Jia-Zeng Su

Microvascular autologous transplantation of partial submandibular gland for severe keratoconjunctivitis sicca

Objective To evaluate the feasibility of microvascular autologous transplantation of partial submandibular gland (SMG) to prevent or reduce epiphora in severe keratoconjunctivitis sicca (KCS). Methods A total of 39 patients with KCS, covering 42 eyes, were randomised to undergo transplantation of partial or total SMG from January 2006 to December 2009. Clinical data of survival rate of transplanted SMG, ophthalmologic features of best-corrected visual acuity, Schirmer test results, break-up time (BUT) of tear film, fluorescence staining, incidence of postoperative epiphora and frequency of subsequent surgery were compared between two groups. Results Total SMG transplantation was performed in 22 eyes, and partial SMG transplantation was performed in the other 20 eyes. All transplanted SMGs survived. Microvascular crisis occurred in one case of partial SMG transplantation, but the gland survived after exploration to remove the venous thrombus. Obstruction of the ductal orifice in one case of partial SMG transplantation was resolved by reconstruction of the ductal orifice. Symptoms of dry eyes disappeared, and patients were able to discontinue use of artificial tears. Severe epiphora occurred in 6 eyes undergoing partial SMG transplantation and in 19 eyes undergoing total SMG transplantation (p<0.01). Surgical reduction was performed in 6 eyes undergoing partial SMG transplantation and 18 eyes undergoing total SMG transplantation (p<0.01). Conclusions Microvascular transplantation of partial SMG is feasible and effective for severe KCS and does not decrease the survival rate of transplanted SMG. For ample SMGs with normal function, transplantation of partial SMG alleviates the symptoms of dry eye and significantly reduces the incidence of severe postoperative epiphora.

Microvascular autologous submandibular gland transplantation in severe cases of keratoconjunctivitis sicca

Dry eye syndrome is a relatively common disease of the tears and ocular surfaces that results in discomfort, visual disturbance, and tear film instability with possible damage to the ocular surfaces. Microvascular submandibular gland (SMG) transfer offers a surgical alternative for a permanent autologous substitution of tears using the basal secretion of a transplanted SMG. Long-term follow-up reveals that this technique is a lasting and effective solution for patients with severe dry eye syndrome. The uncomfortable symptoms were relieved, and the frequency of use of pharmaceutical tear substitutes was reduced. Objective examination showed significant improvement in tear film and some features of ocular surface such as breakup time of tear film and corneal staining. Patients may suffer from obstruction of Whartons duct or epiphora after surgery. Activation of secretion-related receptors could improve the early hypofunction of the denervated SMG and prevent the duct obstruction. Reduction surgery, partial SMG transplantation, uses of atropine gel or Botulinum toxin A could be the choices of treatment for epiphora.

Clinicopathological characteristics of immunoglobulin G4-related sialadenitis

IntroductionImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition. Forty-two cases with immunoglobulin G4-related sialadenitis (IgG4-RS) confirmed by histopathological and immunohistochemical assessment were studied to clarify the clinicopathologic characteristics of the salivary glands involved in IgG4-RS, especially the relationship between the histopathologic features and function of salivary glands or serum levels of IgG4.MethodsClinical, serologic, imaging and histopathological data of these cases were analyzed. CT volumes of submandibular, parotid, and lacrimal glands were calculated. The saliva flow rate was measured. Scintigraphy with 99mTc-pertechnetate was undertaken in 31 cases, and the concentration index (CI) and secretion index (SI) was calculated. Relationships between fibrosis severity and salivary gland function or serum IgG4 levels were analyzed.ResultsThe first symptom was swelling of bilateral submandibular or lacrimal glands. Physical examination showed multiple bilateral major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands were enlarged in IgG4 RS. Multiple enlarged cervical lymph nodes were noted in 30 patients. Saliva flow at rest was lower than normal in 34 cases; stimulated saliva flow was lower than normal in 15 cases. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in 95.2% of cases and 78.6% patients had increased IgE levels. Serum IgG4 level was higher and saliva secretion lower as glandular fibrosis increased.ConclusionsProminent changes in the morphology, histology, immunohistochemistry and secretion of the major salivary glands of IgG4-RS patients were accompanied by involvement of the lacrimal glands and cervical lymph nodes. Elevated IgE, allergic history, eosinophil infiltration suggest allergic reactions as a potential pathogenesis of IgG4-RS. Severity of glandular fibrosis correlated with salivary function and serum levels of IgG4.

Schirmer test in transplanted submandibular gland: influencing factors and a modified measurement method.

Purpose: To explore a modified Schirmer test for patients with submandibular gland (SMG) transplant. Methods: Thirty-seven patients (39 eyes) with severe keratoconjunctivitis sicca who underwent SMG transplantation in an institutional setting were included. Schirmer test I was performed on each eye under 4 different conditions: (1) Basal condition: a single test at 23°C room temperature after 30 minutes of rest (ST1 results); (2) Physical activity: 6 consecutive tests 0 to 30 minutes after stair climbing (ST2–ST7 results in a time sequence); (3) Glandular massage: 5 consecutive tests 0 to 25 minutes after glandular massage (ST8–ST12 results in a time sequence); and (4) High temperature: a single test at 30°C room temperature (ST13 results). The main outcome measurement was value of Schirmer test. Results: Compared with the basal condition (median ST1 score was 23 mm), physical activity produced increased ST scores within the first 20 minutes (median ST2 to ST5 scores were 73, 69, 39, and 34 mm, respectively, P < 0.01). At the first 10 minutes after glandular massage, median ST8 and ST9 scores were 72 and 18 mm, respectively (P < 0.01). At 30°C room temperature, median ST13 score was 59 mm (P < 0.01), whereas 20 to 30 minutes after physical activity and 10 to 25 minutes after glandular massage, median ST6 to ST7 and ST10 to ST12 scores were 25, 25, 19, 17, and 21 mm, respectively (P > 0.05). Conclusions: A basal condition without physical activity or glandular stimulation at a comfortable and stable room temperature could be considered a standardized condition for Schirmer test for patients with SMG transplant.

Obstructive sialadenitis of a transplanted submandibular gland: chronic inflammation secondary to ductal obstruction

Aims To determine the pathological basis and clinical features of obstructive sialadenitis in transplanted submandibular glands (SMGs). Methods A total of 161 patients (174 eyes) with keratoconjunctivitis sicca underwent microvascular SMG transplantation. Patients were followed up at approximately 1 and 4 months and annually thereafter. Clinical data, including dry eye discomfort, symptoms of ductal obstruction, and Schirmer test, were recorded. Sialography was performed in six patients. In addition, SMG autotransplantation was performed in 22 rabbits. Salivary flow was recorded and the morphology of glands was examined at 6 months postoperatively by light microscopy. Results Among the patients, 16 out of 172 glands during the latent period (0–3 months) and 2 out of 154 glands with long-term follow-up (>1 year) showed obstructive sialadenitis. Typical manifestations were continuous small volumes of viscous secretions, recurrent gland swelling, decreased Schirmer test values, and irregular dilation of the main duct on sialography. The transplanted SMGs eventually showed no secretion in five cases. Of the 22 rabbit SMGs, 4 had obstructive sialadenitis. Morphological examination showed chronic inflammatory infiltration with salivary deposits. Conclusions Obstructive sialadenitis of transplanted SMGs is a chronic inflammation secondary to ductal obstruction, which leads to insufficient ocular lubrication and potential treatment failure.

Comorbid diseases of IgG4‐related sialadenitis in the head and neck region

To further recognize the comorbid diseases of immunoglobulin G4‐related sialadenitis (IgG4‐RS) in the head and neck region and to observe the response of these conditions to immunomodulatory therapy.

Carbachol improves the secretion of transplanted submandibular glands during the latent period after microvascular autologous transplantation for severe keratoconjunctivitis sicca

Poor secretion of transplanted submandibular glands (SMGs) during the latent period may cause duct obstruction and affects the surgical outcome. The objective of this study was to investigate the efficacy and systemic side effects of carbachol on transplanted SMG secretion. Twenty-seven patients who underwent SMG transplantation for severe keratoconjunctivitis sicca were treated with subcutaneous injections of 0.2mg/2ml carbachol at 10 days, 1 month, and/or 3 months after surgery. The effect on secretion was evaluated by Schirmer test and technetium 99m ((99m)Tc) scintigraphy. Systemic side effects were evaluated subjectively using a questionnaire. The results showed that the time to onset varied from 4 to 9min and the duration of action from 50 to 110min after carbachol administration. The secretion at each time point after drug administration was significantly higher than the pre-administration value (all P<0.01). (99m)Tc scintigraphy showed a decline in the dynamic time-activity curve in 26 patients, demonstrating a stimulatory effect on the secretion of carbachol. No serious systemic side effects were experienced. In conclusion, the intermittent administration of carbachol could be an effective and safe strategy to promote secretion from transplanted SMGs in the latent period to prevent duct obstruction.

Effects of Capsaicin and Carbachol on Secretion From Transplanted Submandibular Glands and Prevention of Duct Obstruction.

Purpose: To investigate whether capsaicin and carbachol promote secretion from and prevent duct obstruction in transplanted submandibular glands (SMGs). Methods: This retrospective cohort study included consecutive patients with severe keratoconjunctivitis sicca and successful SMG transplantation. Patients were divided into 2 groups: an exposed group receiving both capsaicin and carbachol after surgery and an unexposed group receiving neither. Secretion changes in response to capsaicin and carbachol administration were recorded in the exposed group. The main outcome measures were the secretory flow rate and duct obstruction rate in the transplanted SMGs. Results: Forty-four patients (44 eyes) in the unexposed group and 115 patients (128 eyes) in the exposed group were followed up for more than 3 months postoperatively. The baseline characteristics were similar between the groups. The secretory flow rate before and 5, 25, 55 minutes after administration was 1 mm (0–2 mm) (median with interquartile range), 3 mm (1–5 mm), 4 mm (2–5 mm), 1 mm (0–2.5 mm), respectively, for capsaicin and 1 mm (0–3 mm), 1050 mm (450–1500 mm), 375 mm (150–600 mm), 0 mm (0–150 mm), respectively, for carbachol (P < 0.001 for both). In the exposed group, 6.2% of eyes had duct obstruction, whereas 18.2% of eyes in the unexposed group had duct obstruction (P = 0.031) (odds ratio = 0.3, 95% confidence interval, 0.105–0.856). Conclusions: This study provides evidence that capsaicin and carbachol effectively promote secretion from and prevent duct obstruction in transplanted SMGs during at least 3 months after transplantation.

Minor salivary glands function is decreased in hyposalivation-related diseases.

OBJECTIVES The aim of this cross-sectional study was to investigate the relationship between minor salivary gland (MSG) flow rates and oral dryness degrees in patients with xerostomia induced by primary Sjögrens syndrome (pSS), IgG4-related sialadenitis (IgG4-RS), radiation therapy-induced dry mouth (RTDM), or Steven-Johnson syndrome (SJS). DESIGN 160 patients with pSS, IgG4-RS, RTDM, or SJS and their age- and sex-matched healthy control subjects were enrolled. The whole saliva flow rates and MSG flow rates were measured in four locations, including the upper labial, lower labial, buccal, and palatal mucosae. The degree of oral dryness was assessed in patient groups using the summated xerostomia inventory (SXI). RESULTS The flow rates of whole saliva and most MSGs in patient groups were significantly lower than the flow rates in healthy control groups (P<0.05). The mean relative percentage of decrease in saliva flow rates was smaller in MSGs than in whole saliva in patient groups (P<0.05), indicating that these disorders have less impact on MSGs. Among the four MSG locations (the upper labial, lower labial, buccal, and palatal), buccal glands showed the highest flow rates in patient groups (P<0.05). SXI scores were significantly higher in pSS and RTDM patients than in IgG4-RS and SJS patients (P<0.05). The degree of xerostomia varied among different patient groups (P<0.05) and there was no clear correlation between MSG flow rates and SXI scores (P>0.05). CONCLUSIONS MSG function is significantly reduced in pSS, RTDM, IgG4-RS, and SJS patients, but this reduction is more pronounced in the major salivary glands.

Differential diagnosis of IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis

Our aim was to differentiate IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis by analysing clinical, radiographic, and pathological features. Fifty-five patients, 50, and 50 were enrolled, respectively and their baseline characteristics and serological, sialographic, and pathological findings compared. The male:female ratio for IgG4-related sialadenitis was 1:1.2 for primary Sjögren syndrome 1:15.7, and for chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and 0 (p=0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9) g/L, and 5.3 (1.6) g/L, p<0.001 in all cases. Sialography showed enlargement of the gland, dilatation of the duct, and slightly decreased secretory function in IgG4-related disease; obvious sialectasia and decreased secretory function in Sjögren syndrome; and dilatation of Whartons duct and filling defects in obstructive sialadenitis. Histopathological examination showed lymphoplasmacytic infiltration with storiform fibrosis, lymphoplasmacytic inflammation and lymphoepithelial lesions, and dilatation of the duct with epithelial metaplasia in the three groups, respectively. The number of IgG4-positive plasma cells was 123 (45)/HPF, 8 (3)/HPF, and 5 (4)/HPF, while the IgG4-/IgG-positive cell ratio was 71.7 (13.9)%, 4.6 (2.5)%, 18.9 (19.7)%, respectively (p<0.001). The three conditions have different clinical, radiographic, and pathological features that provide important clues to the differential diagnosis. Serological and histological tests are important, and comprehensive consideration is necessary.