200 FUTURE RESEARCH INTRODUCTION This thesis revealed a yet unexplained recurrence after 2-duct ligation (2-DL), for which additional treatment is indicated in one-third of patients. Alternative salivary pathways were proposed as the leading reason for recurrence and treatment failure of 2-DL; nuclear imaging revealed uptake and washout of radionucleotides of the submandibular salivary glands after 2-DL with ligatures.52, 57 Upon re-exploration in 2 patients, alternative duct openings were present distal to the sublingual caruncle. It is thought that the use of ligatures rather than clips increases this risk by potential ligature slipping, increased tissue reaction and eventually fistulation. This finding that 3 out of 4 patients, in whom ligatures were used, required additional treatment after 2-DL substantiates this theory. These numbers are too small to draw definitive conclusions, and it should be noted that recurrence was also observed after 2-DL with vascular clips instead of ligatures.68 A potential route for alternative salivary pathways is backflow through the duct of Bartholin. When the submandibular duct is clipped distally to the duct of Bartholin, one could expect submandibular saliva to find its way into the duct of Bartholin and eventually drain into the floor-of-mouth via the ducts of Rivinus.31, 52 In summary, 2-DL seems to be advantageous over surgical procedures as SMDR and SMGE,53 because it is a significantly shorter surgical procedure including a less extensive dissection, and there is a slightly lower risk for adverse events. Moreover, 2-DL seems to rival BoNT-A because there is only a slightly greater risk for adverse events, but the drooling reduction is significantly greater and, obviously, longerlasting. There is, nevertheless, a certain relapse after 2-DL, which is predominantly attributed to alternative salivary pathways.59, 68 The findings in the studies mentioned above led to the initiative to evaluate a modification of 2-DL to prevent alternative salivary pathway formation.
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