1. health and fitness
2. disease

Management
of Diverticular
Disease:
New Strategies,
New Approaches
March 10, 2012
10:00 AM – 11:15 AM
Houston, Texas
Educational Partner
Session 2: Management of Diverticular Disease: New Strategies, New Approaches
Learning Objectives
1.
2.
3.
4.
Characterize the patterns of prevalence and risk factors for diverticular disease.
Integrate evidence-based diagnostic approaches into the evaluation of patients with diverticular disease.
Formulate and apply appropriate medical management strategies when indicated for the treatment and prevention of
diverticulitis.
Incorporate patient counseling approaches regarding indications for elective surgical intervention.
Faculty
Sita S. Chokhavatia, MD
Associate Professor of Medicine
Division of Gastroenterology
Mount Sinai School of Medicine
New York, New York
Dr Sita Chokhavatia is associate professor of medicine in the Division of Gastroenterology at Mount Sinai School of Medicine in
New York City. She earned her medical degree from Seth G. S. Medical College at the University of Bombay, now the University
of Mumbai, India. Residency and fellowship followed at the Jersey City Medical Center in New Jersey.
Board certified in internal medicine, gastroenterology, and geriatric medicine, Dr Chokhavatia maintains clinical and research
interests in geriatric gastroenterology, irritable bowel syndrome (IBS), gastrointestinal dysmotility, gastroesophageal reflux disease,
and chronic constipation, with a special emphasis on the overlap of IBS with other organic gastrointestinal diseases.
Dr Chokhavatia is a member of and has been elected to fellowship in several discipline-related societies, among them the
American College of Physicians, the American College of Gastroenterology, the American Gastroenterological Society, and the
American Society of Gastrointestinal Endoscopy.
Martin H. Floch, MD, MACG, FACP, AGAF
Clinical Professor of Medicine
Digestive Disease Section
Yale University School of Medicine
New Haven, Connecticut
Dr Martin Floch is clinical professor of medicine at Yale University School of Medicine in New Haven, Connecticut, where he is
responsible for continuing medical education in gastroenterology and is involved in probiotic research in inflammatory bowel
disease and irritable bowel syndrome. He received his medical degree from New York Medical College in Valhalla; completed his
residency at Beth Israel Hospital in New York City; and trained in gastroenterology at the former Seton Hall College of Medicine
in South Orange, New Jersey.
From 1970 to 1994, Dr Floch was chairman of internal medicine at Connecticut’s Norwalk Hospital, where he was also founding
chief of gastroenterology and nutrition. A Master of the American College of Gastroenterology and a Fellow of the American
College of Physicians, Dr Floch has been awarded numerous National Institutes of Health grants at both Yale University and
Norwalk Hospital.
Dr Floch is editor of Netter’s Gastroenterology and co-author of Probiotics: A Clinical Guide. He is also editor-in-chief of the Journal of
Clinical Gastroenterology.
Session 2
Faculty Financial Disclosure Statements
The presenting faculty reported the following:
Dr Chokhavatia has no financial relationships to disclose.
Dr Floch has received a grant subsidy from Shire for his role as principal investigator.
Education Partner Financial Disclosure Statement
The content collaborators at Miller Medical Communications, LLC, report the following:
Lyerka D. Miller, PhD, has no financial relationships to disclose.
Suggested Reading List
Andeweg CS, Knobben L, Hendriks JC, et al. How to diagnose acute left-sided colonic diverticulitis: proposal for a clinical
scoring system. Ann Surg. 2011;253(5):940-946.
Chapman JR, Dozois EJ, Wolff BG, et al. Diverticulitis: a progressive disease? Do multiple recurrences predict less favorable
outcomes? Ann Surg. 2006;243(6):876-880; discussion 881-883.
Commane DM, Arasaradnam RP, Mills S, et al. Diet, ageing and genetic factors in the pathogenesis of diverticular disease. World J
Gastroenterol. 2009;15(20):2479-2488.
Hall J, Hammerich K, Roberts P. New paradigms in the management of diverticular disease. Curr Probl Surg. 2010;47(9):680-735.
Hall JF, Roberts PL, Ricciardi R, et al. Long-term follow-up after an initial episode of diverticulitis: what are the predictors of
recurrence? Dis Colon Rectum. 2011;54(3):283-288.
Jacobs DO. Clinical practice. Diverticulitis. N Engl J Med. 2007;357(20):2057-2066.
Lidor AO, Segal JB, Wu AW, et al. Older patients with diverticulitis have low recurrence rates and rarely need surgery. Surgery.
2011;150(2):146-153.
Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22(3):141-146.
O’Connor ES, Leverson G, Kennedy G, et al. The diagnosis of diverticulitis in outpatients: on what evidence? J Gastrointest Surg.
2010;14(2):303-308.
Rafferty J, Shellito P, Hyman NH, et al.; Standards Committee of American Society of Colon and Rectal Surgeons. Practice
parameters for sigmoid diverticulitis. Dis Colon Rectum. 2006;49(7):939-944.
Salzman H, Lillie D. Diverticular disease: diagnosis and treatment. Am Fam Physician. 2005;72(7):1229-1234.
Trivedi CD, Das KM; NDSG. Emerging therapies for diverticular disease of the colon. J Clin Gastroenterol. 2008;42(10):1145-1151.
Weizman AV, Nguyen GC. Diverticular disease: epidemiology and management. Can J Gastroenterol. 2011;25(7):385-389.
Zaidi E, Daly B. CT and clinical features of acute diverticulitis in an urban U.S. population: rising frequency in young, obese
adults. AJR Am J Roentgenol. 2006;187(3):689-694.
Session 2
Learning Objectives
Management of Diverticular Disease:
New Strategies, New Approaches
•
•
Sita S. Chokhavatia, MD, FACG, FACP, AGAF, FASGE
Associate Professor of Medicine
Division of Gastroenterology
Mount Sinai School of Medicine
New York, New York
•
Characterize the patterns of prevalence and risk
factors for diverticular disease
Integrate diagnostic approaches into the
evaluation of patients with diverticular disease
Formulate and apply appropriate medical
management strategies when indicated for the
treatment and prevention of diverticulitis
Martin H. Floch, MD, MACG, AGAF, FACP
Clinical Professor of Medicine
Digestive Disease Section
Yale University School of Medicine
New Haven, Connecticut
Pre-?
Drug List
Generic
dicyclomine
hyoscyamine
nifaximin
mesalamine
Trade
Bentyl
Byclormize
Dibeut
Di-Spaz
Dilomine
Levsin
Levsinex
Anaspaz
Cytospaz
Levbid
and others
Xifaxan
Pentasa
Lialda
Apriso
Asacol
Canasa
and others
How would you rate your level of knowledge
of diverticular disease?
1.
2.
3.
4.
5.
Expert
Very knowledgeable
Knowledgeable
Somewhat knowledgeable
Not at all knowledgeable
Pre-?
Pre-?
In which age group is diverticulitis more
prevalent in men than in women?
1.
2.
3.
What dietary changes would you recommend in
a patient with diverticular disease?
<50 years of age
50-75 years of age
>75 years of age
1.
2.
3.
4.
5.
1
Increase dietary fiber
Reduce refined carbohydrates
Avoid nuts
1 and 2 only
All of the above
Pre-?
The most common clinical presentation of acute
diverticulitis in the Western world includes:
Acute Diverticulitis
Epidemiology, Pathogenesis, Clinical Features
1.
2.
3.
4.
Left lower quadrant pain, elevated
white blood count, and rectal bleeding
Left lower quadrant pain, elevated
white blood count, and no rectal
bleeding
Right lower quadrant pain, fever, and
rectal bleeding
Right lower quadrant pain, fever, and
no rectal bleeding
Sita S. Chokhavatia, MD, FACG, FACP, AGAF, FASGE
Associate Professor of Medicine
Division of Gastroenterology
Mount Sinai School of Medicine
New York, New York
Diverticulosis Coli
Colonic Diverticulosis
¾
¾
¾
¾
¾
¾
Acquired disease of the Western world, industrial revolution
18th century: initial report
19th century: infection and inflammation of diverticula
20th century, early: first surgery description
20th century, latter part: increasing worldwide prevalence
21st century: economic burden, aging population and a frame
shift to younger age
Bogardus ST Jr. J Clin Gastroenterol. 2006;40 suppl 3:S108-S111; Hall J et al. Curr Probl Surg.
2010;47(9):680-735.
Variability in Disease Location by
Geographical Region
Diverticular Disease is Global
¾
Developed/ Western world:
z
z
z
¾
Prevalence: 5% to 45%
90% distal colon
Only 1.5% solely right colon diverticulosis
Africa and Asia:
z
z
z
Predominantly right colon: 70%-74%, especially ascending colon
Diverticulitis less common in Asians, increase in Africans adopting
Westernized diets
Japan: despite Westernization of diet, higher prevalence of rightsided disease, some increase in left colon diverticula
Nakada I et al. Dis Colon Rectum. 1995;38(7):755-759; Hall J et al. Curr Probl Surg. 2010;47(9):680-735.
2
Changing Trend in Diverticular Disease
Epidemiology of Diverticulosis Coli
Prevalence by age:
¾ < 40: 10%
¾ > 60: 30%
¾ > 80: 50%-70%
10% to 25% will develop diverticulitis unrelated to size,
number, extent; 80% of diverticulitis in patients >50 yrs
Prevalence by sex:
¾ Age <50: more common in males
¾ Age 50-70: slight preponderance in women
¾ Age >70: more common in women
NIS: sharpest increase for Northeast and Midwest USA
TTUHSC: increase in Hispanic males <40 years
Etzioni DA et al. Ann Surg. 2009;249(2):210-217; Nguyen GC et al. World J Gastroenterol. 2011;17(12):
1600-1605; Kijsirichareanchai et al. Am J Gastroenterol. 2011;106(2):A401
Jacobs DO. N Engl J Med. 2007;357(20):2057-2066.
Diverticulosis
Diverticular Disease
¾
Diverticulum:
Sac-like protrusion of mucosa and submucosa through the
muscular layer of the colonic wall
Diverticulosis: presence of diverticula within the colon,
incidental
Diverticulitis: inflammation of a diverticulum, perforation
¾
Occurs in weak areas of the bowel wall
Diverticular hemorrhage: bleeding diverticulum, no diverticulitis
¾
Typically 5–10 mm in size
¾
Single or multiple
¾
False diverticula - pseudodiverticula
Touzios JG et al. Gastroenterol Clin N Am. 2009;38(3):513-525; West AB et al. J Clin Gastroenterol.
2004;38(5 suppl 1):S11-S16; Bogardus ST Jr. J Clin Gastroenterol. 2006;40 suppl 3:S108-S111.
Risk Factors
Etiology: Multifactorial
¾
Anatomical/Structural
¾
Motility
¾
Fiber
¾
Other risk factors
¾
Age
¾
Physical inactivity
¾
Obesity
¾
Constipation
¾
Smoking, caffeine, alcohol consumption
¾
NSAIDs, opiates
Commane DM et al. World J Gastroenterol. 2009;15(20):2479-2488; Korzenik JR. J Clin Gastroenterol
2006;40 suppl 3:S112-S16; Aldoori WH et al. Ann Epidemiol. 1995;5(3):221-228.
3
Structural Factors
¾
Outer longitudinal layer – 3 taenia
¾
Intrinsic weakness at vasa recta entry site
¾
Increased collagen cross linkage, age-related increase
¾
Increased elastin deposition, genetic (Marfan/ED syndrome)
¾
Decreased compliance of thickened colon
¾
Increased intraluminal pressures
Colon Dysmotility
¾
Segmentation – simultaneous contraction of adjacent haustra
¾
Extremely high intraluminal pressure zone
¾
Hypermotility- non propulsive
¾
Delayed transit
¾
Altered chemical mediators
ED=Ehlers-Danlos
West AB et al. J Clin Gastroenterol. 2004;38(5 suppl 1):S11-S16; Hall J et al. Curr Probl Surg. 2010;
47(9):680-735; Wess TJ et al. Gut. 1995;37(1):91-94.
Bassotti G et al. Dis Colon Rectum. 2001;44(12):1814-1820; Matrana MR et al. Clin Colon Rectal Surg.
2009;22(3):141-146.
Diet, Fiber, and Diverticular Disease
Sigmoid has the smallest diameter and largest pressures
¾
Epidemiological data: strong inverse relationship (fruit,
vegetable, popcorn, nut, seed consumption)
¾
Low fiber→ less bulky stool →less water retained→ longer
transit: increased intracolonic pressure + altered micro flora
¾
Fiber-deficient diet (high in refined carbs):
z
z
Segmentation = exaggerated increase in intraluminal pressures
¾
Laplace’s law: T=rP
Tension in wall of hollow cylinder is proportional to its radius
multiplied by pressure within
Diet high in red meat and total fat content:
z
Clinical Spectrum
of Diverticular Disease
Asymptomatic
¾
Symptomatic
Uncomplicated diverticulitis
Recurrent symptomatic disease
Complicated disease
¾
increased risk of developing diverticular disease
Strate Ll et al. JAMA. 2008;300(8):907-914; Floch MH et al. J Clin Gastroenterol. 2005;39(5):355-356;
Hall J et al. Curr Probl Surg. 2010;47(9):680-735.
Kang JY et al. Drugs Aging. 2004;21(4):211-228.
¾
increased risk of developing diverticular disease
diverticular disease less common in vegetarians
Segmental Colitis Associated with
Diverticulosis
Special conditions:
Young patients, immuno-compromised patients, giant
diverticulum, right-sided diverticulitis, SCAD
¾
Symptoms overlap with IBD
¾
Older male patient
¾
Diarrhea
¾
Rectal bleed
Endoscopic features: rectal and proximal colon sparing,
inflammation restricted to segment with diverticulosis
¾ Seen in 0.25%-1.5% of colonoscopies
¾
SCAD=segmental colitis associated with diverticulosis
IBD=inflammatory bowel disease
Symeonidis N et al. Tech Coloproctol. 2011;15 suppl 1:S5-S8; Sachar DB; NDSG. J Clin Gastroenterol.
2008; 42(10):1154-1155; Hall J et al. Curr Probl Surg. 2010;47(9):680-735; Tursi A. Dig Dis Sci. 2011;
56(1):27-34.
Imperiali G et al. Am J Gastroenterol. 2000;95(4):1014-1016; Peppercorn MA. J Clin Gastroenterol.
2004;38(5 suppl 1):S8-S10; Harpaz N et al. J Clin Gastroenterol. 2006;40 suppl 3:S132-S135.
4
Symptomatic Uncomplicated
Diverticular Disease (SUDD)
Stages of Diverticular Disease (DD)
Stage I: development of diverticula
Stage II: asymptomatic DD
¾ Stage III: symptomatic uncomplicated DD
single episode acute diverticulitis
multiple discrete episodes of acute diverticulitis
smoldering symptoms
¾ Stage IV: complicated DD
abscess, fistula, perforation, obstruction, stricture,
purulent and fecal peritonitis, bleed
¾
¾
Hinchey diverticulitis classification Stage I- IV (surgical)
Floch MH; NDSG. J Clin Gastroenterol. 2008;42(10):1135-1136; Touzios JG et al. Gastroenterol Clin N Am.
2009;38(3):513-525.
¾
Symptoms overlap with IBS
¾
Chronic colicky/Constant lower abdominal pain
¾
Pain relieved with defecation, passage of flatus
¾
Bloating, distension, flatulence
¾
Associated alteration in bowel habit
¾
No signs of inflammation (fever, leukocytosis)
IBS=irritable bowel syndrome
Stages of Diverticular Disease
Mechanisms for Abdominal Symptoms
¾
Intestinal bacterial overgrowth
¾
Mucosal low-grade inflammation
¾
Abnormal activation of intrinsic and extrinsic primary
afferent neurons
¾
Neural and muscle dysfunction
¾
Visceral hypersensitivity
Stage I: development of diverticula
Stage II: asymptomatic DD
¾ Stage III: symptomatic uncomplicated DD
single episode acute diverticulitis
multiple discrete episodes of acute diverticulitis
smoldering symptoms
¾ Stage IV: complicated DD
abscess, fistula, perforation, obstruction, stricture,
purulent and fecal peritonitis, bleed
¾
¾
Hinchey diverticulitis classification Stage I- IV (surgical)
Simpson J et al. Br J Surg. 2003;90(8):899-908; Spiller R et al. J Clin Gastroenterol. 2006;
40 suppl 3: S117-S120.
Floch MH; NDSG. J Clin Gastroenterol. 2008;42(10):1135-1136; Touzios JG et al. Gastroenterol Clin N Am.
2009;38(3):513-525.
Fiber Deficiency Causes Diverticulitis?
What Causes Diverticulitis?
¾
Obstruction of diverticulum
¾
Stasis
¾
Altered bacterial microflora
¾
Local ischemia
¾
Ulceration
¾
Micro/Macro perforation
Fiber-deficient diet
Diverticula
Altered microflora
Altered immune response
Microscopic colitis
SCAD
Touzios JG et al. Gastroenterol Clin N Am. 2009;38(3):513-525; Hall J et al. Curr Probl Surg. 2010;47(9):
680-735; Heise CP. J Gastrointest Surg. 2008;12(8):1309-1311.
Floch MH et al. J Clin Gastroenterol. 2005;39(5):355-356.
5
Stages of Diverticular Disease
Acute Diverticulitis Symptoms
¾
¾
¾
¾
¾
¾
¾
¾
¾
Stage I: development of diverticula
Stage II: asymptomatic DD
¾ Stage III: symptomatic uncomplicated DD
single episode acute diverticulitis
multiple discrete episodes of acute diverticulitis
smoldering symptoms
¾ Stage IV: complicated DD
abscess, fistula, perforation, obstruction, stricture,
purulent and fecal peritonitis, bleed
¾
Left lower quadrant pain
Supra pubic/ RLQ pain
Fever
Anorexia
Nausea/ vomiting
Bloating
Altered bowel habit
Tenesmus
Urinary symptoms
¾
Hinchey diverticulitis classification Stage I- IV (surgical)
RLQ=right lower quadrant
Floch MH; NDSG. J Clin Gastroenterol. 2008;42(10):1135-1136; Touzios JG et al. Gastroenterol Clin N Am.
2009;38(3):513-525.
Clinical Features of Complicated Disease
Case: A 76 y/o Woman
Abscess/ Perforation
Purulent peritonitis
Fecal peritonitis
Colovesical fistula 65%
Pneumaturia
Fecaluria
Hematuria
Cystitis
Colovaginal fistula 25%
Vaginal discharge
¾ Intestinal obstruction, ileus
¾ Diverticular hemorrhage
¾ Extra intestinal manifestation
Presentation:
Intermittent chronic diffuse abdominal pain, bloating
Severe x 3 days; associated nausea, distension, no fever
¾
Physical Exam:
VSS, distended soft abd-no guarding/rebound, +BS, –FOBT
Labs:
Hgb: 11.6
WBC: 5.4;
Glucose: 160
HbA1c: 8.2
Creatinine: 0.7
Woods RJ et al. Dis Colon Rectum. 1988 Aug;31(8):591-6.
Growth of an Aging Population, USA
BS=bowel sounds
FOBT=fecal occult blood test
Hgb=hemoglobin
HbA1C=glycosolated hemoglobin
VSS=vital signs stable
WBC=white blood count
Presentation May Be Atypical!
¾
2005: 35 million >65yrs
155,000 >90yrs
Age-related physiologic changes AND comorbid
diseases AND polypharmacy:
¾
2020: 22% of population >65yrs
over 3 million >90yrs
¾
Normo/hypothermia and lower leukocyte counts in
severe infections; NSAIDs block inflammatory response
Effect of aging: disease presentation
response to Rx
iatrogenic complications
ethical and social issues
¾
¾
Normal blood pressure in hypertensive patient
reflects hypotension; no tachycardia if beta-blocker Rx
¾
No guarding/rigidity may be elicited as lax abdominal wall
¾
Delirium; opioids block pain and alter mental status
6
Case: A 25 y/o Man
Diverticular Disease in the Young
Presentation and History:
3 year h/o chronic constipation
1 day LLQ pain/ spasms, fever; no nausea, vomiting, BRBPR
1.5 pack/yr x 10 years, 4 beers/weekends, occasional marijuana
ER eval for similar symptoms 11 months ago and 6 months ago
1 sister has Crohn’s disease
ER evaluation:
• CT abdomen/pelvis- sigmoid wall thickening, diverticula,
adjacent inflammatory changes
• Normal labs
¾
2%-30% of all diverticular disease
¾
2%-5% male predominance
¾
Virulence debated
¾
Higher lifetime surgery rate
¾
Longer life expectancy = greater recurrences
Nguyen GC et al. World J Gastroenterol. 2011;17(12):1600-1605.
Diverticulitis
Advances and Dilemmas in Treatment
Martin H. Floch, MD, MACG, AGAF, FACP
Clinical Professor of Medicine
Digestive Disease Section
Yale University School of Medicine
New Haven, Connecticut
Clinical Picture
Antispasmodics
• Asymptomatic
• Symptomatic
• Dicyclomine HCl 10 or 20 mg – every 4-6 hours - up to
4 doses daily
– Uncomplicated
Stages 1, 2a
• Pain
• Change in bowel habit
– Complicated
Stages 2 a-h (above plus)
• Fever
• Elevated WBC
• Abdominal tender mass
• CT findings
• Possible Sx of fistula
• Hyoscyamine sulfate 0.125 mg – 1 to 2 doses every 4
hours as needed (there are extended-release forms)
These drugs are not FDA-approved for treatment of diverticular disease
7
Diet/Pathophysiology
Dietary Fiber
• Burkitt, Trowell and others correlate prevalence of
diverticula with low-fiber diets
• Data accepted as evidence that diverticular disease is
a fiber-deficiency disease
• High fiber intake used to treat increased spasm and
increased segmental contractions by British in 1970s
• Dietary Allowances now recommend 22-28 g of dietary
fiber as correct intake in women and 28 to 34 g in men
–varies with size
• But Western dietary fiber study reveals intake varies
between averages of 8-10 g in most
• In vegan diets as much as 40-50 g/day
• This is a deficiency disorder
• Treatment includes high (normal) fiber diet
Burkitt DP, Trowell HC, eds. Refined Carbohydrate Foods and Disease: Some Implications of Dietary Fibre.
Academic Press; 1975. Painter NS et al. Br Med J. 1971;2(5759):450-454; Ravikoff, J Clin Gastroenterol.
2011;45:S3. Pennington JA et al. Bowes and Church’s Food Values of Portions Commonly Used. Philadelphia,
PA: LWW; 2010; health.gov. 2010 Dietary Guidelines. www.dietaryguidelines.gov.
Pathophysiology
Dietary Fiber and Bacterial Flora
• Compared subjects on high bran diet to same subjects
on regular diet
• Flora definitely different
• Significant alteration in relationships of aerobes and
anaerobes, anaerobes inc.
• (Similar results in other studies comparing flora of
subjects on Western and Eastern diets)
• Conclusion: there is a dysbiosis in low-fiber diets
• Implications for diverticular disease patients
• No intestinal microbatome studies as yet with new
genetic rRNA polymerase techniques, but definite
changes with those methods in IBS and IBD
• Low-fiber diets have different colonic flora than highfiber diets
• Is there an alteration in the healthy protective bacteria?
Is there a dysbiosis?
• Decreased lactobacilli and bifidobacteria result in
lessened immunity and proliferation of harmful
organisms
• Diverticular disease patients have less fiber intake and
hence change in flora that possibly promotes disease
and inflammation
Fuchs H-M et al. Am J Clin Nutr. 1976;29(12):1443-1447.
Is There Evidence to Support Dietary
Modification?
Low-fiber diet
diverticula formation
Low-fiber diet
change flora
• Historically, low-fiber diets were recommended for diverticulitis
because of a concern that indigestible nuts, seeds, corn, and
popcorn could enter, block, or irritate a diverticulum, resulting in
diverticulitis and possibly increasing perforation risk
To date, there is NO evidence supporting such a practice
Change in flora
colitis
• Dietary fiber supplementation has been advocated to prevent
diverticula formation and recurrence of symptomatic diverticulosis
– Recommendations based largely on low-powered, epidemiologic
observational studies
Diverticulitis
Strate LL et al. JAMA. 2008;300(8):907-914.
8
Is There Evidence to Support Dietary
Modification?
Clinical Picture
• An 18-year study investigated the association of nut, corn, or
popcorn consumption with diverticulitis and diverticular bleeding
• Asymptomatic
• Symptomatic
• 47,228 men aged 40-75; free of diverticulosis or its complications,
cancer, and IBD at baseline; assessed via food-frequency
questionnaire
– Uncomplicated
Stages 1, 2a
• Pain
• Change in bowel habit
– Complicated
Stages 2 a-h (above plus)
• Fever
• Elevated WBC
• Abdominal tender mass
• CT findings
• Possible Sx of fistula
• During follow-up, inverse associations noted between nut and
popcorn consumption and the risk of diverticulitis
• Multivariate hazard ratios for men with highest intake of each food
vs men with lowest intake were 0.80 (P for trend = .04) for nuts
and 0.72 (P for trend = .007) for popcorn
In this large prospective study in men, nut, corn, and popcorn
consumption did not increase the risk of diverticulitis or diverticular
complications, but decreased the risk of diverticulosis
Strate LL et al. JAMA. 2008;300(8):907-914.
New Nonabsorbable Antibiotics
Standard Textbook Antibiotic Rx
•
•
•
•
•
In acute stages
For uncomplicated symptomatic disease
For microabscess
For abscess
For fistula
• In 3 RCT of 555 patients with symptomatic
uncomplicated disease rifaximin cyclic therapy of
400 mg bid for 7 d/mo significantly decreased
symptoms
• In open label study of 968 patients cyclic therapy
superior to high-fiber diet Rx
• Therefore, cyclic therapy is recommended
• Rx anaerobic and aerobic flora, po or iv
• Use quinolone/metronidazole, trimethoprimsulfamethoxazole, or amoxicillin/clavulinic acid
• Antibiotics used continuously from 1 to 4 weeks
• Recurrent use depends on symptoms and findings and
may herald surgical intervention
Rifaximin is not FDA approved for the treatment of diverticulitis.
RCT=randomized controlled trial
Trivedi CD et al; NDSG. J Clin Gastroenterol. 2008;42(10):1145-1151.
Salzman H et al. Am Fam Physician. 2005;72(7):1229-1234.
Other New Treatments
Mesalamine
Based on theory of chronic inflammation
• FDA-approved indication – ulcerative colitis
• Most common side effects: headache, abdominal pain,
diarrhea
• Mesalamine?
• Italy – Diverticulitis
• Probiotics?
Study
Treatment
Trespi (1999)
antib-7d/mes-8 wks,4 yr f/up
Tursi (2002)
rif/mes vs rif alone;12 mo
Tursi (2004)
rif/mes 10d-8 wks,8 wk f/up
Di Mario (2005)
rif 200 mg/rif 400 mg/mes 400 mg/mes 800 mg
• USA – Diverticulitis – Randomized controlled trials
- DIVA Trial
- PREVENT 1 and PREVENT 2
Trespi E et al. Minerva Gastroenterol Dietol [in Italian]. 1999;45(4):245-252. Tursi A et al. Dig
Liver Dis. 2002;34(7):510-515. Tursi A et al. Dig Dis Sci. 2007;52(3):671-674. Di Mario F et al.
Dig Dis Sci. 2005;50(3):581-586.
9
Mesalamine for Diverticulitis
Mesalamine in Diverticulitis: DIVA Study
• 170 patients, 98M, 72F, 67.1 yrs (39-84)
• Randomized comparison of mesalamine ± probiotics vs
placebo in patients with acute diverticulitis
• N = 117 patients with acute diverticulitis
• 4 arms:
1. rifaximin 200 mg bid
2. rifaximin 400 mg bid
3. mesalamine 400 mg bid
4. mesalamine 800 mg bid
• 3 arms:
1. Mesalamine 2.4 g
2. Mesalamine 2.4 g + B infantis (probiotic)
3. Placebo
• Treated 10 days per month for 3 months
• At 52 wks, 40.7% in mesalamine group reported
complete symptom response vs 18.2% in placebo group
• Studied global symptom score (GSS) – 11 sx
• All groups improved except rifaximin 200 mg
• Mesalamine did not decrease the rate of recurrent
diverticulitis
• Addition of probiotic did not affect outcomes
• Mesalamine-treated patients had lowest GSS
Stollman N et al. Presented at: American College of Gastroenterology annual meeting;
October 15-20, 2010; San Antonio, TX. Abstract.
Di Mario F et al. Dig Dis Sci. 2005;50(3):581-586.
Mesalamine in Diverticulitis: PREVENT 1
Study
Probiotics for Diverticulitis
• 6 studies in literature
• First study in 1993 – rifaximin 7d/mo. followed by
Lactobacillus sp 7d/mo for 12 mo in 79 pts.decreased symptoms and no acute attacks or
complications
• In 2003 – In 15 patients for 8-40 mo +
antibiotic+intestinal absorbent for one week + or –
E coli Nissle for 5 weeks = decreased symptoms and
no attack for 2.43 mo vs 14.1 mo (p<.001)in probiotic
Rx
• Randomized, prospective, double-blind study
investigating prevention of acute diverticulitis
• N = 584, 104 wks
• 4 arms:
1. Mesalamine 1.2 g/day
2. Mesalamine 2.4 g/day
3. Mesalamine 4.8 g/day
4. Placebo
• Results are pending
Giaccari S et al. Riv Eur Sci Med Farmacol. 1993;15(1):29-34; Fric P et al. Eur J Gastroenterol
Hepatol. 2003;15(3):313-315.
www.clinicaltrials.gov
Overview of Probiotics for Diverticulitis
Probiotic Study/
Year
Stage
N/
Follow-up
Outcome
L casei, 5-ASA, or both
2006
Symptomatic
uncomplicated
90
12 months
Increased
remission rate
L Casei + 5-ASA
2008
Symptomatic
uncomplicated
75
24 months
Increased
remission rate
VSL#3 + balsalazide
2007
Uncomplicated
30
12 months
Improved
symptoms
L Acidophilus +
L helveticus +
Bifidobacterium
2010
Symptomatic
uncomplicated
45
6 months
Prevented
recurrence,
improved
symptoms
Treatment
Usual Practice – No Established Guidelines
• Varies with Stage
• Uncomplicated Stage 1
– High (normal) fiber diet (HFD) with or without antispasmodics
and antibiotics (approved/standard therapy)
– Mesalamine – off label
– Probiotics – no controlled studies
• Complicated Stage 2 –
– varies from NPO, to liquid diets, to no-fiber diets,
to regular diet
– Antibiotics
– Antispasmodics
– Mesalamine – off label
– Probiotics – no controlled studies
In summary…
5 different probiotic protocols
tested in various stages
of diverticulitis
(no placebo-controlled studies)
With up to
40 months
follow-up in 334
patients
Have produced
suggestive but
inconclusive results
• Surgical Rx for complicated disease
• Prevent Recurrences
Tursi A et al. J Clin Gastroenterol. 2006;40(4):312-316; Tursi A et al. Hepatogastroenterology.
2008;55(84):916-920; Tursi A et al. Int J Colorectal Dis. 2007;22(9):1103-1108; Lamiki P et al.
J Gastrointestin Liver Dis. 2010;19(1):31-36.
Sheth AA. J Clin Gastroenterol. 2011;45(suppl 1):S43.
10
The Role of Surgery in Diverticulitis
Diverticulitis
Indications for surgery in acute diverticulitis
• Generalized peritonitis or free perforation, and patient is unstable
• Clear signs of obstruction not amenable to nonoperative measures
• Worsening clinical course after initial response
• What about recurrences?
Indications in recurrent diverticulitis
• Sigmoid colectomy no longer recommended after 2 episodes
• Elective resection should be considered on a case-by-case basis,
influenced by medical condition such as age, immune status, and
comorbidities
Strong SA. J Clin Gastroenterol. 2011;45(suppl 1):S62-S69; Beddy D et al. J Clin Gastroenterol.
2011;45(suppl 1):S74-S80.
Diverticular Disease:
Response and Recurrence
Natural History of Diverticular Disease
• Approximately 70% to 100% of patients respond to
medical treatment to resolve a first acute attack of
diverticulitis
• About 33% of patients will experience recurrent
diverticulitis – often within 1 year of the first episode
• The 5-year recurrence rate is 19% to 54%
• Traditionally, surgical intervention was recommended
after 2 or more episodes of acute, recurrent
diverticulitis
• Between 80% and 85% of patients with DD remain
asymptomatic
• Of the 15%-20% symptomatic patients:
– Approximately 75% will have painful DD without
inflammation
– Approximately 1%-2% will require hospitalization
– Approximately 0.5% will require surgery
Stollman N et al. Lancet. 2004;363(9409):631-639.
Tursi A et al. Aliment Pharmacol Ther. 2009;30(6):532-546.
Controversy Regarding Medical Versus
Surgical Management of Diverticulitis
Elective Surgery for the Treatment of
Acute Uncomplicated Diverticulitis
• Medical and surgical treatments have never been
compared in a randomized, controlled trial in patients
with diverticulitis
• Recurrent attacks occur in 33% of patients after
medical resolution of initial episode
– Is an antimicrobial approach only effective in the
short term?
– Data suggest that antibiotics may be no more
effective at preventing future symptomatic episodes
of mild uncomplicated diverticulitis than observation
combined with bowel rest
• In 1999 Practice Parameters of the ASCRS and EAES
recommended elective surgery
– After 2 episodes of uncomplicated acute
diverticulitis
– After 1 episode in young patients
• In 2006 the ASCRS recommended that elective
surgery should be made on an individual basis after a
favorable response to conservative treatment
ASCRS=American Society of Colon and Rectal Surgeons
EAES=European Association for Endoscopic Surgery
Stollman NH et al. Am J Gastroenterol. 1999;94(11):3110-3121; Kohler L et al. Surg Endosc.
1999;13(4):430-436; Rafferty J et al; Standards Committee of ASCRS. Dis Colon Rectum.
2006;49(7):939-944.
Tursi A et al. Dig Dis Sci. 2011;56(11):3112-3121; Hjern F et al. Scand J Gastroenterol.
2007;42(1):41-47.
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Recurrent Mild Diverticulitis
When To Consider Elective Surgery
for Acute Diverticulitis
• If no perforation, then each case treated based on
findings. Rule of surgery after 2 attacks no longer
exists and mild recurrent attacks do not have bad
prognosis
• However, perforation has increased 6x mortality rate
• Elderly and comorbidities increase mortality rate
• The number of attacks of uncomplicated
diverticulitis is not necessarily a determining factor
in defining the appropriateness of surgery
• CT graded severity of a first attack is a predictor of
an adverse natural history and may be helpful in
determining the need for surgery
• Elective colon resection advised if an episode of
complicated diverticulitis is treated nonsurgically
– After percutaneous drainage of a diverticular abscess, a later
colectomy usually should be planned, because 41% of
patients will otherwise develop severe recurrent sepsis
Humes DJ et al. Gastroenterology. 2009;136(4):1198-1205.
Rafferty J et al; Standards Committee of ASCRS. Dis Colon Rectum. 2006;49(7):939-944.
When To Consider Elective Surgery for
Acute Diverticulitis (cont’d)
Hinchey Grading System for Complications
Related to Perforated Acute DD
Stage
Hinchey Classification
I.
Pericolic abscess or
phlegmon
II.
Pelvic, intra-abdominal,
or retroperitoneal
abscess
Stage
I.
Hinchey Classification
Modified by Sher
• Consider elective surgery in patients:
– Who develop complications, such as fistulas,
obstruction, or nonresolving smoldering disease
Pericolic abscess
IIa.
Distant abscess amendable
to percutaneous drainage
IIb.
Complex abscess associated
with fistula
III.
Generalized purulent
peritonitis
III.
Generalized purulent peritonitis
IV.
Generalized fecal
peritonitis
IV.
Fecal peritonitis
– Who have had 2 or more episodes of severe
diverticulitis, as determined by their clinical
presentation and CT grade
– With limited access to medical care
– Who are concerned about the negative impact of
repeated illnesses with regard to work productivity
and/or psychosocial issues
The Hinchey classification is not applicable to the majority of
patients with diverticulitis who do not require surgery
Bordeianou L et al. J Gastrointest Surg. 2007;11(4):542-548.
Hinchey EJ et al. Adv Surg. 1978;12:85-109; Sher ME et al. Surg Endosc. 1997;11(3):264-267.
Laparoscopic Colectomy
What to Tell the Patient ?
• A laparoscopic colectomy is appropriate in selected
patients – advantages include:
– less pain
– smaller scar
– shorter recovery
• Asymptomatic:
– HFD – don’t worry, but if pain, need evaluation
– 75% to 90% remain asymptomatic
– 10% to 25% may develop symptoms, but only 1%-2% require
hospitalization
• Compared to open resection
– There is no increase in early or late complications
– A 27% reduction in major morbidity at 6 months
– Cost and outcome are comparable
• Elderly – need clinical observation if symptomatic
• Young – essentially no difference
• Laparoscopic surgery is acceptable in the elderly and
is safe in selected patients with complicated disease
Rafferty J et al; Standards Committee of ASCRS. Dis Colon Rectum. 2006;49(7):939-944;
Klarenbeek BR et al. Surg Endosc. 2011;25(4):1121-1126.
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Quality of Life (QOL) Issues in
Diverticular Disease
QOL Post Surgery for DD
• Mass General/Harvard evaluation of 325 patients
who had open or laparoscopic sigmoid resection with
restoration.(no control group/no preoperative bowel
sx)
• Survey from 2001 to 2008 (9 surgeons)
• 249 returned QOL evaluations
• 20% reported fecal incontinence (>in females),
urgency or incomplete evacuation. Prospective study
needed.
•
•
•
•
Prevalence >80% after age of 60
Only 10% to 25% develop symptoms
Complications in 5%-20% of symptomatic
Few QOL studies in symptomatic, but they indicate
DD has a negative effect
• Surgery needed in 0.5%
Angriman I et al. World J Gastroenterol. 2010;16(32):4013-4018; Comparato G et al. Dig Dis.
2007;25(3):252-259.
Levack MM et al. Dis Colon Rectum. 2012;55(1):10-17.
Post-?
Summary
• Diverticula appear to form due to deficient fiber intake associated
with increased or disturbed colonic motility.
• Low-fiber intake is also associated with a change in colonic flora.
A high fiber diet is recommended.
• Chronic low-grade inflammatory mucosal changes occur that may
progress to severe focal inflammation with complications of
abscess or perforation.
• Medical treatment depends on the stage of the disease, ranging
from treatment for uncomplicated symptomatic disease to disease
with complications and use of antibiotics.
• Investigational trials:
• Initial mesalamine studies indicate it may be effective in
improving symptoms and preventing recurrence.
• limited uncontrolled trials with probiotics have shown some
favorable results.
• Rifaximin has shown symptomatic improvement.
• Surgical intervention or resection is indicated on an individual
basis in complicated disease.
How would you rate your level of knowledge
of diverticular disease?
1.
2.
3.
4.
5.
Expert
Very knowledgeable
Knowledgeable
Somewhat knowledgeable
Not at all knowledgeable
Post-?
Post-?
In which age group is diverticulitis more
prevalent in men than in women?
1.
2.
3.
What dietary changes would you recommend
in a patient with diverticular disease?
<50 years of age
50-70 years of age
>75 years of age
1.
2.
3.
4.
5.
13
Increase dietary fiber
Reduce refined carbohydrates
Avoid nuts
1 and 2 only
All of the above
Post-?
The most common clinical presentation of acute
diverticulitis in the Western world includes:
1.
2.
3.
4.
Left lower quadrant pain, elevated
white blood count, and rectal bleeding
Left lower quadrant pain, elevated
white blood count, and no rectal
bleeding
Right lower quadrant pain, fever, and
rectal bleeding
Right lower quadrant pain, fever, and
no rectal bleeding
14