2. HINT OF HISTORY
Cruveilhier-1849- first described colonic
involvement by diverticular disease.
Term “ diverticulosis” – first used in 1914.
Acute diverticulitis recognized at the turn of the
20th century (due to” excess of roughage”!).
Burkitt &Painter-geografic distribution of the
condition (Western vs.Third world)-due to
industrialization of milling of FLOUR.
Diverticulosis is a DEFICIENCY disease!!
3. COLON DIVERTICULOSIS
NEW ASPECTS OF AN OLD DISEASE
Disease of age:30%<50y, 66%>85 y-on
P.M.studies.
m=f, at the beginning of 20th century m>f.
Western countries~35%,left sided
Eastern~4%,rt.sided.
Unheard before1900- with introduction of milling
of the flour which removes 2/3 of fiber content.
In USA crude fiber intake felt by 30% from
1900→1975.
4. NUMBERS AND
PATHOPHYSYOLOGY
Up to 5%, life long, will develop
complications, if by symptoms-up to 25%.
2%, life long, will need hospitalisation-50%
of those will require surgery.
30%-persistence of symptoms or recurrent
diverticulitis in 5y after first attack.
5. NUMBERS AND PATHOPHYSIOLOGY
Colonic wall-Circular muscle & 3 bands of longitudinal tenia coli.
“Pseudo diverticula”-weakest point at blood vessel entry on mesenteric site-
herniation of mucosa+ submucosa through muscularis to serosa.
Increased intraluminal pressure>120mm Hg: less fibers-less volume, more
constipation -higher pressure by LaPlace law→outporcketing.
Sigmoid has the smallest diameter-more diverticuli.
Lack of physical activity in elderly-independent factor for DD.
Elastin deposition in DD in tenia is 200% more than in normals.
Low fecal bile acid output –in DD.
In DD-symptomatic uncomplicated- 24 h colon motility studies show
increased duration of regular phasic patern -30%vs 6% in normal.
Low fiber diet results in micro-ecology changes -anaerobic /aerobics
bacteria, change in immune response, low grade inflammation, relative
ischemia of diverticular segment.
26. CONSERVATIVE THERAPY 2
Acute attack:
No change in the policy: I.V. fluids ,NPO,IV antibiotic
combination for aerobic & anaerobic flora, no difference
between the type of antibiot.
Duration- from 3-7 days ,than gradually restore PO intake
& therapy.
Low mortality -0-5 %, high recurrence 7-42%.yearly risk of
recurrence 3 %.
CHANGE: Increasing use of a new unabsorbable
antibiotic – Rifaximin in combination with Mesalazine.
27. CONSERVATIVE OUTPATIENT MANAGEMENT
OF ACUTE DIVERTICULITIS 3
Mizuki 2005,open,70pat,48 y(1997-2002).
Mild to moderate acute DD :clinical signs + lab + US –Gr.1a-c. Gr c-
peridiverticular abscess<2 cm.Gr 2- >2 cm with perforation
10days protocol: 3 days-1500ml sports drink+ free water+ oral
cephalosporin.-on 4th day-clear liquid +on 7th day liquid diet. Clinical
+ lab FU every 3 days. US on 4thd.
61pat-rt.sided DD. 68pat completed ,follow up 31 mo: 24%-recurrence,
majority in the same location, majority repeated the protocol.
Cost-343 $ vs 2018 $ -conventional . US is not good for obese patients
and in excess of gas .
Rt. Sided diverticulosis has a benign course-relevance to our
population??
30. FIBERS 2
Whole gut transit is twice slower in West than in Africans
(fibers?).
Transit time in IBS and Diverticulosis is faster than in
normal (so uncoordinated colonic activity is the problem
and not the transit).
Maternal diet- animal model (rat)- has significant
influence on offspring- depends on fiber rich or
deficient diet before conception.
Age dependence- declining strength of the collagen due
to increase of cross-linking of collagen produced in
elderly and fiber deficient patients.
31. FIBERS 3
Fiber rich diet does NOT reverse diverticulosis.
First RCT in 1976 by Brodribb & Humphrey-on 18 pats-significant
symptomatic relief on fibers vs. normal diet.
Gear-1979-Vegetarians, asymptomatic : use 42g/d(V)-vs.21g/d(N) : 2%m+0%f (V)
vs.31%m+ 21%f(N)-develops diverticulosis.
Hyland & Taylor-1980-100pts-6Y-after complicated dis.-91%remained symptom free
on H.F. diet.
Omstein1981-76 pts -4 mo.-bran7g/d vs.ispaghula 9g/d vs.placebo -lower abdominal
symptom score,straining,soften the stool ,increase stool weight and frequency.
Leahy-1985: 72 pats-retrospective-fewer complications & need for surgery.
Aldoory-1998 -43881 pts-Type of fiber plays a role too: insoluble fibers mainly
cellulose are the best in prevention of diverticular development!
34. RIFAXIMIN-New Kid On the Block1
Semi synthetic rifamycin deriv.-inhibits bacter.
RNA synthesis.-gram +,less for gram ,less for
bacteroids, unabsorbed.
Trials
Papi -1992 open,multicenter-217pts -
symptomatic uncomplicated DD:rif.800mg/d
vs. rif+ glucomannan 2 gr/d-7d /mo.for 12
mo:58% symp. free on combined therapy
vs.24%.+symptom score reduction: 64% vs.
48%. No side effects .DD complications-
0,9%vs2,7%.
35. RIFAXIMIN-New Kid On the Block2
Latella-2003, open: 968pts-symptomatic DD-glucomannan
4gr/d+rif.800mg vs.fiber only for 7d/mo. For 12 mo:56,5%-
combination group vs.29%-symptom free.No side effects. DD
complications- 1,3% vs 3,2%.
Papi-1995,randomised-168 pt.s-symptomatic uncomplicated DD:2gr
fiber+ 800mg rif.vs fiber + placebo for7d/mo for 12 mo.:69% in
combination vs.40%-were asymptomatic. No side effects . No
difference in DD complication rate.
CONCLUSION
Intermittent long term therapy with Rifaximin provides 30%
benefit over fibers alone.
QUESTION
Does it really prevent recurrence and complications on the
long run? (Baseline risk of complication in DD is 5 %/y).
37. MESALAZINE
OLD DRUG IN A NEW PLAY1
Di Mario, 2005, random. multicenter: 170pts
(67y mean age): R1-rif. 400mg/d ; R2-rif.
800mg/d; M1-mes. 800mg/d; M2
mes.1600mg/d-for 10 d/mo. For 3 months.
(symptom score of 11).
In all groups but R1-3/11 symptoms improved.
M2 – had the best results in symptom score
reduction.
38. MESAALZINE
OLD DRUG IN A NEW PLAY 2
Tursi,2002,218pts (65y) GrA-rif.800mg/d+
mes.2,4 gr/d 7 days, follow-800
mg+1600mg for 7d/mo .Gr B -rif. 800mg/d
7 days follow 800mg/7d/mo for 12 mo.
Significant symptom improvement in Gr A
vs. Gr B.
Acute DD recurrence-3 vs 13 pat (p<0.005).
39. MESALAZINE
OLD DRUG IN A NEW PLAY 3
Brandimarte 2004,open,90pts,67y with acute
symptomatic uncomplicated DD, outpatients.
rif.800mg+ mes.2,4 mg-for 10 days follow by
mis.1,6 g/d for 8 weeks-total symptom score
decreased from 1439-to 44 (p<0.001).
2 %-recurrent diverticulitis on misalazine alone
phase.
Side effects-4,4%-diarrhea on mesalzine+ 2%
pruritus + epigastric pain.
40. MESAALZINE
OLD DRUG IN A NEW PLAY 4
Conclusion
Mesalazine- based therapy is more effective
than rifaximin based therapy in treating
symptomatic DD + prevention of
exacerbation.
42. PROBIOTICS
Fric 2003 first published trial, open:15 mildly
symptomatic uncomplicaed DD outpatients,75y:
1 w antibiotics+2tab of E.Coli Nissle for 5w
average ,FU for 8-40 mo.
Previous 2 attacks with standard Rx –remission
lasted 2,4 mo. After probiotics-14,1 mo
(p<0.001).
Symptom score:1,84→0,21(p<0,001).
No controls , not randomized.
43. CALCIUM CHANNEL BLOCKERS
Morris 2003 - CCB vs Antimuscarinics in
protection against perforated DD.
Retrospect. Hospital charges for 5 y –serves
750000 popul. (NORFOLK,UK.).
Oral intake of CCB and antimuscarinic
immediately before the perforation.
120 pts+ 240 X2 matched controls (cataracts
and BBC).
Protective effect of CCB and not
antimiscarinic:OR: 0,4
44. LONG-TERM OUTCOME OF CONSERVATIVE
THERAPY FOR DIVERTICULITIS
Mueller, Munich, 2004,prospective ,252 pts, 7+13y FU.
Conservatively treated during 1985-1991,64y-interwed
in 1996+2002.
1FU-85 died-1from DD.53%asymptomatic+ 47%
symptomatic10 % readmission+ 8 % surgery.
2FU-only 55% could be reached(45%lost for FU), 37%-
recurrent symptoms.20%readmission,14%-surgery.
conclusions
High recurrence rate-34%,low mortality-0,8%,surgery-
10% should be left for relief of symptoms
rather than prevent death from complications.
45. POSSIBLE FUTURE TRENDS IN
THERAPY
*Probiotics with or without Mesalazine –for mild to
moderate uncomplicated attack.
*New antibiotic-Rifaximin plus Mesalazine for acute
uncomplicated attack.
*Surgery for complications.
*For chronic prevention (painful diverticulosis without
inflammation)-fiber+/-5ASA?other?
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*WE ARE WITNESS TO AN ACTIVE EVOLUTION OF
COMPLETELY NEW THERAPY IN DD.
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* MORE PROMISSING APROACHES STILL TO COME!!
