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SUMMARY of BIOMED 2 supported PROJECT BMH4-CT96-2383
“EUROFOETUS”
| Full title of proposal: |
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ENDOSCOPIC ACCESS TO THE FETO-PLACENTAL UNIT:
FROM EXPERIMENTAL TO CLINICAL APPLICATIONS |
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| Contract period: |
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1 October 1998 – 30 September 2001 |
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| Coordinator: |
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Katholieke Universiteit Leuven, Prof. Dr. Jan
Deprest |
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Dept. of Obstetrics and Gynaecology |
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University Hospitals Katholieke Universiteit Leuven |
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Herestraat 49 - B-3000 Leuven |
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Tel: +32 16 34 42 15 Fax:
+32 16 34 42 05 |
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e-mail: Jan.Deprest@uz.kuleuven.ac.be |
Partners
| Partner 2: |
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Partner 3: |
| Karl Storz Gmbh, Mr Gerard Barki |
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Prof Dr Yves Ville, Université Paris-Ouest |
| Karl Storz Endoskope |
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CHR Poissy-St Germain |
| Mittelstrasse |
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Dept of Gynaecology and Obstetrics |
| 78532 Tuttlingen |
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10 rue du Champ-Gaillard |
| Germany |
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78303 Poissy Cedex, France |
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| Tel: +41 22 735 21 00 |
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Tel: +33 1 39 27 52 51 |
| Fax: +41 22 786 46 00 |
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Fax: +33 1 39 27 44 12 |
| email: barki@swissonline.ch |
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email: yville@wanadoo.fr |
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| Partner 4: |
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Partner 5: |
| Karolinska Hospital – Prof Dr The-Hung Bui |
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Algemeines Krankenhaus Brambek – PD Dr Kurt
Hecher |
| Dept. Molecular Medicine |
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Prenatal Medizin |
| Clinical Genetics Unit Karolinska Hospital |
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Alg Krankenhaus Brambek |
| 171 76 Stockolm |
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benkamp 148 |
| Sweden |
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22291 Hamburg, Germany |
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| Tel: +46 8 517 749 89 |
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Tel: +49 40 63 85 21 00 |
| Fax: +46 8 32 77 34 |
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Fax: +49 40 63 85 21 69 |
| email: The-Hung.Bui@ks.se |
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email: KHecher@compuserve.com |
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| Partner 6: |
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Partner 7: |
| Hôpital Necker – Enfants Malades - Prof Dr
Yves Dumez |
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Universita degli Studi de Milano - Prof Dr Umberto
Nicolini |
| Service Maternité Batiment Sèvres,
Hôpital |
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Instituto Ostetrico Ginecologico |
| Necker-Enfants Malades |
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Universita degli Studi de Milano - Ospedale V Buzzi |
| 149 rue de Sèvres |
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Via Castelvetro 32 |
| 75015 Paris, France |
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20154 Milano, Italy |
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| Tel: +33 1 44 49 40 30 |
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Tel: +39 02 5799 5467 |
| Fax: +33 1 44 49 40 18 |
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Fax: +39 02 5799 5467 |
| email: eurofetus.mahieu@nck.ap-hop-paris.fr |
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email: umberto.nicolini@unimi.it |
| (Partner left research consortium in year
2) |
ABSTRACT:
Background:The unborn fetus has become a patient to whom
diagnosis and therapy is offered prior to birth. These are
preferentially carried out in a non-invasive way. Sometimes a
fetal anomaly or disease may require an invasive procedure to
establish the diagnosis or cure the condition. Under ultrasound
guidance, a needle can be inserted into the amniotic cavity, to
sample the amniotic fluid, fetal blood or administer transfusion
blood or medication. This has acceptable risks and is widely
practiced. In some rare conditions the fetus needs to be operated
on during its intra-uterine life. Fetal surgery then typically
requires maternal laparotomy, hysterotomy, and temporary exposure
of the fetus. Such a procedure is unfortunately associated with
adverse fetal side-effects while being very invasive to the
mother. A minimally invasive endoscopic approach seems therefore
an attractive alternative. In the 1990s the diameter of
endoscopes could be dramatically reduced and videotechnology
boosted endoscopic surgery. However virtually no purpose designed
instruments for use in fetoscopy were available and from an
economical viewpoint, there are not much incentives for the
medical industry to develop these. The field is small and
appreciated as high risk. In addition a strong scientific basis
for the theoretical benefits of operative fetoscopy was lacking,
and the clinical experience present in the late 1990s was limited
and scattered.
Results:The Eurofoetus project is the European answer to
these problems. The consortium achieved to bridge the gap between
early experimental procedures and safe and routine clinical
implementation of operative fetoscopy. Present European expertise
was merged: leading edge medical centres were connected with the
relevant biomedical industry. Clinical partners complementing
each other and a world leading manufacturer of endoscopic
equipment were brought together. More than 10 embryoscopes and
fetoscopes were fabricated and released to production, together
with their accompanying introduction and operative sheaths.
Purpose designed miniature fetoscopic instruments and devices
were designed and tested. Being the only available purpose
designed tools for the fetal medicine specialist, they are and
will continue to be a memory to the EC support for this project
far outside European borders. The consortium has also deployed a
registry to monitor safety of this invasive technique, and
initiated clinical studies that run over the website of the
project. One condition, affecting the monochorionic (having a
single placenta) identical twins, called twin-to-twin transfusion
syndrome, is amenable to fetoscopic therapy. This has become the
most common fetoscopic procedure by now. A clinical study has
been initiated by the consortium, and still continues to evaluate
this procedure. The website of the project further hosts
information to the public, and particularly for patients with
this condition. The group was further able to provide the animal
experimental basis for a technique for sealing the defect in the
fetal membranes, which could prevent the adverse consequences of
rupture of the fetal membranes. It will now need a preclinical
evaluation and clinical study. New instrumentation also allowed
the group to perform the first successful percutaneous fetoscopic
procedure ever treat a baby with congenital diaphragmatic hernia.
Conclusion:The fetus is the patient who benefits the
most of minimally invasive surgery. As it can stay in its natural
environment during the procedure, chances for survival
dramatically improve. Thanks to the support of the EC, fetoscopic
surgery became a clinical reality. A purpose designed line of
microinvasive instruments were developed, and the experimental
basis for their application was laid down. Clinical application
is monitored via a registry and for the most common application
through comparative studies. In addition a technique for treating
the most frequent side effect of invasive procedures like these,
namely rupture of the membranes, is being proposed.
Key Words: fetal therapy - fetal diagnosis - fetal surgery
- endoscopy - fetal medicine - fetoscopy
Deliverables of the project:Publications related to this
project: 50 Peer review and 20 non-peer review literature
publications next to numerous published abstracts.
A whole range of new medical instruments were developed, tested
and subsequently released for production.
- These include endoscopes, accompanying sheats, trocars for
cannula introduction and some purpose designed instruments such
as forceps, scissors, etc… Hardware (i.e. devices
without which endoscopy in the amniotic cavity is not
possible), including devices for distention of the cavity were
purpose designed and tested.
- Two specially designed bipolar forceps and monopolar
coagulation device for cord coagulation in abnormal
monochorionic twins were introduced to the market.
- All the above instruments may also find their place in
other clinical fields (besides fetal medicine), such as
hysteroscopy (for the endoscopes) and pediatric surgery (for
instruments and devices).
- Preclinically the efficacy and safety of a fetal membrane
sealing technique, using collagen, was studied. According to
the contractual agreements, no non-human primate experiments
were allowed, and therefore its application in clinical cases
is still under way. An in vitro culture system for the study of
fetal membrane wound healing was developed which will further
be used by scientists, reducing the need for animal
experiments.
- As part of the workpackage on catheterisation techniques
(aiming at in utero stem cell transplantation), new analytical
techniques to assess small differences in engraftment, and two
methods that may enhance engraftment were developed.
- Via our website, information on fetoscopy is given to the
public. For medical professionals, a registry on fetoscopic
procedures and two clinical studies on the treatment of
twin-to-twin transfusion syndrome are accessible. The website
hosts these clinical studies and all related documents for data
entry. This is the largest dataset worldwide on this condition.
It is expected that by 2003 a randomised trial will be finished
and determine whether TTS is better treated by fetoscopic laser
coagulation than amniodrainage, or perhaps what subgroup would
benefit from either therapy.
The name Eurofoetus achieved a reputation of a scientific
“authority” in the field of fetoscopy and invasive
fetal medicine. Over 400 fetoscopies have been done by the
clinical partners within this contract period. Only one center in
Europe performing operative fetoscopy is not a member of the
Eurofoetus group, but was meanwhile involved in the new project
“EuroTwin2Twin” within the FP5 programme. The
clinicians of the group are considered as world authorities in
fetoscopy: they are opinion leaders and trainers of clinicians
who want to establish a formal fetoscopy programme.
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