Now Reading
Chymotrypsin with sialendoscopy-assisted surgery for the treatment of chronic obstructive parotitis

Chymotrypsin with sialendoscopy-assisted surgery for the treatment of chronic obstructive parotitis



International Journal of Oral & Maxillofacial Surgery, 2017-07-01, Volume 46, Issue 7, Pages 877-882, Copyright © 2017 International Association of Oral and Maxillofacial Surgeons


Abstract

Chronic obstructive parotitis (COP) is a common disease of the parotid gland. A total of 104 patients with COP were identified and randomized into a treatment group (52 cases) and a control group (52 cases). All patients underwent sialography and salivary gland scintigraphy (SGS) examinations before surgery. The patients in the treatment group received chymotrypsin combined with gentamicin via interventional sialendoscopy to irrigate the duct, and the control group received gentamicin alone. All patients were asked to record their pain on a visual analogue scale (VAS) before treatment and at 1 week, 2 weeks, 1 month, 3 months, and 6 months after surgery. The VAS score for pain intensity was decreased at 1 week post-treatment in both groups ( P < 0.05). Compared to the control group, the VAS score was lower in the treatment group at 1 week, 2 weeks, and 1 month post-treatment ( P < 0.05). The 6-month postoperative SGS results showed improved uptake and excretion in both groups ( P < 0.05). The treatment group exhibited higher scores for postoperative SGS excretion than the control group ( P < 0.05). The administration of chymotrypsin combined with gentamicin by sialendoscopy is effective for the treatment of non-stone-related COP and specifically improves the excretion function of the parotid gland.

Chronic obstructive parotitis (COP) is a common non-neoplastic disease that is characterized by recurrent parotid swelling and pain and may be aggravated while eating in some patients . This disorder generally results from local factors, such as sialolithiasis, stricture, kinks, mucus plugs, polyps, and foreign bodies. The common diagnostic approach for COP consists of ultrasound, computed tomography, sialography, and salivary gland scintigraphy (SGS) examinations ; however, these methods do not allow the direct visualization of the inner duct system to determine the cause of the ductal obstruction.

Among the endoscopic techniques that have been used widely in the diagnosis and treatment of various diseases, sialendoscopy has become a gold standard for the diagnosis of chronic obstructive sialadenitis . Sialendoscopy can provide direct visualization of the ductal system of the parotid glands, allowing the identification of factors causing an obstruction, as well as the irrigation of the duct with drugs, and can simultaneously facilitate the removal of stones. Many drugs can be used for irrigation, such as methyl violet, hyaluronidase, iodized oil, chloramphenicol, gentamicin, and dexamethasone. Chymotrypsin is a proteolytic enzyme extracted from the bovine or porcine pancreas that can decompose peptide chains and solubilize proteins, thereby promoting the dissolution and decomposition of purulent secretions and necrotic tissues. The use of chymotrypsin for clinical applications has been affirmed in the fields of ophthalmology and dermatology . The aim of this study was to evaluate the clinical effects of chymotrypsin combined with gentamicin administered via sialendoscopy for the treatment of COP.

Materials and methods

Approval for this study was obtained from the institutional review board of the China Medical University. All participants signed an informed consent agreement. All of the guidelines and protocols of the Declaration of Helsinki were followed during the course of the study.

Study design

A total of 104 patients (168 glands) with COP who attended the Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University (Shenyang, China) between June 2014 and December 2015, were selected for inclusion in this study. Patients were diagnosed with COP based on history, clinical manifestations, and a series of diagnostic methods including ultrasound, SGS examination, sialography, and sialendoscopy. Patients with diseases such as tumours and sialolithiasis diagnosed based on ultrasound findings were excluded. After SGS examination and sialography, patients diagnosed with chronic recurrent parotitis or Sjögren’s syndrome were also excluded. Furthermore, patients found to have negative stones, polyps, and foreign bodies under sialendoscopy were excluded.

After obtaining written informed consent, 104 patients meeting the necessary criteria were assigned randomly to two groups using a random number sealed-envelope system: 52 patients to the treatment group and 52 patients to the control group. Both the surgeon and the patient were blinded to the study group assignment.

Operative procedure

All patients underwent preoperative sialography and SGS examinations to exclude surgical contraindications and patients who were allergic to chymotrypsin. During surgery, a set of specialized probes (size 00 to 3) was used to dilate the natural opening of the parotid. Sialendoscopy (PolyDiagnost GmbH, Hallbergmoos, Germany) was then performed ( Fig. 1 ). The probe was 1.1 mm in diameter and had a working channel of 0.55 mm in diameter.

Sialendoscopy was performed through Stensen’s duct.
Fig. 1
Sialendoscopy was performed through Stensen’s duct.

In the treatment group, 5 mg of chymotrypsin and 80,000 units of gentamicin were mixed with 25 ml of sterile saline solution and injected into the duct through the irrigation channel of the endoscope until most of the fibre-like substances had disappeared from the field of view ( Fig. 2 a, b). The liquid mixture was retained in the parotid gland for approximately 3 to 5 min after removal of the endoscope. Pressure was then applied to the parotid region until clear liquid flowed out of the parotid duct. The control group patients received 80,000 units of gentamicin mixed with 25 ml of sterile saline solution to irrigate the duct. All patients in this study were asked to record their pain level on a visual analogue scale (VAS) before the operation and at 1 week, 2 weeks, 1 month, 3 months, and 6 months after the operation.

(a) Mucus plugs and fibre-like substances were observed via sialendoscopy. (b) A mixture was injected into the ducts through the irrigation channel of the endoscope until most of the fibre-like substances had disappeared from the field of view.
Fig. 2
(a) Mucus plugs and fibre-like substances were observed via sialendoscopy. (b) A mixture was injected into the ducts through the irrigation channel of the endoscope until most of the fibre-like substances had disappeared from the field of view.

Evaluation of the results

The VAS score was used to evaluate clinical symptoms including pain and swelling of the parotid gland before and after treatment. The VAS consisted of a 0–10 cm scale that was used to express the degree of clinical symptoms as manifested by a combination of pain and swelling, with 0 representing no clinical symptoms and 10 representing unbearable clinical symptoms.

SGS examinations were used for the quantitative evaluation of uptake and excretion in the salivary glands before and 6 months after the operation. The patient was injected intravenously with approximately 370 MBq (10 mCi) of 99m Tc-pertechnetate and salivary gland scintigraphy was performed for 30 min with single photon emission computed tomography (SPECT). Vitamin C (0.2 g) was administered orally at 20 min to stimulate salivary gland excretion. The mean functional parameters of the bilateral parotid and the submandibular glands were calculated according to the radioactive count and the corresponding time for the evaluation of salivary gland function.

Data analysis

IBM SPSS Statistics version 19.0 software (IBM Corp., Armonk, NY, USA) was used for the data analysis. Comparisons of the VAS scores and SGS results of each group before and after surgery were performed using a paired t -test. The difference in the treatment effect between the two patient groups was compared using an independent samples t -test. A P -value of less than 0.05 was considered statistically significant.

Results

The patients in the treatment group (18 male and 34 female) ranged in age from 29 to 72 years, with a mean age of 47.1 years. The disease duration ranged from 3 to 48 months (mean 8.4 months). The patients in the control group (19 male and 33 female) ranged in age from 25 to 70 years, with a mean age of 48.2 years. The disease duration ranged from 2 to 50 months (mean 8.8 months). The differences between the two groups with regard to sex, age, and average disease duration were not statistically significant ( P > 0.05) ( Table 1 ).

Table 1
Basic patient characteristics.
Treatment group
( n = 52)
Control group
( n = 52)
Sex, n
Male 18 a 19
Female 34 a 33
Age (years), mean ± SD 47.10 ± 8.56 a 48.21 ± 9.12
Disease duration (months), mean ± SD 8.4 ± 7.3 a 8.8 ± 7.4
SD, standard deviation.

a P > 0.05, compared to the control group.

Varying degrees of stenosis and expansion of the main parotid duct and branches were found via preoperative sialography in the patients in this study; some exhibited typical sausage-like images ( Fig. 3 ). SGS examinations showed normal or slightly decreased uptake and considerably decreased excretion ( Fig. 4 a). Hyperemia of the ductal wall ( Fig. 5 ), mucus plugs, and fibre-like substances ( Fig. 6 ) were also detected via sialendoscopy.

Varying degrees of stenosis and expansion of the main parotid duct and branches were observed via preoperative sialography; some cases exhibited typical sausage-like images.
Fig. 3
Varying degrees of stenosis and expansion of the main parotid duct and branches were observed via preoperative sialography; some cases exhibited typical sausage-like images.

(a) Salivary gland scintigraphy showed normal or slightly decreased uptake and considerably decreased excretion. (b) The postoperative uptake ratio (UR15) and excretion fraction after 6 months were significantly higher than the preoperative uptake ratio and excretion fraction.
Fig. 4
(a) Salivary gland scintigraphy showed normal or slightly decreased uptake and considerably decreased excretion. (b) The postoperative uptake ratio (UR15) and excretion fraction after 6 months were significantly higher than the preoperative uptake ratio and excretion fraction.

Hyperemia of the ductal wall.
Fig. 5
Hyperemia of the ductal wall.

Fibre-like substances.
Fig. 6
Fibre-like substances.

No significant differences were observed in the preoperative VAS scores between the two groups ( P > 0.05). The 1-week postoperative VAS scores were significantly lower than the preoperative VAS scores in both groups ( P < 0.05). The postoperative VAS scores in the treatment group at 1 week, 2 weeks, and 1 month after the procedure were significantly lower than those in the control group ( P < 0.05). However, no significant difference was found in the postoperative VAS scores between the two groups after 3 months or 6 months ( P > 0.05) ( Table 2 ).

Table 2
VAS scores of the two groups of patients before and after surgery.
Observation time point Treatment group
( n = 52), mean ± SD
Control group
( n = 52), mean ± SD
Before treatment 6.12 ± 0.96 6.08 ± 1.02
After treatment
1 week 2.63 ± 1.07 a,b 3.13 ± 1.28 a
2 weeks 1.63 ± 0.84 b 2.35 ± 0.86
1 month 1.10 ± 0.85 b 1.62 ± 0.97
3 months 0.77 ± 0.76 1.08 ± 0.93
6 months 1.23 ± 1.17 1.54 ± 1.45
VAS, visual analogue scale; SD, standard deviation.

a P < 0.05, compared to the VAS score before surgery.

b P < 0.05, compared to the control group.

No significant difference was observed in the preoperative SGS results between the two groups ( P > 0.05). The postoperative uptake ratio (UR15) and excretion fraction (EF) after 6 months were significantly higher than the preoperative UR15 and EF in both groups ( P < 0.05) ( Fig. 4 b). The difference between the preoperative and postoperative EF in the treatment group was significantly higher than that in the control group ( P < 0.05). The difference between the preoperative and postoperative UR15 in the treatment group did not differ significantly from that of the control group ( P > 0.05) ( Table 3 ).

Table 3
SGS results of the two groups of patients before and after surgery.
Treatment group
( n = 52), mean ± SD
Control group
( n = 52), mean ± SD
Uptake ratio (%) c
Before 1.50 ± 0.51 1.43 ± 0.43
6 months after 1.63 ± 0.52 a 1.55 ± 0.47 a
Difference 0.13 ± 0.13 0.12 ± 0.12
Excretion fraction (%) d
Before 53.08 ± 11.50 52.91 ± 11.33
6 months after 58.63 ± 11.17 a 57.09 ± 12.07 a
Difference 5.55 ± 3.12 b 4.19 ± 3.03
SGS, salivary gland scintigraphy; SD, standard deviation.

a P < 0.05, compared to the SGS results before surgery.

b P < 0.05, compared to the control group.

c Normal range in the parotid gland, 1.48–3.88; normal range in the submandibular gland, 1.72–3.38.

d Normal range in the parotid gland, 74.18–87.00; normal range in the submandibular gland, 52.32–76.46.

Discussion

The principles of treatment of COP consist of removing the cause of the obstruction and relieving the clinical symptoms. Traditional treatments for COP include conservative treatments such as massaging the parotid gland, gargling with warm saline water, eating acidic foods to stimulate saliva secretion, irrigating with antibiotics, and surgical treatments including the removal of calculus, duct ligation, superficial parotidectomy, total parotidectomy, and near-total parotidectomy . In patients with non-stone-related COP, the most common treatment is parotid duct dilation and drug irrigation therapy. Many drugs can be used for irrigation, such as methyl violet, hyaluronidase, iodized oil, chloramphenicol, gentamicin, and dexamethasone. Conservative treatments are unable to cure COP due to the aetiology; furthermore, a long course of treatment, uncertain efficacy, and recurrent disease are painful for patients. Surgical treatment, such as a parotidectomy at the expense of gland function, can easily cause facial nerve damage and scarring.

SGS is a simple, non-invasive, and accurate method to assess the functional state of the gland. SGS can be used to assess not only the location, shape, and size of the salivary glands, but also to quantitatively evaluate the uptake and excretion of the salivary glands. The results are not affected by differences in patients or operators, who can fully and objectively evaluate lesions of the salivary gland . Compared to sialography, SGS can quantitatively evaluate the uptake and excretion of the parotid and submandibular glands, providing valuable reference information for clinical diagnosis. In addition, SGS is relatively painless and is convenient for the patient . All patients in this study were subjected to ultrasound to exclude the presence of tumours and stones, and SGS was performed to exclude patients with severely damaged parotid gland excretion and Sjögren’s syndrome, as well as a diagnosis of COP after sialography. Patients underwent SGS 6 months after the operation to compare the differences in uptake and excretion in the salivary glands before and after surgery and the differences in treatment effects between the two groups.

Starting in 1994, Nahlieli et al. and Marchal et al. designed sialendoscopy and related equipment specifically for salivary duct obstruction diseases according to the anatomical characteristics of the salivary glands, allowing a diagnosis of the aetiology to be made, as well as the provision of minimally invasive treatment for these diseases. Using sialendoscopy, practitioners can clearly observe the changes in the salivary ductal structure and simultaneously perform minimally invasive treatments with fewer surgical complications, thereby reducing patient anxiety and pain.

Many causes of ductal obstruction have been postulated since the introduction of sialendoscopy, such as mucus plugs, fibre-like substances, polyps, and negative stones . Most patients in this study were found to have hyperplasia and hyperemia of the ductal wall, and some patients exhibited mucus plugs and fibre-like substances via sialendoscopy. Qi et al. extracted the irrigation liquid from the glands of patients with COP for examination under light microscopy; they found that the fibre-like substances were composed of desquamative duct epithelial cells, neutrophils, lymphocytes, and acidophils . Hyperemia of the ductal wall and the fibre-like substances adhering to the wall are diagnosed as ductal inflammation. The inflammatory exudate in the lumen wall forms fibre-like substances, followed by the formation of adhesions in the ductal lumen, resulting in different degrees of blockage. Mucus plugs often coexist with duct inflammation and are observed via sialendoscopy. The secretion of ductal lumen retention causes the saliva to become muddy and sticky after secondary infection, ultimately leading to the formation of a mucus plug. Calculus is also a common reason for obstruction; the causes and mechanisms of the formation of calculus are unclear, but mucus plug and calculus formation may be related .

Sialendoscopy-assisted drug irrigation has two roles. First, a large amount of liquid is used to fill the duct so that the sialendoscopy instruments can easily move within the ductal lumen without damaging the duct wall. A clear image of the ductal lumen can be obtained while the liquid is being injected. Second, a large volume of continuous drug irrigation removes fibre-like substances, mucus plugs, or other inflammatory products within the duct, eliminating the local source of infection, to ensure the effects of treatment.

Chymotrypsin can decompose mucus plugs, fibre-like substances, and inflammatory secretions within the parotid duct and increase tissue permeability, improve microcirculation, inhibit inflammation, and reduce oedema. At the same time, the viscosity of saliva is reduced, promoting saliva flow and reducing the accumulation of local inflammation. Chymotrypsin (5 mg) is dissolved in 25 ml of sterile saline to form a 1:5000 mixture; chymotrypsin is most active at pH 7–8, and a temporary preparation can fully guarantee its efficacy. This concentration is also used in ophthalmic cataract surgery. Gentamicin is a broad-spectrum aminoglycoside antibiotic with a stable performance, low irritation, and no skin test requirement. Irrigation of the parotid gland with gentamicin can kill pathogenic bacteria within the main ducts or branches. The simultaneous application of chymotrypsin and gentamicin can enable the antibiotic to penetrate the sites of inflammation, improving the synergy and clinical efficacy of the two drugs.

The patients in this study were monitored for 6 months after surgery. The results were assessed by VAS scores and SGS results. After 1 week, 2 weeks, 1 month, and 3 months, the VAS scores in both groups gradually declined, indicating that symptoms were improved after surgery in both groups. The postoperative VAS scores after 1 week, 2 weeks, and 1 month in the treatment group were significantly lower than those in the control group, which indicates that chymotrypsin combined with gentamicin has better short-term efficacy. However, the VAS scores increased after 6 months, which may be related to the duration of drug efficacy; this finding also indicates that COP is likely to relapse. The postoperative UR15 and EF after 6 months were significantly higher than the preoperative UR15 and EF in both groups, indicating that the uptake and excretion functions of the parotid glands improved after surgery in both groups. The difference between the preoperative EF and the postoperative EF was significantly higher in the treatment group than in the control group, indicating that chymotrypsin combined with gentamicin significantly improved parotid gland excretion function.

Theoretically, there is a risk of duct wall perforation, bleeding, and nerve damage during surgical procedures with sialendoscopy. If the operator causes trauma due to inexperience, the trauma can cause the ductal lumen to become narrow again. Therefore, the operator should be cautious and should not be forceful. Swelling and discomfort of the glands is a common complication of sialendoscopy surgery. The swelling gradually disappears as the liquid drains after a few hours. The 104 patients in this study exhibited different degrees of postoperative swelling of the parotid glands, and extract of horse chestnut seed tablets (0.8 g) were taken orally twice daily to relieve the swelling after surgery.

The limitations of this study must be taken into consideration. The number of patients included in this study was small and the follow-up period was not sufficiently long. Further studies with longer follow-up durations are needed to evaluate the clinical effects of chymotrypsin combined with sialendoscopy-assisted surgery for the treatment of COP.

In summary, treatment with a combination of chymotrypsin and gentamicin via sialendoscopy is effective for non-stone-related COP and specifically improves the excretion function of the parotid glands. This technique provides a new approach for the treatment of non-stone-related COP.

You're Reading a Preview

Become a DentistryKey membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here