Fetoscopic techniques for prenatal covering of gastroschisis in an ovine model are technically demanding and do not lead to permanent anchoring on the fetus until the end of gestation

Surgical Endoscopy volume 35, pages745–753(2021)Cite this article

Abstract

Introduction

This is the cumulative technical report on the operative procedures and limitations of fetoscopic bag insertion, intestinal bag placement, and bag fixation to the fetus in a series of pilot studies in an ovine model for prenatal treatment of gastroschisis.

Material and methods

In 24 German blackhead sheep, a surgically created gastroschisis was managed by fetoscopic placement of the extruded intestines into a bag. The bag was then fastened onto the fetal abdominal wall. Different materials (sterile gloves, latex condoms, laparosopic retrieval bags) and different fixation techniques (laparoscopic staplers, interrupted and continuous sutures) have been examined. The fetuses were retrieved and evaluated at the end of gestation.

Results

Uterine bag insertion was successful in 15 of 24 (62.5%) and intestinal bag placement in 10 of 15 available fetuses (66.6%). The main factor limiting fetoscopic procedures was chorioamniotic separation (CAS). Sterilized condoms provided the most appropriate type of bags and the V-Loc™ running suture, the most expedient type of fixation, which was achieved in 9 of the 10 fetuses (complete = 2, partially = 7) by using a three port access (5 mm and 2 × 3 mm). All bags were encountered completely or partially dislocated from the fetus at the end of gestation.

Conclusions

Fetoscopic intestinal bag placement and fixation in gastroschisis technically demanding. None of the evaluated techniques led to permanent anchorage of the bag to the fetus. The development of specially designed instruments, bags and fixation methods is required to optimize this approach.

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References

  1. 1.

    Bergholz R, Boettcher M, Reinshagen K, Wenke K (2014) Complex gastroschisis is a different entity to simple gastroschisis affecting morbidity and mortality-A systematic review and meta-analysis. J Pediatr Surg 49:1527–1532. https://doi.org/10.1016/j.jpedsurg.2014.08.001

    Article  PubMed  Google Scholar 

  2. 2.

    Marven S, Owen A (2008) Contemporary postnatal surgical management strategies for congenital abdominal wall defects. Semin Pediatr Surg 17:222–235. https://doi.org/10.1053/j.sempedsurg.2008.07.002

    Article  PubMed  Google Scholar 

  3. 3.

    Krebs T, Boettcher M, Schäfer H, Eschenburg G, Wenke K, Appl B, Roth B, Andreas T, Schmitz C, Fahje R, Jacobsen B, Tiemann B, Reinshagen K, Hecher K, Bergholz R (2014) Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis. Surg Endosc. https://doi.org/10.1007/s00464-014-3494-x

    Article  PubMed  Google Scholar 

  4. 4.

    Bergholz R, Krebs T, Wenke K, Andreas T, Tiemann B, Paetzel J, Jacobsen B, Fahje R, Schmitz C, Mann O, Roth B, Appl B, Hecher K (2012) Fetoscopic management of gastroschisis in a lamb model. Surg Endosc 26:1412–1416. https://doi.org/10.1007/s00464-011-2048-8

    Article  PubMed  Google Scholar 

  5. 5.

    Guys JM, Esposito C, Simeoni J, D’Ercole C, Paut O, Bouzid A, Boubli L (2002) An experimental model of gastroschisis using fetoendoscopy: preliminary results and technical considerations. Surg Endosc 16:317–319. https://doi.org/10.1007/s00464-001-9033-6

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Kohl T, Tchatcheva K, Stressig R, Gembruch U, Kahl P (2009) Is there a therapeutic role for fetoscopic surgery in the prenatal treatment of gastroschisis? A feasibility study in sheep. Surg Endosc 23:1499–1505. https://doi.org/10.1007/s00464-009-0394-6

    Article  PubMed  Google Scholar 

  7. 7.

    Kahl P, Buettner R, Tchatcheva K, Stressig R, Gembruch U, Kohl T (2012) Macroscopic and histopathologic findings in a laparoschisis model in fetal sheep: comparisons with gastroschisis in human fetuses and implications for prenatal interventions. Arch Gynecol Obstet 285:15–19. https://doi.org/10.1007/s00404-011-1890-1

    Article  PubMed  Google Scholar 

  8. 8.

    Langer JC, Bell JG, Castillo RO, Crombleholme TM, Longaker MT, Duncan BW, Bradley SM, Finkbeiner WE, Verrier ED, Harrison MR (1990) Etiology of intestinal damage in gastroschisis, II. Timing and reversibility of histological changes, mucosal function, and contractility. J Pediatr Surg 25:1122–1126

    CAS  Article  Google Scholar 

  9. 9.

    Roelofs LAJ, Eggink AJ, Hulsbergen-van de Kaa CA, van den Berg PP, van Kuppevelt TH, van Moerkerk HTB, Crevels AJ, Lotgering FK, Feitz WFJ, Wijnen RMH (2008) Fetal abdominal wall repair with a collagen biomatrix in an experimental sheep model for gastroschisis. Tissue Eng 14:2033–2040. https://doi.org/10.1089/ten.tea.2007.0191

    CAS  Article  Google Scholar 

  10. 10.

    Roelofs LAJ, Geutjes PJ, Hulsbergen-van de Kaa CA, Eggink AJ, van Kuppevelt TH, Daamen WF, Crevels AJ, van den Berg PP, Feitz WFJ, Wijnen RMH (2013) Prenatal coverage of experimental gastroschisis with a collagen scaffold to protect the bowel. J Pediatr Surg 48:516–524. https://doi.org/10.1016/j.jpedsurg.2012.07.056

    Article  PubMed  Google Scholar 

  11. 11.

    Stephenson JT, Pichakron KO, Vu L, Jancelewicz T, Jamshidi R, Grayson JK, Nobuhara KK (2010) In utero repair of gastroschisis in the sheep (Ovis aries) model. J Pediatr Surg 45:65–69. https://doi.org/10.1016/j.jpedsurg.2009.10.012

    Article  PubMed  Google Scholar 

  12. 12.

    Vargun R, Aktug T, Heper A, Bingol-kologlu M (2007) Effects of intrauterine treatment on interstitial cells of Cajal in gastroschisis. J Pediatr Surg 42:783–787. https://doi.org/10.1016/j.jpedsurg.2006.12.062

    Article  PubMed  Google Scholar 

  13. 13.

    Gonçalves FLL, Bueno MP, Schmidt AF, Figueira RL, Sbragia L (2014) Treatment of bowel in experimental gastroschisis with a nitric oxide donor. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2014.09.025

    Article  PubMed  Google Scholar 

  14. 14.

    de Lagausie P, Guibourdenche J, de Buis A, Peuchmaur M, Oury JF, Aigrain Y, Sibony O, Luton D (2002) Esophageal ligature in experimental gastroschisis. J Pediatr Surg 37:1160–1164

    Article  Google Scholar 

  15. 15.

    Till H, Muensterer O, Mueller M, Klis V, Klotz S, Metzger R, Joppich I (2003) Intrauterine repair of gastroschisis in fetal rabbits. Fetal Diagn Ther 18:297–300

    CAS  Article  Google Scholar 

  16. 16.

    Gonçalves FLL, da Silva R, Schmidt AF, de Oliveira MG, Sbragia L (2010) Hydrogel protection: a novel approach to reduce bowel inflammation in experimental gastroschisis. Eur J Obstet Gynecol Reprod Biol 148:35–39. https://doi.org/10.1016/j.ejogrb.2009.10.009

    Article  PubMed  Google Scholar 

  17. 17.

    Guilbaud L, Roux N, Friszer S, Garabedian C, Dhombres F, Bessières B, Fallet-Bianco C, Di Rocco F, Zerah M, Jouannic J-M (2017) Fetoscopic patch coverage of experimental myelomenigocele using a two-port access in fetal sheep. Childs Nerv Syst ChNS 33:1177–1184. https://doi.org/10.1007/s00381-017-3461-7

    Article  PubMed  Google Scholar 

  18. 18.

    Bergholz R, Krebs T, Wenke K, Boettcher M, Andreas T, Tiemann B, Jacobsen B, Fahje R, Schmitz C, Roth B, Appl B, Reinshagen K, Hecher K (2013) Abdominal wall incision with or without exteriorization of bowel: results from a fetal lamb model for the embryogenesis of gastroschisis. Fetal Diagn Ther 33:55–60. https://doi.org/10.1159/000342421

    Article  PubMed  Google Scholar 

  19. 19.

    Hughes M, Health JBS of P the principles of humane experimental technique. In: Johns Hopkins Bloom. Sch. Public Health. https://altweb.jhsph.edu/pubs/books/humane_exp/het-toc. Accessed 12 Feb 2019

  20. 20.

    Mietzsch S, Boettcher J, Yang S, Chantereau P, Romero P, Bergholz R, Reinshagen K, Boettcher M (2016) Training significantly improves fetoscopy performance: a pilot randomized controlled trial. Eur J Pediatr Surg 26:436–442. https://doi.org/10.1055/s-0035-1564712

    Article  PubMed  Google Scholar 

  21. 21.

    Baschat AA, Ahn ES, Murphy J, Miller JL (2018) Fetal blood-gas values during fetoscopic myelomeningocele repair performed under carbon dioxide insufflation. Ultrasound Obstet Gynecol 52:400–402. https://doi.org/10.1002/uog.19083

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Kohl T (2016) Impact of partial amniotic carbon dioxide insufflation (PACI) on middle cerebral artery blood flow in mid-gestation human fetuses undergoing fetoscopic surgery for spina bifida aperta. Ultrasound Obstet Gynecol 47:521–522. https://doi.org/10.1002/uog.15761

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Mann LK, Papanna R, Moise KJ, Byrd RH, Popek EJ, Kaur S, Tseng SCG, Stewart RJ (2012) Fetal membrane patch and biomimetic adhesive coacervates as a sealant for fetoscopic defects. Acta Biomater 8:2160–2165. https://doi.org/10.1016/j.actbio.2012.02.014

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Haller CM, Buerzle W, Brubaker CE, Messersmith PB, Mazza E, Ochsenbein-Koelble N, Zimmermann R, Ehrbar M (2011) Mussel-mimetic tissue adhesive for fetal membrane repair: a standardized ex vivo evaluation using elastomeric membranes. Prenat Diagn 31:654–660. https://doi.org/10.1002/pd.2712

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Kivelio A, Dekoninck P, Perrini M, Brubaker CE, Messersmith PB, Mazza E, Deprest J, Zimmermann R, Ehrbar M, Ochsenbein-Koelble N (2013) Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits. Eur J Obstet Gynecol Reprod Biol. https://doi.org/10.1016/j.ejogrb.2013.09.003

    Article  PubMed  Google Scholar 

  26. 26.

    Fontecha CG, Peiro JL, Sevilla JJ, Aguirre M, Soldado F, Fresno L, Fonseca C, Chacaltana A, Martinez V (2011) Fetoscopic coverage of experimental myelomeningocele in sheep using a patch with surgical sealant. Eur J Obstet Gynecol Reprod Biol 156:171–176. https://doi.org/10.1016/j.ejogrb.2010.12.046

    Article  PubMed  Google Scholar 

  27. 27.

    Fontecha CG, Peiro JL, Aguirre M, Soldado F, Añor S, Fresno L, Martinez-Ibañez V (2009) Inert patch with bioadhesive for gentle foetal surgery of myelomeningocele in a sheep model. Eur J Obstet Gynecol Reprod Biol 146:174–179. https://doi.org/10.1016/j.ejogrb.2009.06.022

    Article  PubMed  Google Scholar 

  28. 28.

    Belfort MA, Whitehead WE, Shamshirsaz AA, Bateni ZH, Olutoye OO, Olutoye OA, Mann DG, Espinoza J, Williams E, Lee TC, Keswani SG, Ayres N, Cassady CI, Mehollin-Ray AR, Sanz Cortes M, Carreras E, Peiro JL, Ruano R, Cass DL (2017) Fetoscopic open neural tube defect repair: development and refinement of a two-port, carbon dioxide insufflation technique. Obstet Gynecol 129:734–743. https://doi.org/10.1097/AOG.0000000000001941

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Belfort M, Deprest J, Hecher K (2016) Current controversies in prenatal diagnosis 1: in utero therapy for spina bifida is ready for endoscopic repair. Prenat Diagn 36:1161–1166. https://doi.org/10.1002/pd.4972

    Article  PubMed  Google Scholar 

  30. 30.

    Belfort MA, Whitehead WE, Bednov A, Shamshirsaz AA (2017) Low-fidelity simulator for the standardized training of fetoscopic meningomyelocele repair. Obstet Gynecol. https://doi.org/10.1097/AOG.0000000000002406

    Article  PubMed  Google Scholar 

  31. 31.

    Midrio P, Faussone-Pellegrini MS, Vannucchi MG, Flake AW (2004) Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells. J Pediatr Surg 39:1541–1547. https://doi.org/10.1016/j.jpedsurg.2004.06.017

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Midrio P, Vannucchi MG, Pieri L, Alaggio R, Faussone-Pellegrini MS (2008) Delayed development of interstitial cells of Cajal in the ileum of a human case of gastroschisis. J Cell Mol Med 12:471–478. https://doi.org/10.1111/j.1582-4934.2008.00277.x

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Auber F, Danzer E, Noché-Monnery M-E, Sarnacki S, Trugnan G, Boudjemaa S, Audry G (2013) Enteric nervous system impairment in gastroschisis. Eur J Pediatr Surg 23:29–38. https://doi.org/10.1055/s-0032-1326955

    Article  PubMed  Google Scholar 

  34. 34.

    Nagy B (2019) Cell-free nucleic acids in prenatal diagnosis and pregnancy-associated diseases. EJIFCC 30:215–223

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Hijkoop A, Lap CCMM, Aliasi M, Mulder EJH, Kramer WLM, Brouwers HAA, van Baren R, Pajkrt E, van Kaam AH, Bilardo CM, Pistorius LR, Visser GHA, Wijnen RMH, Tibboel D, Manten GTR, Cohen-Overbeek TE (2019) Using three-dimensional ultrasound in predicting complex gastroschisis: a longitudinal, prospective, multicenter cohort study. Prenat Diagn 39:1204–1212. https://doi.org/10.1002/pd.5568

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Dewberry LC, Hilton SA, Zaretsky MV, Behrendt N, Galan HL, Marwan AI, Liechty KW (2019) Examination of prenatal sonographic findings: intra-abdominal bowel dilation predicts poor gastroschisis outcomes. Fetal Diagn Ther. https://doi.org/10.1159/000501592

    Article  PubMed  Google Scholar 

  37. 37.

    Oakes MC, Porto M, Chung JH (2018) Advances in prenatal and perinatal diagnosis and management of gastroschisis. Semin Pediatr Surg 27:289–299. https://doi.org/10.1053/j.sempedsurg.2018.08.006

    Article  PubMed  Google Scholar 

  38. 38.

    Robertson JA, Kimble RM, Stockton K, Sekar R (2017) Antenatal ultrasound features in fetuses with gastroschisis and its prediction in neonatal outcome. Aust N Z J Obstet Gynaecol 57:52–56. https://doi.org/10.1111/ajo.12565

    Article  PubMed  Google Scholar 

  39. 39.

    Andrade WS, Brizot ML, Rodrigues AS, Tannuri AC, Krebs VL, Nishie EN, Francisco RPV, Zugaib M (2018) Sonographic markers in the prediction of fetal complex gastroschisis. Fetal Diagn Ther 43:45–52. https://doi.org/10.1159/000464245

    Article  PubMed  Google Scholar 

  40. 40.

    Andrade WS, Brizot ML, Francisco RPV, Tannuri AC, Syngelaki A, Akolekar R, Nicolaides KH (2019) Fetal intra-abdominal bowel dilation in prediction of complex gastroschisis. Ultrasound Obstet Gynecol 54:376–380. https://doi.org/10.1002/uog.20367

    CAS  Article  PubMed  Google Scholar 

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Acknowledgements

Robert Bergholz and Thomas Krebs contributed equally to this manuscript

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Author notes

  1. Robert Bergholz and Thomas Krebs contributed equally to this manuscript.

Affiliations

  1. Department of General-, Visceral-, Thoracic-, Transplant- and Pediatric Surgery, University Hospital of Schleswig-Holstein, UKSH Kiel Campus, Arnold-Heller-Strasse 3, 20415, Kiel, Germany

    Robert Bergholz

  2. Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Robert Bergholz, Birte Cremieux, Carla Georgi, Felipe Fromm, Michael Boettcher, Katharina Wenke & Konrad Reinshagen

  3. Department of Pediatric Surgery, Ostschweizer Children’s Hospital, Claudiusstrasse 6, 9006, St. Gallen, Switzerland

    Thomas Krebs & Thomas Andreas

  4. Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Kurt Hecher

  5. Department of Experimental Animal Research, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Bastian Tiemann

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  1. Robert Bergholz
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Disclosures

Robert Bergholz and Thomas Krebs were promoted by a grant of the foundation “Hamburg macht Kinder gesund e.V. Robert Bergholz and Thomas Krebs received funding by Karl Storz Company GmbH, Tuttlingen, Germany, in form of materials (Storz Camera Telepack, Storz 3- and 5-mm laparoscopic instruments). Birte Cremieux, Carla Georgi, Felipe Fromm, Michael Boettcher, Thomas Andreas, Bastian Tiemann, Katharina Wenke, Konrad Reinshagen and Kurt Hecher have no conflict of interest of financial ties to disclose.

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Bergholz, R., Krebs, T., Cremieux, B. et al. Fetoscopic techniques for prenatal covering of gastroschisis in an ovine model are technically demanding and do not lead to permanent anchoring on the fetus until the end of gestation. Surg Endosc 35, 745–753 (2021). https://doi.org/10.1007/s00464-020-07441-7

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Keywords

  • Animal model
  • Fetal surgery
  • Fetendo
  • Fetoscopy
  • Fetus
  • Gastroschisis
  • Prenatal treatment