PMID- 25515126 OWN - NLM STAT- MEDLINE DCOM- 20151130 LR - 20181113 IS - 1433-0458 (Electronic) IS - 0017-6192 (Linking) VI - 63 IP - 3 DP - 2015 Mar TI - [Importance of cellular tight junction complexes in the development of periprosthetic leakage after prosthetic voice rehabilitation]. PG - 171-2, 174-8, 180-1 LID - 10.1007/s00106-014-2951-0 [doi] AB - BACKGROUND: The use of voice prostheses is currently the gold standard in voice rehabilitation after total laryngectomy. This method combines low complication rates and excellent rehabilitation results; however, approximately 30% of patients show periprosthetic leakage or severe fistula enlargement after laryngectomy and prosthetic voice restoration within the first 4 years. The development of this enlargement is controversially discussed in the literature but recently published studies have shown that high esophageal reflux plays a key role in this process, which leads to an inflammatory reaction and disturbs the intercellular tight junctions in the sense of an epithelial mesenchymal transition (EMT). MATERIAL AND METHODS: A total of 44 patients underwent 24 h pH monitoring, a sample biopsy from the region of the fistula and a subsequent biomolecular examination for intracellular junction proteins as well as a correlation between the severity of reflux and tracheoesophageal fistula problems before and after antireflux therapy with proton pump inhibitors (PPI). RESULTS: Immunohistochemical staining revealed decreases in membrane E-cadherin and beta-catenin and a significant increase in the cytoplasmic fraction, depending on the severity of inflammation in the fistula tissue. In patients with an improvement of clinical fistula problems under oral PPI treatment an increase of membrane E-cadherin could be shown, whereas patients with persisting fistula enlargement demonstrated a further decrease of E-cadherin. CONCLUSION: The data indicate a central role of EMT in the development of fistula enlargement after total laryngectomy. Patients with periprosthetic leakage showed a loss of membrane bound E-cadherin and beta-catenin with an up-regulation of vimentin expression. In patients with mild or no leakage problems EMT could be resolved by aggressive antireflux treatment, whereas patients without any effect of PPI treatment on the fistula showed no reversal of EMT. These data contribute to the understanding of treatment resistant fistula enlargement after total laryngectomy. FAU - Lorenz, K J AU - Lorenz KJ AD - Klinik fur Hals-Nasen-Ohrenheilkunde, Kopf-Hals-Chirurgie, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Deutschland, kai.lorenz@extern.uni-ulm.de. FAU - Kraft, K AU - Kraft K FAU - Graf, F AU - Graf F FAU - Propper, C AU - Propper C FAU - Steinestel, K AU - Steinestel K LA - ger PT - Clinical Trial PT - English Abstract PT - Journal Article TT - Bedeutung zellularer Tight-junction-Komplexe bei der Entwicklung einer periprothetischen Leckage bei stimmprothetischer Versorgung. PL - Germany TA - HNO JT - HNO JID - 2985099R RN - 0 (Tight Junction Proteins) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Gastroesophageal Reflux/*etiology/metabolism/*pathology MH - Humans MH - Laryngectomy/*adverse effects/*rehabilitation MH - Larynx, Artificial/*adverse effects MH - Male MH - Middle Aged MH - Tight Junction Proteins/metabolism MH - Tight Junctions/*metabolism/pathology MH - Treatment Outcome EDAT- 2014/12/18 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/12/18 06:00 PHST- 2014/12/18 06:00 [entrez] PHST- 2014/12/18 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - 10.1007/s00106-014-2951-0 [doi] PST - ppublish SO - HNO. 2015 Mar;63(3):171-2, 174-8, 180-1. doi: 10.1007/s00106-014-2951-0.