 1013 /mL; can be good bacteria (eg, Lactobacillus, Bifidobacteria); Pseudomonas and more
aggressive gram-negative bacteria present but kept in check by other bacteria via competitive inhibition
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| Bacteria in colon: surface area 400 m2 ; ≈100 trillion bacteria; 2 million genes in bacterial genome living inside GI tract,
and ≈35,000 genes in human genome; significant cross-talk between them; known that in germ-free animals, reinstilling
single bacterium into GI tract turns on ≈100 genes within ≈3 hr; recent research shows bacteria and human host have relationships
not known until last few years; when large animal (70-kg pig) injected with epinephrine, norepinephrine, or
cortisol, within 30 min, bacteria living in colon express adhesive molecules that allow bacteria to become aggressive and
adhere to mucosa; only after host becomes compromised do bacteria sense change in pH, temperature, and redox potential
and become aggressive
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| Inflammatory bowel disease (IBD): global perspective shows areas with higher bacterial content in diet have very
low prevalence of IBD; animal models for IBD show if no bacteria present, no colitis; these models develop colitis similar
to that seen in humans; if normal resident bacteria restored, they all get colitis, showing clear but unknown association
between bacteria and ulcerative colitis (UC); known that if normal cecal bacteria instilled into HLA-B27 transgenic
mouse, aggressive colitis results; giving cecal bacteria plus Lactobacillus GG (LGG; Culturelle; Centers for Disease
Control and Prevention [CDC] recommends for traveler’s diarrhea), protection results; now probiotics and prebiotics
added to list of agents used to treat IBD; protective bacteria significantly decreased in Crohn’s and UC patients
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| Pouchitis: paper published in Gasteroenterology in 2000 looked at use of probiotics to prevent pouchitis; used high-potency
probiotic (450 billion live bacteria per packet) that contained Bifidobacterium and several strains of Lactobacillus,
among others; consensus that in severe refractory pouchitis, probiotic drug of choice; probiotic therapy recommended by
Crohn’s and Colitis Foundation of America (CCFA)
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| Crohn’s disease: world literature shows some support, some negative, and some neutral; differences due to lack of standardization
of type of bacteria used; multistrain products now recommended; UC—good data starting in 1997
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| Prebiotics: substrate for probiotics; 2 studies show increased intake of soluble fiber supplement (eg, Benefiber) before
travel decreases incidence of traveler’s diarrhea; as Lactobacillus and other bacteria metabolize partially soluble fibers,
they produce more acid and lower pH in right colon at mucosal interface (normally 7.23 to 7.27); single broad-spectrum
antibiotic increases pH to ≈7.35 in right colon and pathogens flourish; idea that probiotic maintains low pH at which toxicogenic
Escherichia coli cannot survive
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| Scientific mechanisms: for pathogenic enteric bacteria, probiotics probably work mainly by inhibiting growth; they occupy
ecologic niche, preventing bacteria from growing, but they also secrete antibacterial proteins; for IBD, probiotics
induce interleukin (IL)-10 and transforming growth factor (TGF)- β and decrease expression of NF-kappa B; good scientific
data now support emerging clinical outcomes
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| Irritable bowel syndrome (IBS): nothing new; decreased bloating and inflammation; no hard data, although many
report probiotics make big difference
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| Clostridium difficile: best data yet for refractory C difficile; incidence increasing; risk factors include GI procedures, antibiotics,
hospital stay, ie, any disruption of colonic microflora; studies using several probiotics for C difficile show variety
of outcomes; Cochrane analysis—23 studies (2000 adult and pediatric patients); found probiotics lower risk for C
difficile diarrhea and decrease mean duration of diarrhea; specificity—several species (Lactobacillus plantarum, Lactobacillus
rudiae, and Lactobacillus casei) make 54 kD protein that destroys C difficle toxins A and B; supports argument
that strains of bacteria in probiotic need to be taken into account; some yogurts (eg, Yoplait) contain bacteria for
production and flavor, not for function; Lactobacillus acidophilus in yogurt stays alive 7 to 14 hr; L plantarum, L casei,
and L rudiae more for function and stay alive much longer; adherence to mucosa seems key
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 | Refractory C difficile infections: most patients respond to metronidazole (Flagyl) as first choice or po vancomycin; if patient
npo—motility in question; known that intravenous (IV) Flagyl effective in colon because of enterohepatic circulation;
tube delivery systems now enable clinician to deliver probiotics through rectal tube
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| Surgical setting: recent prospective blinded trial in Transplantation showed decrease in infections after hepatic transplantation
from 48% to 3%; in abdominal surgery, infections reduced (10% vs 30%); prospective randomized trial in pancreatic
necrosis (if infected, mortality increases from 6% to 50%) found that giving probiotics decreases infections from 30% to
4.5%; results repeated by another group using L plantarum
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| Technical advances: at 2 centers, gene for IL-10 production spliced into lactobacilli grown in large cultures; patients
with UC given solution of bacteria or yogurt drink containing bacteria, thus enabling production of IL-10 (anti-inflammatory
cytokine) at site of inflammation, ie, at mucosa; future uses of probiotics—Lactobacillus jensenii secretes CD4 protein
that inhibits HIV entry into target cells; fermented milk products containing this organism may help decrease spread
of HIV
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| TRANSGASTRIC AND TRANSCOLONIC THERAPY FOR INTRAPERITONEAL DISEASE —Bruce V. MacFayden,
MD, Professor of Surgery, and Chairman, Department of Surgery, Medical College of Georgia, Augusta
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| Historical perspective: laparoscopy started ≈1901 (animals); then trocars developed for introduction of instruments
into abdominal cavity; Veress needle allowed insufflation of abdomen; development of insufflator allowed visualization
of abdomen and ability to maneuver in cavity; 1966 development of Hopkins rod-lens system improved visualization;
1986 development of computer chip television camera for attachment to laparoscope; 1986 development of flexible endoscopic
sewing machine; in 1987, laparoscopic cholecystectomy developed; endosocpic endoluminal therapy appeared
in 2000
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| Transluminal surgery: concept dates to 2003; per oral or per rectum flexible endoscopic transgastric, transcolonic entry
into peritoneal cavity for diagnosis and therapy; purpose to avoid skin incisions, reduce infection, shorten hospitalization
(outpatient preferred), reduce cost, and lower morbidity and mortality
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| Transgastric procedures: liver biopsy; cholecystectomy; splenectomy in animals (pigs) in which spleen brought out
through stomach; ligation of fallopian tubes; gastrojejeunostomies; full-thickness removal of colonic tissue; appendectomy;
vertical banded gastroplasty recently presented during Digestive Disease Week 2006; full excision of stomach and
colonic wall; technical challenge how to close
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| Surgical equipment: generally use forward viewing double-channel endoscope, cutting wire, sphincterotome, balloon
dilator (make small hole in stomach, then dilate), endoscopic grasping forceps, polypectomy snares, endoloops, endoclips,
and sterile overtube; equipment not very strong; further development of equipment needed
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| Preparation: animals put on enteral liquid diet; usually fast for 12 hr; general endotracheal anesthesia; disinfection important;
use sterile overtubes, and sterile flexible endoscope preferred; topical and parenteral antibiotics
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| Equipment available now: endoscopic sewing machine; pledgets; pin and cylinder locking device; linear and circular
staplers now developed for endoscopic use; T-bar fasteners sometimes used for peg placement; buttons and plates; magnets,
particularly in gastrojejeunostomy; biofragmentable compression devices (Murphy button); suturing approximation devices
using endoscopic ultrasonography; full-thickness resection devices
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| Current issues: sterility; visualization; spatial orientation; 30º endoscope; brain adapts to 3-dimensional orientation; access
and closure; need retracting equipment to expose area and to see more clearly (eg, colon against gallbladder carries higher risk
for perforation); expect radical redesign of endoscope in next 5 yr
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| Suturing and knot tying: always thought essential for laparoscopy; now mechanical devices proving effective; combinations
of transabdominal, transluminal instrumentation placement; must know suturing and knot tying and ways to get
access, retraction, and exposure
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| USGI ShapeLock endoluminal therapy: “glorified overtube”; retains shape; can put into many shapes; can contain
modified flexible endoscope; different grasping devices; instrument can move around and visualize different organs, eg, gallbladder
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| Transanal endoscopic microsurgery (TEM): can completely excise large tumors in rectum up to 15 to 20 cm
from anal verge; potentially very complicated; having renaissance among some colorectal surgeons; much instrumentation;
can do full-thickness excisions; if extended, could achieve transcolonic access; experimental appendectomy via
TEM already carried out in animals
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| Conclusions: more questions than answers; safety of procedures needs assessment; improved operative time likely as
procedures improve; outpatient procedures should be goal; proceed cautiously with prospective randomized controlled
trials; compare to gold standard (laparoscopic cholecystectomy) and do better; best solutions may combine transluminal
and transabdominal instrumentation; surgeons and gastroenterologists should work together to solve problems
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| YOUR PERMANENT RECORD: HOW THE NATIONAL PRACTITIONER DATA BANK WORKS —Andrew Newton,
JD, Vice President for Legal Affairs, Medical College of Georgia, Augusta
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| National Practitioner Data Bank (NPDB): contains adverse information on health care practitioners; purpose to
provide nationwide flagging system to alert users to incompetent practitioners, prevent practitioners from avoiding discipline
and prevent state-skipping by practitioners with revoked licenses; started by Congress in 1986 but not operational
until September 1, 1990; lists many types of health professionals
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| Main categories: malpractice payments (any amount, even $1; refunding fees can count; waiving unpaid bill does not
count; payment must be based on written claim or suit); adverse actions against professional license, clinical privileges,
or membership in professional society (one with a formal peer review process); license revocation, suspension, probation,
or surrender; exclusion from Medicare or Medicaid; over half-million reports in databank
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| Mandatory reporting: malpractice payers, typically insurance company but can be hospital or group practice that self-
insures; practitioners do not have to report payments they make personally; licensure boards; professional societies
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| Access: restricted; hospitals and other health care entities with formal peer review; hiring requires consulting at hospitals
and nursing homes; state licensing boards; health care-related federal agencies, eg, Department of Justice; practitioner
can look at own data; plaintiff’s attorneys (access limited; must prove that sued entity did not query data bank)
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| Confidentiality: ensured; secure; information can be shared in peer review process
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| Adverse actions: based on professional competence or conduct that could adversely affect patient; professional competence
can include nonclinical issues, eg, sexual harassment; suspensions and limitations of medical staff privileges generally
not reportable unless >30 days; resignation in face of potential adverse action must be reported; reprimands not
reportable; voluntary leaves of absence for treatment of impairment usually not reportable
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| Disputing reports: before anyone sends report on physician into data bank, they must notify physician and give physician
opportunity to discuss; practitioner may enter explanation or rebuttal and can dispute report (based on factual errors)
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| Some statistics: 70% of 19,000 reports filed in 2003 involved malpractice, and 80% of these involved physicians; 4.6-yr
mean delay between incident and filing of report; >50% of hospitals have never filed report on physician
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| Significance of report: NPDB guidebook states that payment of claim does mean malpractice occurred; single report
usually not problematic for physician
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| Healthcare Integrity and Protection Data Bank: similar national database with health care-related criminal convictions
and civil actions; captures information from governmental actions, eg, involving physicians employed by Department
of Veterans Affairs
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| Other sources of information: physician should perform Web search on self and partners; licensing boards; private
background checks; managed care panels; patient-run Web sites and blogs; NPDB availeble at www.npdb-hipdb.com
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Educational Objectives
| The goal of this program is to educate the listener about advances in probiotics, transgastric and transcolonic surgery, and
the National Practitioner Data Bank (NPDB). After hearing and assimilating this program, the clinician will be better able
to:
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| 1. Describe chief characteristics of probiotics and their scientific therapeutic mechanisms.
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| 2. Discuss gastrointestinal conditions that currently benefit from use of probiotics.
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| 3. Review the technologic advances that have enabled development of transgastric and transcolonic surgical procedures.
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| 4. Cite some successful transgastric and transcolonic surgical procedures.
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| 5. Describe the NPDB and the types of reports it contains.
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Discussed on This Program
Metronidazole [Flagyl, Flagyl 375, Flagyl ER, Flagyl IV, Flagyl IV RTU, Metric 21, MetroCream, MetroGel, MetroGel-
Vaginal, MetroLotion, Noritate, Protostat]
Vancomycin [Vancocin, Vancoled]
Suggested Reading
Akerlund JE et al: Pouchitis. Curr Opin Gastroenterol 20:341.2004; Bartholomew LA: Quality of care and the National
Practitioner Data Bank: are the two related? J Med Pract Manage 15:64, 1999; Bengmark S et al: Prebiotics and
synbiotics in clinical medicine. Nutr Clin Pract 20:244, 2005; Floch MH et al: Recommendations for probiotic use. J
Clin Gastroenterol 40:275, 2006; Goossens DA et al: The effect of a probiotic drink with Lactobacillus plantarum 299v
on the bacterial composition in faeces and mucosal biopsies of rectum and ascending colon. Aliment Pharmacol Ther
23:255, 2006; Hurlstone DP et al: A prospective analysis of extended endoscopic mucosal resection for large rectal villous
adenomas: an alternative technique to transanal endoscopic microsurgery. Colorectal Dis 7:339, 2005; Jenkins B et
al: Probiotics: a practical review of their role in specific clinical scenarios. Nutr Clin Pract 20:262, 2005; Lamade W et
al: Transgastric surgery: avoiding pitfalls in the development of a new technique. Gastrointest Endosc 63:698, 2006; Lehrman
TD: Reconsidering medical malpractice reform: the case for arbitration and transparency in non-emergent contexts.
J Health Law 36:475, 2003; Mori T et al: Laparoscopic pancreatic surgery. J Hepatobiliary Pancreat Surg 12:451,
2005; Pugliese R et al: Laparoscopic splenectomy: A retrospective review of 75 cases. Int Surg 91:82, 2006; Rastall
RA: Bacteria in the gut: friends and foes and how to alter the balance. J Nutr 134:2022S, 2004; Schmidt H et al: Nutraceuticals
in critical care nutrition. Nestle Nutr Workshop Ser Clin Perform Programme: 245, 2003; Schmidt H et al: The
gastrointestinal tract in critical illness: nutritional implications. Curr Opin Clin Nutr Metab Care 6:587, 2003; Sclabas
GM et al: Endoluminal methods for gastrotomy closure in natural orifice transenteric surgery (NOTES). Surg Innov
13:23, 2006; Suggested Reading Waters TM et al: How useful is the information provided by the National Practitioner
Data Bank? Jt Comm J Qual Saf 29:416, 2003; Zocco MA et al: Efficacy of Lactobacillus GG in maintaining remission
of ulcerative colitis. Aliment Pharmacol Ther 23:1567, 2006
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Drs. Martindale, MacFayden and Newton were recorded at the Medical and Surgical Approaches to GI Disorders, presented
July 25-29, 2005, in Amelia Island, FL, by the Medical College of Georgia (www.mcg.edu/ce). The Audio-Digest
Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.
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