Sialendoscopy University of UCSF Update Stenoses RAI Sjogrens Search: Iowa Protocols Access “Iowa H+N Protocols” Google/Bing: “Iowa Protocols” or Type “topic term” and “Iowa” Type search term Disclosures: - Consultant to COOK Medical The University of Iowa Research Foundation (UIRF)and Dr. Hoffman filed - a provisional patent application April 11 2013 “Transilluminating Obturator” UIK-04301 - a patent March 25 2009 (US Patent) and March 19 2010 (International Patent: PCT/US2010/027995) Portions of possible future profits from devices associated with these patents will be disbursed through the UIRF with Henry Hoffman listed as one of the recipients

Sodium iodide symporter (NIS) transports iodide by same mechanism into thyroid and salivary tissue -- major and minor salivary glands Immunohistochemical parotid stain for NIS ‘provided by Gainor D*, Chute D# and Lorenz R*, Cleveland Clinic’ *= Dept of Otolaryngology,    # = Dept of Anatomic Pathology, staining absent in acinar tissue intense staining of striated ducts

Radioiodine Sialadenitis key points: Prevention best by avoiding treatment with I131 when possible (contemporary use less common) 2. “Cincinnati regimen” reports best results, not duplicated in other reports 3. Amifostine fallen out of favor 4. Ductal injury logically supports: a. Early intervention ? Steroid infusion ? Hydroexpansion ? Mechanical expansion w or w/o sialendoscopy b. Considerations for research study ? Prophylactic ductal infusion (botox/steroid/other) 5. Treatment after injury detected (xerostomia / salivary swelling and pain) may be too late

“Cincinnati regimen” intense sialorrheic management with hydration during and after I131 treatment Silberstein 2008 [vi] oral 8 mg of dexamethasone and 100 mg of dolasetron 2 hours before therapy and every 12 hours for 5 doses after I131 ingestion 2,400 mL of nondairy liquid per day for the week after therapy Sugar-free gum or candy in the mouth at all times when awake for a week and for the first 3 nights, awaken every three hours to reapply sialogogues and then brush mouth with soft toothbrush and water for one minute Remarkably low incidence of salivary problems supports further investigation of this approach. Unclear as to contribution provided by dexamathasone (anti-inflammatory) and dolasetron (secretogogue) which were given primarily for their anti-emetic properties Silberstein EG: Reducing the Incidence of I131 –Induced Sialadenitis: the role of Pilocarpine TheJournal of Nuclear Medicine vol 49 No 4 April 2008 pp 546-549

Radioiodine Sialadenitis key points: Prevention best by avoiding treatment with I131 when possible (contemporary use less common) 2. “Cincinnati regimen” reports best results, not duplicated in other reports 3. Amifostine fallen out of favor 4. Ductal injury logically supports: a. Early intervention ? Steroid infusion ? Hydroexpansion ? Mechanical expansion w or w/o sialendoscopy b. Considerations for research study ? Prophylactic ductal infusion (botox/steroid/other) 5. Treatment after injury detected (xerostomia / salivary swelling and pain) may be too late

AECG (American-European Consensus Group) Primary Sjogren's: requires 4 of the 6 criteria below, including either positive antibodies or positive lip biopsy Secondary Sjogren's requires diagnosis of connective tissue disease and one sicca symptom and 2 out of the 3 objective tests for either xeropthalmia (ocular) or xerostomia (oral) symptoms 1.+'v anti-SSA and/or SSB 2.Lip Biopsy 3.Oral Symptoms(1of3) Dry mouth > 3 months 4.Oral Test(1of3) Unstim saliv flow <.1mL/min 5.Ocular Symptoms(1of3) Dry eyes > 3 months 6.Ocular Tests(1of2) positive focus score >0.25 mm2 Swollen salivary glands Abnormal parotid Sialography Foreign body sensation in eye +'ve slit lamp exam see Lip biopsy Need liquids to swallow Abnormal salivary scintigraphy Use of artificial tears >3 x per day )+'ve Schirmer's test AECG (American-European Consensus Group) 2002

 Lip Biopsy -  useful for selected cases but 'noted inconsistency and unreliability with the lip biopsy' (ref Bamba et al) False negative biopsy: common when on immunosuppressive medication (including corticosteroids) False negative in the face of chronic Sjogren's syndrome with atrophy and fibrosis of salivary glands (long standing Sjogren's may not benefit) Cigarette smoking (Manthorpe 2000) Sialography felt to be diagnostically more sensitive but less specific than labial salivary gland biopsy (Daniels et al 1996) False positive Aging, trauma, hepatitis C, lymphoma, graft v host disease, sarcoidosis (Huo et al 2010) Not useful in the face of elevated anti-SSA or anti-SSB antibodies (reliably predict positive results of a lip biopsy) 4. Useful in selected cases of suspected Sjogren's in the face of negative ANA, RF, anti-SSA or anti-SSB antibodies. 5. Suggested by Huo et al that 'lip biopsy be reserved only for patients whose serological tests for ANA, RF, anti-SS-A and anti-SS-B are all negative" (Huo et al 2010) 6. Technique: Lip biopsy for minor salivary gland (biopsy for Sjogren's syndrome)

Sjogrens Syndrome key points: Optimal approach to establishing diagnosis is controversial A. Recognize other causes for xerostomia / salivary swelling (e.g.: diabetic (sialosis = salivary swelling) on antidepressants (xerostomia) B. ? Lip bx vs Sialogram Management warrants Rheumatology involvement In-office vs in-O.R. salivary duct cannulation/dilation/steroid insufflation A Likely to benefit swelling and pain B Less likely to benefit xerostomia 4. Future developments: ? Infusion of restasis (cyclosporin)

43 yo with R parotid painful swelling with meals beginning 5 years prior to referral to our clinic 12-01-2011 Minor discomfort ‘all the time’ Major swelling requiring antibiotics every 3 to 4 months No rheumatoid problems no dry eyes or dry mouth Previous tx elsewhere: effort to dilate the duct opening; tympanic neurectomy on R with no benefit

Right parotid sialogram done 12 19 2011 High-grade stricture of the main parotid duct 6 cm from the duct orifice causing diffuse sialectasis of the right intraglandular parotid ducts

Our surgical intervention 12/28/2011 by way of a right-sided parotid sialoendoscopy identified the narrowing with current limitations in technology manifest by our efforts to use multiple different devices to enlarge the area of narrowing by way of dilation, including use of a basket and a Fogarty catheter

April 2012

4 months after parotidectomy 4 months after parotiectomy 4 months after parotidectomy With no symptoms

Ductal Stenoses key points: In my hands sialography is an important diagnostic study Imaging of the ductal system difficult with other methods, including MR sialography Some strictures are easy (thin membrane; distal) many are difficult Current methods of dilation require improvement The strictures in most need of dilation are too small to get a dilator in Need for adjuvants to maintain patency – stents still questions remain about benefit, type, duration