Denise Araujo Lapa Pedreira

Fetoscopic single-layer repair of open spina bifida using a cellulose patch: preliminary clinical experience.

Abstract Objective: To report our preliminary clinical experience in the antenatal correction of open spina bifida (OSB) using a fetoscopic approach and a simplified closure technique. Methods: Four fetuses with lumbar-sacral defects were operated in utero from 25 to 27 weeks. Surgeries were performed percutaneously under general anesthesia using three trocars and partial carbon dioxide insufflation. After dissection of the neural placode, the surrounding skin was closed over a cellulose patch using a single continuous stitch. Results: Surgical closure was successful in three of the four cases. All successful cases showed improvement of the hindbrain herniation and no neonatal neurosurgical repair was required in two cases. Delivery occurred between 31 and 33 weeks, and no fetal or neonatal deaths occurred. Ventriculoperitoneal shunting was not needed in two out of the 3 successful cases. Conclusions: Our preliminary experience suggests that definitive fetoscopic repair of OSB is feasible using our innovative surgical technique. A phase I trial for the fetoscopic correction of OSB with this technique is currently being conducted.

Successful Fetal Surgery for the Repair of a ‘Myelomeningocele-Like’ Defect Created in the Fetal Rabbit

Objective: To study the correction of a ‘myelomeningocele-like’ defect in fetal rabbits. Methods: Twelve pregnant rabbits had a spinal defect surgically created in 40 of their fetuses at 23 days of gestation. Immediate repair was performed in 30 fetuses (group I), and 10 remained uncorrected (group II). After 30 days, the fetuses were harvested and the anatomopathological aspects where compared using Fisher’s exact test. Results: Three different techniques to apply a cellulose graft were used for correction in 8 (technique A), 7 (technique B), and 15 animals (technique C), but only one (technique C) was successful. The survival rate at 30 days was 66.7% (10/15) in group I and 80% (8/10) in group II. A ‘myelomeningocele-like’ defect was present in all fetuses in group II, while in group I the defect was successfully repaired in 80% of the surviving fetuses (p < 0.01). Conclusion: The surgically created spinal defect was successfully repaired, and also the fetal rabbit could be established as a model for the study of intrauterine correction of a myelomeningocele-like defect.

Gasless Fetoscopy: A New Approach to Endoscopic Closure of a Lumbar Skin Defect in Fetal Sheep

Objective: To develop a new endoscopic approach to the correction of a myelomeningocele-like defect in fetal sheep. Methods: The fetuses of 9 pregnant ewes, with an average gestational age of 115 days, were subjected to a 3.0 × 2.0 cm removal of the skin over the lumbar spine, performed through hysterotomy. The uterus was closed, and three 5-mm endoscopic cannulas, without valve mechanisms, were inserted. In the pilot phase (2 animals), we initially worked exclusively in the amniotic fluid space. In the study phase, we partially withdrew the fetus from the amniotic fluid to completely expose its back. By simply allowing air to enter the amniotic cavity (without gas injection), a working space was created using a uterine lift device. The skin around the defect was dissected, and a biosynthetic cellulose material was applied to cover the area. A continuous suture of the skin was performed to completely hide the material. Results: The combined air/fluid space allowed the skin to be successfully closed in 6 out of 7 cases in the study phase. All fetuses were alive at the end of the procedures. Time to complete the endoscopic part of the procedure fell from 3 to 1 h by the end of this series. Premature birth occurred in 2 of the 4 cases allowed to continue with the pregnancy. Conclusion: A new gasless fetoscopic surgery technique was developed as an alternative to current techniques used for fetal endoscopic surgery.

A Different Technique to Create a ‘Myelomeningocele-Like’ Defect in the Fetal Rabbit

Objective: To evaluate the fetal survival rate using a modified technique to surgically create a ‘myelomeningocele-like’ defect in a rabbit model. Methods: Six white New Zealand rabbits had a spinal defect created in their fetuses at 23 days of gestation. At 30 days of gestation, the fetuses were harvested for anatomo-pathologic evaluation. Results: The defect was created in 19 fetuses and an attempt to correct it was made in 15 cases (group I), and 4 fetuses where left without correction (group II). At 30 days, a ‘myelomeningocele-like’ defect was present in all surviving fetuses. The total survival rate was 73.68% (14/19); 11 fetus survived in group I and 3 in group II. Conclusion: The technical modifications, including fetal positioning and exposure of its back prior to the incision of the lamina, associated with a different technique for myometrium closure, offer an alternative and probably safer method to surgically create a spinal defect in the fetal rabbit.

Simplified correction of a meningomyelocele-like defect in the ovine fetus

PURPOSE To develop a simplified technique for antenatal correction of a meningomyelocele -like defect in fetal sheep to allow direct skin closure. METHODS A spinal defect was surgically created at 75 days of gestation in the fetuses of 36 pregnant sheep, 23 survived the surgery. At 102 days gestation, the defect was corrected in 14 cases (9 were left untreated). Skin surrounding the defect was dissected below the dermis to permit its edges to be approximated and sutured, without interposing any material to its edges. An interface material intended to protect the neural tissue from skin adhesion was used and the skin defect was completely closed over it. Pregnancy was allowed to continue up to 138 days gestation, the fetuses were submitted to macroscopic and microscopic analysis. RESULTS The defect was successfully corrected in 90.9% in the experimental group, and spontaneous closure occurred in 22.3% in the control group (p < 0.05). The survival rate after the creation and correction of the defect was 63.4% and 78% respectively. CONCLUSION This simplified technique was successful in the correction a meningomyelocele-like defect, in the fetal sheep.

Neoskin development in the fetus with the use of a three-layer graft: an animal model for in utero closure of large skin defects

Objective: To assess the ability of a three-layer graft in the closuse of large fetal skin defects. Methods: Ovine fetuses underwent a large (4 × 3 cm) full-thickness skin defect over the lumbar region at 105 days’ gestation (term = 140 days). A bilaminar artificial skin was placed over a cellulose interface to cover the defect (3-layer graft). The skin was partially reapproximated with a continuous nylon suture. Pregnancy was allowed to continue and the surgical site was submitted to histopathological analysis at different post-operative intervals. Results: Seven fetuses underwent surgery. One maternal/fetal death occurred, and the remaining 6 fetuses were analyzed. Artificial skin adherence to the wound edges was observed in cases that remained in utero for at least 15 days. Neoskin was present beneath the silicone layer of the bilaminar artificial skin. Conclusions: Our study shows that neoskin can develop in the fetus using a 3-layer graft, including epidermal growth beneath the silicone layer of the bilaminar skin graft. These findings suggest that the fetus is able to reepithelialise even large skin defects. Further experience is necessary to assess the quality of this repair.

Comparison between two surgical techniques for prenatal correction of meningomyelocele in sheep

OBJETIVO: Comparar a tecnica neurocirurgica classica a uma nova tecnica simplificada, para correcao de mielomeningocele, em fetos de ovelhas. METODOS: Em 9 fetos, foi criado um defeito semelhante a mielomeningocele (laminectomia e excisao de dura-mater) no 90o dia de gestacao. O tipo de correcao foi randomizado. No Grupo 1, o defeito foi corrigido usando a tecnica neurocirurgica classica, com a sutura de tres camadas (dura-mater, musculo e pele), realizada por um neurocirurgiao. No Grupo 2, um especialista em Medicina Fetal utilizou a tecnica simplificada, colocando um fragmento de celulose biossintetica sobre a medula e suturando apenas da pele sobre a celulose. Proximo ao termo da gestacao (132 dias), os fetos foram sacrificados para analise anatomopatologica. RESULTADOS: Ocorreram dois casos de aborto e uma morte materna, restando seis casos para avaliacao - tres em cada grupo. No Grupo 1, todos os casos mostraram aderencia da medula a cicatriz (meningoadesao) e perda da arquitetura medular, com destruicao do funiculo posterior e perda da visualizacao da substância cinzenta. No Grupo 2, observou-se, em todos os casos, a formacao de uma neodura-mater, separando o tecido nervoso do musculo adjacente, sendo que o funiculo posterior e a substância cinzenta estavam preservados. CONCLUSAO: A tecnica simplificada foi superior a neurocirurgica, com maior preservacao da medula e evitando as aderencias do tecido nervoso. Os presentes achados sugerem que a tecnica utilizada atualmente na correcao de mielomeningocele em fetos humanos deva ser reavaliada.

Keeping it simple: a “two-step” approach for the fetoscopic correction of spina bifida

I have read with great interest the article by Kohl et al. [1]. We believe the article has many valuable lessons, and we would like to comment on the surgical technique used by the authors to close spina bifida defects [1, 2]. Our objective is to introduce the concept of a two-step approach for fetoscopic correction of this abnormality. Since 2002, our group has been working to develop a simplified correction technique [3–7], to be applied using fetoscopy. The simplified technique we have developed involves a simple dissection of the skin surrounding the lesion, placement of a piece of biosynthetic cellulose (produced by bacteria) over the untouched placode, and placement of a continuous running suture to close the skin. This way the cellulose is kept in place (over the placode) without the need for stitches [3]. Using this technique, we additionally found that the cellulose induced the formation of a new fibroblast layer over the medulla that was in anatomical continuity with the original dura mater (neodura mater) [6]. The new dura mater formed may have an additional effect of protecting the medulla, preventing its adherence to the skin scar and possibly providing a watertight dural closure (Figs. 1, 2). In a previous report in this journal, Kohl et al. [2] described the use of three layers of interrupted sutures to close the defect using fetoscopy in two human fetuses. An absorbable patch was fixed to the paraspinal muscle, then the skin was approximated to the edges of this patch, and finally a nonabsorbable patch was superimposed over the previous patch. We argue against the need to use nonabsorbable material to cover the absorbable material if the fetal skin can be dissected and closed over the lesion. In the study by Kohl et al. [1], chorioamniotic membrane separation was a frequent complication of their fetoscopic procedure, occurring in 7 of 16 cases of spina bifida correction. The authors hypothesized that the separation was probably caused by the multiple trocar manipulations required throughout the procedure. This suggests that the use of our simplified closure technique [7] could reduce the occurrence of chorioamniotic membrane separation. We have recently developed a new endoscopic approach to fetal meningomyelocele repair that we named ‘‘gasless fetoscopy’’ [7]. We have used this technique on sheep fetuses using a combination air-and-fluid medium very similar to the combined gas/fluid medium used by Kohl et al. [1]. We agree with Kohl et al. [1] that this combined intrauterine air/liquid medium is a ‘‘key element’’ in the success of the endoscopic correction of spina bifida. Comparing the series of Kohl et al. [1] with ours [7], there is a significant difference in the average time to perform the endoscopic surgery, 286 vs. 130 min, respectively. This difference can most likely be attributed to the correction technique itself and favors the use of our simplified technique. The initial concept supporting the prenatal correction of spina bifida was to provide the medulla with protection from harmful exposure to the amniotic fluid and to reduce the potential for mechanical damage [8]. From a historical point of view, the first human fetuses were operated using fetoscopy [9], but the poor initial results led to a shift to an open fetal surgery approach. The open surgery approach allowed the defect to be corrected using the same neurosurgical technique as that applied to a newborn. To perform a ‘‘definitive’’ correction of the defect just seemed logical, D. A. L. Pedreira (&) Pathology Department, Faculty of Medicine, University of São Paulo (USP), São Paulo, Brazil e-mail: wdpedreira@uol.com.br

Fetoscopy for meningomyelocele repair: past, present and future.

ABSTRACT Meningomyelocele is a malformation with high prevalence, and one of its main comorbidities is Arnold-Chiari malformation type II. The intrauterine repair of this defect has been studied to reduce the progressive spinal cord damage during gestation. The purpose of the present review was to describe the evolution of fetal surgery for meningomyelocele repair. Searches on PubMed database were conducted including articles published in the last 10 years. Twenty-seven articles were selected, 16 experimental studies and 11 studies in humans. A recent study demonstrated that the fetal correction results in better prognosis of neurological and psychomotor development, but open surgery, which has being used widely, has considerable maternal risks. Studies in animal and human models show that the endoscopic approach is feasible and leads to lower maternal morbidity rates. Two endoscopic techniques are currently under assessment - one in Germany and another in Brazil, and we believe that the endoscopic approach will be the future technique for prenatal repair of this defect.

Estudo de uma nova técnica para criação cirúrgica de um defeito semelhante a meningomielocele em fetos de coelhos

OBJETIVO: Avaliar a sobrevida fetal usando uma nova tecnica cirurgica para criacao de um defeito semelhante a meningomielocele em fetos de coelho. METODOS: Foram utilizadas seis coelhas da linhagem Nova Zelândia que tiveram um defeito espinhal criado em seus fetos no 23° dia de gestacao. O defeito foi criado em 19 fetos e a tentativa de correcao foi feita em 15 casos (grupo I), 4 fetos permaneceram sem correcao (grupo II). No 30° dia de gestacao, os fetos foram submetidos a avaliacao anatomo-patologica. RESULTADOS: No 30° dia a meningomielocele estava presente em todos os fetos sobreviventes. A sobrevida total foi de 73,68% (14/19), 11 fetos sobreviveram no grupo I, e 3 no grupo II. CONCLUSAO: A tecnica modificada apresenta sobrevida fetal satisfatoria, no modelo experimental de criacao de defeito espinhal em fetos.