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BASF Pharma, SMG/Pankreas
Consensus
Conference
on the Management
of Cystic Fibrosis
Paris, June 3rd, 1994
With 18 Figures
Springer
Springer-Verlag GmbH & Co. KG
Science Communication
Editing Dept. for Medicine
Priv.-Doz. Dr. B. Fruhstorfer, Dr. A. Heinz,
D. Berger, U. Hilpert, K. Kupfer, Heidelberg
Coedited by Dr. Drev R. Chadha, Wassenaar
ISBN-13:978-3-540-58766-8 e-ISBN-13:978-3-642-79444-5
ISBN: 10.1007/978-3-642-79444-5
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Mailing Addresses of the Participants
Prof. Dr. M. Antonelli Prof. Dr. G. Lenoir
Cystic Fibrosis Center Necker-Enfants
Departmentof Pediatrics Malades Hospital
University of Rome Clinique Robert Debre
.,La Sapienza" 149, Rue de Sevres
Viale Regina Elena 324 75015 Paris
J0161 Rome France
Italy
Dr. J. Littlewood
Prof. Dr. N. Brousse Cystic Fibrosis Unit
Necker-Enfants St. James University
fyjalades Hospital Hospital Trust
Service Hematologie Beckett Street
149, Rue de Sevres Leeds LS9 7TF
75015 Paris UK
France
Prof. Dr. J.D. Lloyd-Still
Prof. Dr. J.A. Dodge Cystic Fibrosis Center
The Queen's Children's Memorial Hospital
University of Belfast 2300 Children's Parkway
Grosvenor Road Chicago IL 60614
Belfast BT12 6BJ USA
Northern Ireland
PD Dr. med. H.-G. Posselt
Prof. Dr. R. Fink Klinikum der Johann Wolfgang
Department Goethe-Universitat
~f Pulmonary Medicine Theodor-Stern-Kai 7
Children's National 60596 Frankfurt
fyjedical Center
11 Michigan Avenue N.W.
Washington, D.C. 20010 Dr. L. Romano
USA Department of Pediatrics and
CF Center
G. Gaslini Institute
Largo Gaslini, 5
16147 Genova
Italy
Dr. R.1. Smyth Dr. c.J. Taylor
Royal Liverpool Department of Pediatrics
Children's Hospital University of Sheffield
Alder Hey Sheffield S1 0 2TH
Liverpool L 12 2AP UK
UK
Contents
Opening Remarks
J.A. Dodge, Belfast .................................................. .
Presentation on the Questionnaire in CF Centres
in Germany
H.-G. Posselt, Frankfurt ............................................ 3
The Management of Cystic Fibrosis With Enzymes
in France
G. Lenoir, C. Silly, N. Brousse, J. P. Cezard,
and J. Navarro, Paris ................................................. 7
Pathology of Colonic Cystic Fibrosis Obstructions
c.
N. Brousse, J. Fournet, C. Silly, and G. Lenoir, Paris.. 13
One Year Monitoring of a Lipase Rich Pancreatic
Enzyme Preparation (Enzipan®) in the Treatment of
Severe Lipid Maldigestion of Cystic Fibrosis
M. Antonelli, S. Bertasi, M. Matrunola, and
P.Canuzzi,Rome..................................................... 19
Experiences from the CF Centre in Leeds, U.K.
J.M. Littlewood, St. James, Leeds .............................. 29
Chicago Experience of Intestinal Strictures
and Inflammatory Bowel Disease
J. D. Lloyd-Still, Chicago ........................................... 37
Pancreatic Enzymes Supplements: Administration
Guidelines at Genoa (Italy) CF Centre
L. Romano and C. Romano, Genoa........................... 41
Short Communications
L. Romano, c.J. Taylor, R.I. Smyth and R. Fink ......... 49
Discussion ................................................................ 53
I
Opening Remarks
J.A. Dodge, Belfast
The purpose of this meeting is to see what consensus there is
about how we use pancreatic enzymes in cystic fibrosis. En
zyme preparations have been available for many years, and
they have improved perhaps to the point where their effective
ness and dosage possibilities have gone ahead of our clinical
understanding. Inevitably it was knowledge that colonic stric
tures had occurred in some children who were taking pan
creatic enzymes, and the suggestion of a possible link
between the two, that has brought this whole issue to our at
tention. So we meet today with the object of exploring how
enzyme preparations are used in different European countries.
Our discussion will be informed by a knowledge of possible
complications but will not revolve around that.
It is very interesting to compare the attitudes and the regulato
ry managements of different countries. In the US pancreatic
enzymes are regarded not as drugs, but as digestive aids, and
until recently they did not need Food and Drug Administration
approval. In other countries, however, they are treated as
pharmacological agents. In reality the view that they are sim
ply natural products that relate to digestion is probably not
more tenable than saying that digoxin is simply digitalis leaf
that has been packaged. The concentration and purification of
pancreatic enzymes has been improved greatly, but still they
are a very crude biological substance. The potential variability
of the product, which makes it quite distinct from many drugs
which can be precisely measured and dosed and will be
totally consistent from one batch to another, is perhaps an
other area for discussion.
How do we handle these substances? We now have the tech
nology to make them very potent, but perhaps we do not yet -
at least for the high-strength products -have the experience to
know their proper place in the management of patients.
Now it gives me pleasure to ask my Co-Chairman to present
the results of a questionnaire which he has coordinated for the
CF centres in Germany.
Presentation on the Questionnaire
in CF Centres in Gernlany
H.-G. Posse It, Frankfurt
We have about 260 CF patients under regular care in Frank
furt. Soon after the first publication in The Lancet we sent a
questionnaire to the German CF centres with the following
questions:
1. How many CF patients have you cared for on a regular
basis ince 1985 (including tho e who died)?
2. How many of the patients were treated with pan reat
i enLyme u h a Creon 25 000 or Panzytrat 20 000 or
40000?
3. How many epi ode of distal intestinal obstru tion syn
drome (01 5) requiring pe ial Irealm nt did you ob
serve in the e patient ?
4. How many of the 0105 pati nt needed urgical inter
vention?
5. How many of th operated 0105 patient underwenl
bowel re ection?
6. In how many a e of the op rated palient wa the r -
e I d pe im n available for furth r inv tigati n?
7. How many patienl in your are r quir d laparotomy
bccaus of int tinal tri lure (ex luding n onat )?
Results of a questionnaire -German CF centres
o umb r of Germany CF centre qu tionnaire
ntto 71
o umb r of an w rs available for evaluation 60
o Total number of treated patients in the e centre 3205
o An wer available for pati nt treated with
high-lipa e preparation (%) 57
o Answer available for analy i of the individual (%) 54
o umb r of patient with 0105 requiring
pe ific m di ation 219
o umb r of pati nt with 01 5 r quiring
urgi al intervention 11
o Number of operated patient needing inte tinal
rese tion 4
o umb r of patient with inte tinal re e tion
caus d by indications other than 01 5 4
o umb r of re ected sp cim n available for
furth r hi topathologi al evaluation 7
PantreilliL C:!llIyme ~\lPI)lemelll,lIion do~al\ -regim n .waililble:
n =2782 palicnl~. LiIl.l<;C unilslkg body w>ightldie
cr nlr npalient % palienls 0 <5000 5000 10000 20000 <50000
\ ilh III -10000 20000 -50000
pr I).
(,0 3105 1619 100 1)19 922 623 175 23
52.4% 1.6'}h U.Il% 3 .1% 12.4% (,.1% 0.11%
Range of individual do age in Ihe 0 1.% 5.5% 3.0% 0 ()
different out pallen~ deplS. 10 10 10 10 10 10
10,4% 94% 88.2% 97% 50% 7.1%
Fig. 1. Colonic stric Seven histopathological specimens is a very small number
tures in CF-Results and I think it is a big problem that we have no knowledge of
of questionnaire III
normal intestinal histopathology in CF patients. The most im
- German CF
portant thing at the present time is that no patient was detect
Centres
ed with strictures of the intestine needing surgical treatment.
To the next part of the questionnaire, how is pancreatic en
zyme supplementation practised in the CF centres in Germa
ny? We have answers from 60 centres, with 3205 patients
under regular care. We have exact data about the individual
dosage for only 2782 patients. We grouped patients accord
ing to the supplementation they received: none, up to 5000,
5000-10000, 10000-20 ODD, 20000-50 ODD, and more than
50000 units lipase/kg body weight/day.
As seen in Fig.1 only 7% were on dosages above 20 000 units
lipase/kg body weight. However, there are very big differ
ences between the different centres in specific dosages. The
data from the Frankfurt centre from 251 patients are shown in
Fig.2.
Surprisingly, the patients on the higher dosages are the youn
ger ones. I think there is no good explanation why the smaller
Fig. 2. Pancreatic en
zyme supplementation 00,------------------------------------,
in CF (Outpatients, n =2 51 pallents
Frankfurt am Main,
50
1994)
f! 40 .,.
co '\._
~ 30 • Jl>... ~ ... , -· :\
.5: r.#a •• , -••
§> -". 'L-.:.-. ~<.-·" . .
20 OM~iti -' , '"'... .=.-- , ..••.• ,•-• --: .
.~ 7.. ..; ,. .. ~I t •• '.' ... -..
10 ; e •• ;,. r. e ":. ""
O;-----~----r---~----_r----,_----~--_4
o sooo 10000 15000 20000 25000 30000 35000
batients have this high dosage, and we need to clarify this. We
have to check whether the parents increase the dosage be
cause the stool appearance was not satisfactory.
Patients who developed strictures were taking very high dos
es. Many were taking more than 20000 units/kg body weight
daily. In Germany we use lower doses of lipase, and this might
be why we have had no patients with strictures.
