A Single-arm, Single-center Clinical Study of Endoscopic Combined With Intraoperative Navigation-assisted Treatment of Giant Mandibular Cysts
Phase: NA
Conditions: Jaw Cysts
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Clinical study protocol
Project name: Single-arm, single-center clinical study of endoscopy
combined with intraoperative navigation-assisted treatment of giant
mandibular bone cysts
Sponsor: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Version number: V5.0
Version date: 2024-05-25
Project Leader: Wang Yan
Plan signature confirmation:
_______________________________________________________
Statement of compliance
Comply with the provisions of the Good Practice for the Quality Management of Clinical Trials for
Drugs and the Measures for the Management of Investigator-Initiated Clinical Studies in Healthcare
Institutions (Trial) and the Declaration of Helsinki, and commit to conduct this study in accordance
with this protocol, participants must be trained to conduct the study after obtaining written approval of
the Ethics Committee and written informed consent of the subject, The revised plan needs to be
re-approved.
___________________________________________________________________________________

I. Program summary
In this study, with the assistance of endoscopic technology and intraoperative
navigation technology, the removal and curettage of large odontogenic jaw cyst
occurred in the mandible were performed to reduce the rate of postoperative nerve
injury. A series of complications, such as residual lesion, pathological fracture, nerve
injury and so on, were caused by the enlargement of incision due to limited visual
field and the doubt in determining the boundary of cyst. In this study, endoscopic
technique enabled the surgeon to obtain sufficient field of view in small incision,
better understand the characteristics of the lesion, protect the inferior alveolar
neurovascular bundle, prevent intraoperative pathological fracture and shorten the
operation time. The intraoperative navigation technology allows doctors to accurately
locate the anatomical positions of each bone in the maxillofacial region, and the
navigation probe can accurately judge each orientation of the sac cavity. At the same
time, the adapter is used to integrate the navigation and endoscopy, so that the
endoscope can not only play the role of obtaining a clear vision but also play the
function of real-time positioning. In this study, we compared the efficacy of
traditional extraction and curettage with endoscopic navigation assistance in the
treatment of giant mandibular bone cysts. In this study, the rate of inferior alveolar
nerve injury 1 month after surgery was taken as the main outcome index, and the
recurrence rate 1 year after surgery was taken as the secondary outcome index, to
explore
whether
endoscopic
combined
with
intraoperative
navigation-assisted
treatment of giant mandibular bone cyst could achieve lower postoperative nerve
injury rate and postoperative recurrence rate.
II. Introduction
2.1 Research theoretical basis/background
Odontogenic jaw cyst is a unique disease affecting the mouth and mandible. Its
occurrence is closely related to the development and formation of dental tissue and
inflammation. The four most common odontogenic jaw cysts include periapical cyst,
odontogenic cyst, residual cyst, and odontogenic keratosis cyst1. Most cysts grow
slowly and may have only mild or no symptoms. When cysts grow larger, they can
damage the surrounding tissue, leading to maxillofacial swelling, infection, root
resorption, nerve damage, pathological fracture, and even malocclusion2. Smaller
odontogenic jaw cysts can be removed directly by surgery, while the treatment of
larger odontogenic jaw cysts remains controversial. Some scholars believe that
fenestration decompression is an effective and conservative treatment3, but some
scholars believe that although fenestration decompression is less traumatic, patients
will be accompanied by discomfort during the long healing period, and direct surgery
to remove the complete lesion is the best choice4.
In a previous retrospective study of 25 patients with large mandibular cysts who
underwent traditional removal and curettage surgery, 8 patients developed symptoms
of nerve damage after surgery, with a postoperative nerve damage rate of up to 32%.

It can be seen that how to effectively reduce the rate of nerve damage after surgery for
giant mandibular bone cysts is still a difficult problem5. Related retrospective studies
have shown that most jaw cysts occur in the anterior maxilla and molar areas of the
mandible, and odontogenic jaw cysts are common in the mandibula6. When the cyst
lesion involves the mandibular branch, due to the high anatomical position, the
surgeon cannot observe the full scope of the lesion under direct vision, and it is
difficult to accurately locate the lesion boundary, which will increase the risk of
residual lesion and postoperative recurrence, and bring difficulty and challenge to the
operation. In addition, the inferior alveolar nerve passes through here, and if the
location relationship between the nerve and the lesion is not clear, the risk of nerve
injury will be greatly increased. When odontogenic maxillary cysts involving
mandibular branches cannot be completely observed under direct vision, endoscopic
techniques enable the surgeon to obtain sufficient visual field through small
incisations, better understand the characteristics of the lesions, protect the inferior
alveolar neurovascular bundles, prevent intraoperative pathological fractures and
shorten the operation time 8-10.
Although endoscope can help surgeons to clearly observe lesions and nerves, it
cannot standard determine the anatomical position of each bone in maxillofacial
region, the boundary of lesions and the anatomical relationship between lesions and
nerves. Navigation technology provides a solution to this problem. In order to apply
navigation technology in the operation, it is necessary to collect the data of the
patient's lesion site before surgery, conduct 3D simulation and establish a model to
clarify the anatomic relationship between the lesion and the surrounding tissue11.
During the operation, the reference frame should be fixed in the mandible, and the
anatomical position of each bone in the maxillofacial region and the boundary of the
lesion should be accurately located by the locator and probe, and the area reached by
the probe or surgical instrument should be reflected in real time, so that the surgeon
can accurately judge each orientation of the sac cavity 12-14, and play a role in guiding
the surgical route.
However, there are few studies on endoscopy combined with intraoperative
navigation-assisted treatment of giant mandibular bone cysts. In this study, an
innovative surgical scheme will be proposed to integrate endoscopy and navigation
through the adapter, so that endoscopy can not only play the role of obtaining a clear
vision but also play the function of real-time positioning, so as to achieve accurate
surgery, aiming at reducing the postoperative nerve injury rate and postoperative
recurrence rate of odontogenic jaw cyst, so as to obtain better clinical efficacy.
2.2 Risk/benefit evaluation
2.2.1 Known potential risks
(1) Accidental risk of general anesthesia: After patients receive general anesthesia,
due to individual differences of patients, abnormal response to drugs may lead to
severe
suppression
of
respiratory
and
circulatory
functions
and
malignant
hyperthermia, etc., which can be life-threatening in severe cases. During anesthesia,
various adverse reflexes may induce cardio-cerebrovascular accidents or cardiac and

respiratory arrest, leading to death. In the event of anaesthesia related adverse
reactions, clinical treatment should be performed as a complication of normal surgery,
while the patient's medical record is detailed and the possibility of continuing the
clinical trial should be evaluated.
(2) Risk of tearing the inferior alveolar neurovascular bundle: When cystic lesions are
severely attached to the nerve, there is a risk of nerve tearing when separating the
mass, resulting in postoperative damage to the inferior alveolar nerve and numbness
of
the
lower
lip.
When
intraoperative
nerve
tears
occur,
intraoperative
neuroanastomosis should be performed to preserve nerve function as much as
possible.
(3) Risk of serious infection after surgery: When the scope of cystic lesions is too
large, the risk of postoperative infection increases, and the wound in the operative
area may not heal in one stage. In severe cases, it may spread to neighboring tissues,
resulting in infection of the maxillofacial space. In the case of severe infection,
anti-infection treatment should be actively applied. In the case of infection of
maxillofacial space or severe edema of surrounding tissue, the existence of indications
for incision and discharge of pus should be considered, and the vital signs of patients
should be closely monitored.
(4) In this study, for patients with serious complications of anesthesia during
perioperative period, severe postoperative infection or bleeding, respiratory distress
caused by severe edema of surrounding tissues, and failure to reanastomosis of nerve
tear, etc., the study intervention should be suspended and withdrawn from the study,
clinical treatment of corresponding complications should be carried out, and patients
should be actively treated. Specific measures should be the treatment plan mentioned
in the above complications. The safety of the surgical method of the study protocol
was discussed, and the follow-up was determined whether to adjust the study surgical
protocol, and follow-up records of the original subjects were maintained during the
suspension of the study. In the case of clear withdrawal, the investigator may continue
to complete the follow-up without the study intervention.
2.2.2 Known potential benefits
The potential benefits of this study include safer and more effective surgery,
complete curettage of cystic lesions and protection of the associated normal
anatomical structure. It can better protect lower alveolar neurovascular bundle,
prevent intraoperative pathological fracture and shorten operative time. The operation
is minimally invasive and the patients recover faster after operation. Subjects entering
this clinical study can reduce the surgical cost of endoscopic technology, gain more
attention from researchers and timely treatment of disease changes, which is
conducive to the treatment of subjects' diseases.
2.2.3 Potential risk and benefit evaluation
In this study, endoscopy combined with intraoperative navigation assisted
treatment of giant mandibular bone cysts was adopted. Endoscopy technology
provided surgeons with a clearer and more complete surgical field of view, while

navigation technology could reflect the relationship and position between surgical
instruments and the patient's anatomical structure in real time, allowing surgeons to
obtain clear and objective anatomical recognition during surgery. Preoperative
computer simulation combined with intraoperative navigation has been proven to be
an effective way to improve surgical outcomes. In this study, endoscopic techniques
combined with intraoperative navigation techniques were used to treat large
odontogenic maxillary cysts involving mandibular branches, which were not only safe
and effective, but also able to completely curettage cystic lesions during the operation
and protect the associated normal anatomical structures. It can better protect the lower
alveolar neurovascular bundle, prevent intraoperative pathological fracture and
shorten the operation time. This procedure is minimally invasive and patients recover
faster after surgery. As a result, patients have a lower risk of developing nerve tears
during surgery. In addition, each patient will undergo various basic examinations
before surgery to strictly evaluate whether they can tolerate general anesthesia surgery
and reduce the risk of anesthesia accidents. In future studies, researchers will pay
more attention to the subjects' systemic conditions and tumor treatment, and the
subjects will also obtain certain clinical benefits in this study.
III. Purpose and endpoint of the study
3.1 Purpose
3.1.1 Main purpose
The main objective of this study was to investigate the rate of lower alveolar
nerve
injury
1
month
after
endoscopy
combined
with
intraoperative
navigation-assisted treatment of giant mandibular cyst.
3.1.2 Secondary Purpose
The secondary objective of this study was to investigate the recurrence rate 1
year after endoscopy combined with intraoperative navigation-assisted treatment of
giant mandibular bone cysts.
3.1.3 Exploratory purpose
The exploratory objective of this study was to evaluate the postoperative efficacy
of endoscopy combined with intraoperative navigation-assisted treatment of giant
mandibular bone cysts
3.2. Research indicators
3.2.1 Main Indicators and Definitions
Rate of inferior alveolar nerve injury 1 month after surgery: For patients who
received endoscopic combined with intraoperative navigational assistance in the
treatment of giant mandibular cyst, inferior alveolar nerve function was detected
before surgery and 1 month after surgery to determine whether postoperative inferior
alveolar nerve injury existed. Detailed detection methods are shown below.

3.2.2 Secondary indicators and definitions
Recurrence rate 1 year after surgery: The number of patients who received
endoscopy combined with intraoperative navigation-assisted treatment for giant
mandibular bone cysts who had cyst recurrence 1 year after surgery.
3.2.3 Security Specifications
The subjects' vital signs, blood routine, liver function, heart function, blood
biochemistry, urine routine, stool routine, coagulation function, electrocardiogram,
chest film, maxillofacial imaging data and other safety indicators were all interpreted
by the researcher team based on the test results before the subjects were enrolled.
IV. Study the population
4.1 Inclusion criteria
(1) Aged between 18 and 75 years old
(2) Imaging and puncture pathology showed dental cystic lesions of the mandible
(3) Cystic lesions greater than or equal to 2cm in diameter and affecting the inferior
alveolar nerve
(4) Lesions of new or recurrent cysts, or odontogenic cystic lesions that are still
greater than or equal to 2cm after other treatments such as fenestration and affecting
the lower alveolar nerve
(5) No serious systemic diseases, can tolerate general anesthesia
(6) Patients who intend to undergo surgical treatment for mandibular bone cysts under
general anesthesia
(7) There was no inferior alveolar nerve injury before operation
(8) Did not participate in other clinical trials within the past 30 days
(9) Patients who voluntarily participate in the project and sign informed consent
4.2 Exclusion Criteria
(1) The patient has serious systemic disease or pregnancy, and after the research team
and multidisciplinary consultation and evaluation, it is determined that she cannot
tolerate the clinical study process and general anesthesia
(2) Unable to complete the entire clinical research process due to personal, social and
economic reasons
(3) Patients suffering from mental diseases or unable to perceive and communicate
normally, such as schizophrenia, claustrophobia, etc., are unable to complete the
examination and cooperate with the entire clinical study process
4.3 Lifestyle considerations
After entering the clinical study, the subjects should have a light diet, abstain
from tobacco and alcohol, and prohibit strenuous exercise. If the subjects need to use
drugs, treatments or operations unrelated to the study in the clinical study, the
researchers should evaluate whether the reasons for the need for such drugs,
treatments and surgical treatments are adverse events caused by the study. If the
subject needs additional treatment due to accident or other reasons, whether the

treatment has an impact on the progress of the study will be considered. If the impact
is too large, it is recommended that the subject withdraw from the conventional
treatment and seal the subject's data.
4.4 Filtering Failure
Patients will be screened after signing the informed consent for this study, and
those who fail the screening will be excluded from the study. Based on the results of
the multidisciplinary consultation, the study will inform the failed patients and give
the optimal treatment recommendations.
4.5 Recruitment and retention strategies
This study will recruit subjects mainly offline and combine both online and
offline. The main offline location will be the Oral and maxillofacial Surgery
Department of Sun Yat-sen Memorial Hospital, including but not limited to posters,
leaflets, information sessions and other forms to attract more subjects. Every
interested patient will register on the spot, leave his contact information and continue
to have one-to-one explanation program. If the subject has financial difficulties, the
researcher team will assist the subject to apply for public welfare fund to help reduce
the financial burden of the subjects.
V. Research design
5.1 Overall Design
This
study
hypothesized
that
endoscopy
combined
with
intraoperative
navigation-assisted treatment of giant mandibular bone cysts was more effective than
the traditional surgical method of removal and curettage. In this study, a prospective,
single-arm, Phase II clinical study was used to design the protocol, and the estimated
rate of postoperative nerve injury was reduced by about 12% from 32% to 20%
compared with traditional surgery.
5.2 Research and design process
5.2.1 Study the specific implementation process
This study started from the recruitment of subjects, oral panoramic film,
maxillofacial CT and other imaging examinations were performed to confirm the
diagnosis. After preliminary screening according to the inclusion and exclusion
criteria, patients were enrolled after signing the informed consent letter. Endoscopic
and navigational techniques were used for surgical treatment. This study referred to A
prospective study by Abdullah Hanfesh15 et al to evaluate the function of the inferior
alveolar nerve: the bilateral mandibular and lower lip were divided into four areas:
area A, area B, area C, and area D. The four areas will be lightly touched, acupuncture,
cold and hot stimulation, and two-point discrimination detection four times
respectively. The detection situation of each area will be recorded. The scoring criteria
for each test are as follows.

Figure 1. Area diagram15
A: Upper right lip
B: Upper left lip
C: Right jaw
D: Left mandible
Light touch: Cotton wool is used for light touch detection. The score range is 0-4,
with 4 indicating no nerve damage.
Table 1 Light touch stimulus rating table
Sign
Score
Completely unresponsive to stimuli
0
Severe loss of perception
1
Mild irritation is almost imperceptible
2
Compared with pre-operation
slight stimulation can still be perceived
3
Compared with pre-operation
there was no difference,
normal perception of mild stimulation
4
Acupuncture: Detection is performed using dental probe stimulation on a scale of 0-1,
with 1 indicating no nerve damage.
Table 2. Acupuncture stimulation rating table
Sign
Score
Completely unresponsive to stimuli
0
Produces a sharp tingling sensation to stimuli
1

Figure 2 Lower alveolar nerve function measured by cotton wool15
Figure 3. The function of inferior alveolar nerve was detected by acupuncture15
Hot and cold stimulation: Test tubes filled with hot water (45-50 ° C) and filled with
ice water were used to detect hot and cold stimulation, respectively. The score range
was 0-1, with 1 indicating no nerve damage.
Table 3. Cold and heat stimulation rating table
Sign
Score
Completely unresponsive to stimuli
0
Develop a cold/hot sensation to stimuli
1
Figure 4. The function of inferior alveolar nerve was measured
by heat and cold stimulation15

Two-point discrimination test: The distance between two points can be distinguished
using a vernier caliper. The score ranges from 0 to 5, with 5 indicating no nerve
damage.
Table 4: Two-point discrimination measurement rating table
Sign
Score
The distance between the two ends of
the vernier caliper is > 15mm
0
The distance between the ends of
the vernier caliper is 10-15mm
1
The distance between the ends of
the vernier caliper is 9-10mm
2
The distance between the ends of
the vernier caliper is 7-9mm
3
The distance between the ends of
the vernier caliper is 5-7mm
4
The distance between both ends of
the vernier caliper is less than 5mm
5
Figure 5 Vernier calipers measure the distance between two points15
Inferior alveolar nerve function was detected before and 1 month after surgery.
Light touch detection 4 points, acupuncture detection 1 point, hot and cold stimulation
1 point, two-point discrimination detection 5 points showed no nerve damage. Any
other score for any of the above is considered to be nerve damage.

5.2.2 Study flow charts
122 people were recruited and informed consent was signed.Diagnosis was
made according to imaging, and subjects were screened according to inclusion
and exclusion criteria.
↓
The medical history, imaging data and test results of the subjects were collected.
Baseline assessment was performed to determine whether subjects tolerated
general anesthesia surgery.
↓
The lower alveolar nerve function was detected before operation: light touch
detection,
acupuncture
detection,
hot
and
cold
stimulation,
two-point
discrimination detection.
↓
Surgical treatment
↓
Lower alveolar nerve function was detected 1 month after operation: light touch
detection,
acupuncture
detection,
hot
and
cold
stimulation,
two-point
discrimination detection.
↓
The main study measure: postoperative nerve injury rate was calculated until the
last subject was followed up.

5.2.3 Research schedule
5.3 Definition of study end
The end of the study was defined as the last subject to complete the last
follow-up or loss of follow-up or death.
5.4 Statistical Analysis
5.4.1 Sample size and calculation basis
Interview
Screening
period
Before
operation
Operation
Follow-up visit
V1
V2
V3
V4
V5
V6
V7
Follow-up time
1 day
before
enrollment
Enrollment
day
Day
after
V2
1 week
after
surgery
One
month
after
surgery
Three
months
after
surgery
1 y e a r
af t e r
s u rg e r y
Sign informed consent
Inclusion/exclusion
criteria
Demographic data
Medical history
Neural test score
Physical examination
Vital sign
Electrocardiogram
Blood routine
examination
Blood biochemistry
Liver function
Coagulation function
Imaging examination
Pathological
examination
Epidemiological
examination
Adverse event
evaluation

The main efficacy index of this study was the postoperative nerve injury rate of
endoscopic combined with intraoperative navigation-assisted treatment of giant
mandibular bone cysts. The hypothesis of this study is that the postoperative nerve
injury rate of endoscopy combined with intraoperative navigation-assisted treatment
of giant mandibular cyst is lower than that of traditional excision and curettage.
Research parameters were set as follows: α=0.025 (unilateral) and Power=80%.
According to the results of previous studies or pre-trials, the postoperative nerve
injury rate in the endoscopic navigation group was reduced by about 20% to 12%. 109
cases were calculated using PASS 15.0 software, and 122 subjects were included
considering the 10% shedding rate.
5.4.2 Data Analysis Set
Statistical analysis will be performed using SAS statistical analysis software
(V.9.4, SAS Institute). If there is no special explanation, unilateral test will be used for
the main index, and the control error α is 0.025; bilateral test will be used for the other
indicators, and the error α is =0.05. If you need to calculate confidence intervals,
calculate bilateral 95% confidence intervals unless otherwise specified.
(1) full analysis set (FAS) : comprised of all subjects who underwent surgical
treatment and were evaluated for efficacy. The data set is derived from all subjects by
eliminating subjects in a minimal and reasonable way.
(2) safety analysis set (SS) : A group of people who have received surgical treatment
and have safety evaluation data. In the safety analysis, all patients will be analyzed
according to the actual surgical group received.
(3) per-protocal set (PPS) : all subjects who met the protocol and did not use
concomitant drugs that affected the effectiveness evaluation, had good medication
compliance (between 80% and 120%), and excluded subjects who had a major
protocol violation and were judged to have a significant impact on the results. All trial
protocol deviations that result in subjects being excluded from the conformance
protocol set will be detailed in the Statistical Analysis Plan (SAP) and completed prior
to data locking.
5.4.3 Statistical Analysis Plan
Data description of statistical analysis, analysis methods of primary/secondary
indicators/safety
indicators,
statistical
correction
methods,
bias
control,
stratification/subgroup/sensitivity analysis, etc.
Demographic and other baseline characteristics: Based on FAS set, demographic
data, medical history, vital signs and other baseline data were statistically described.
The mean, standard deviation, minimum, maximum and median values were given for
measurement data (age, BMI, body weight, blood pressure, etc.). Counting data
(gender, tobacco and alcohol history, etc.) give the frequency and corresponding
percentage.
Analysis of efficacy index: The main evaluation index (postoperative nerve
injury rate) was estimated by point and the bilateral 95% confidence interval was
estimated by Clopper-Pearso exact probability method. If the lower limit of the 97.5%

confidence interval is lower than the postoperative nerve injury rate of the historical
control, it is considered that the efficacy of the navigational endoscopy group is better
than the historical control. Secondary efficacy indicators were analyzed using FAS
and
PPS analysis
sets.
For postoperative
recurrence indicators,
the median
postoperative recurrence time and bilateral 95% confidence interval were calculated.
For the rates of each index, point estimation was performed and the Clopper-Pearson
accurate probability method was used to estimate the bilateral 95% confidence
interval. For the continuity index, if it conforms to the normal distribution, its mean
and bilateral 95% confidence interval are calculated based on the normal distribution
method, otherwise based on hundreds.The quantile method calculates the median and
bilateral 95% confidence intervals.
Analysis of safety indicators: SS sets were used to make statistical descriptions
of the incidence of adverse events/serious adverse events, adverse reactions and other
safety indicators, and to list and describe the details of each adverse event for each
subject, including the type and severity of adverse events. Laboratory indicators, vital
signs, electrocardiogram and other safety-related indicators were compared and
evaluated before and after treatment, and clinical evaluation (normal, abnormal no
clinical significance, abnormal clinical significance, no investigation) was given
before and after treatment for statistical description.
The processing principle of missing/deleted/lost data: LOCF (last observation
carried forward) method was adopted to fill in the analysis of main indicators, that is,
the last observed data was used to fill in the data that failed to observe the main
indicators. Secondary indicators and security indicators are not filled.
VI. Research and intervention
6.1 Study intervention content
All enrolled patients underwent blood routine, liver function, heart function,
blood
biochemistry,
urine
routine,
stool
routine,
coagulation
function,
electrocardiogram, chest film, maxillofacial imaging and other related examinations
to ensure the safety of general anesthesia. Preoperative copies of the patient's
maxillofacial imaging data were digitally designed, professional software was used to
segment cystic lesions and segment the inferior alveolar nerve together, and then the
data was imported into the navigation system. After general anesthesia, gingival
trapezoidal incision or modified trapezoidal incision was made in the area of the cyst,
and the flap was turned to expose the bone surface. The bone window was opened
with electric grinding and drilling system, and the lesions were initially cureted with
curette immediately after the window opening. The occlusal surface and the internal
and external sides were mainly treated. The surgeon placed the mandibular reference
frame in the mandibular anterior tooth area, and used the navigation probe under the
guidance of navigation to accurately locate the anterior cavity of the capsule, the apex
of the root of the tooth and the ascending branch of the mandible. After accurate
positioning was obtained, the navigation adapter was loaded onto the endoscope to
locate the lesions in all directions and the inferior alveolar nerve under visual

conditions, and further precisely curettage the lesions in the cystic cavity with the
assistance of the adapter.
6.2 Preparation/handling/storage/Responsibilities
Any drug use or adverse reactions must be recorded in the patient's medical
record and recorded at the appropriate location in the CRF.
6.3 Study intervention compliance
The subjects were asked to return to the research center one month after surgery
for lower alveolar nerve function detection. The subjects were required to return to the
research center for maxillofacial imaging examination at 1 month, 3 months, 6 months,
1 year and 2 years after surgery to determine whether the cyst recurred and whether
there was new bone formation in the cystic cavity. During the same period of
follow-up, whether the oral wound healed in one stage, whether there was fluid
seepage or suppuration. The compliance of the study can be verified according to the
review status of the subjects. In the later follow-up, members of the research team
must conduct telephone follow-up communication with the subjects and reasonably
arrange the time of the subjects' review and visit.
6.4 Combination Therapy
Subjects with diseases requiring long-term drug control, such as hypertension,
diabetes, and coronary heart disease, should be evaluated by investigators and
relevant specialists to determine the impact of the disease and related research
protocols and determine the dosage and duration of adjuvant medication.
6.4.1 Rescue
The life risk of the subjects during the implementation of the clinical study
protocol should be implemented according to the clinical rescue protocol, such as
cardiopulmonary resuscitation, emergency airway management, and emergency
surgical treatment. The relevant records during hospitalization should be recorded in
the medical record system, and the occurrence after discharge should be recorded in
the adverse event record table. Meanwhile, researchers should analyze the cause of
rescue. As to whether it is related to the research and discussed, the discussion is
recorded in the rescue record simultaneously.
VII. Study intervention discontinuation or Subject discontinuation and
withdrawal
7.1 Study intervention discontinued
During the perioperative period of this study, if the number of patients with
serious complications such as anesthesia, serious postoperative infection or bleeding,
respiratory distress caused by severe edema of surrounding tissues, nerve lacerations
and other serious complications reached 30% of the participants, the study should be

suspended, and the safety of surgical methods of the study protocol should be
discussed to determine whether to adjust the study surgical protocol, and follow-up
should be conducted during the suspension of the study. Follow-up records of the
original subjects were maintained.
7.2 Subject discontinuation/withdrawal from study
When subjects suspend or withdraw from the study due to dissatisfaction with
the therapeutic effect of the study program or their own financial reasons, they should
communicate with them to encourage them to actively treat the treatment and help
them apply for public welfare funds to complete the treatment. In the perioperative
period, if serious complications of anesthesia, serious postoperative infection or
bleeding, respiratory distress caused by severe edema of surrounding tissues, nerve
tears and other serious complications reached 30% of the number of subjects, the
study should be suspended, and the safety of the surgical method of the study protocol
should be discussed to determine whether to adjust the study surgical protocol, and
follow-up should be conducted during the suspension of the study. Follow-up records
of the original subjects were maintained. In the case of clear withdrawal, the
investigator may continue to complete the follow-up without the study intervention.
7.3 Loss of access (measures to reduce loss of access and data loss due to loss of
access)
After the enrollment of subjects, the researchers should keep the contact
information of multiple subjects and the contact information of subjects' families.
After the subjects are discharged from hospital, the researchers should actively
contact the subjects by phone, timely understand the condition of the subjects, and
arrange the subjects to be admitted to the hospital for the next stage of treatment in
advance.
VIII. Adverse Events and unexpected events
An adverse event (AE) is an adverse medical event that occurs after a subject
receives treatment, but is not necessarily causally related to the treatment. An adverse
event may be any adverse and unexpected sign (including abnormal laboratory
findings), symptom, or disease associated with the use of the treatment, regardless of
whether it is related to the treatment. It includes, but is not limited to:
(1) exacerbation of disease that existed before the study treatment was used;
(2) Increased frequency or severity of paroxysmal events that existed before the study
treatment was used;
(3) abnormal changes detected or diagnosed after the study of treatment use, although
such abnormal changes may have existed before treatment;
(4) Exacerbation of disease or symptoms that were already persistent before the study
began.
Causal relationship between adverse events and treatment measures: In the trial,
researchers should conduct comprehensive analysis according to the specific

circumstances of adverse events and subjects' past history, concomitant diseases and
concomitant medication, etc., to determine the relationship between adverse events
and treatment measures. The relationship between adverse events and treatment
measures was classified as "definitely related, it may well be relevant, it may be
relevant, it may not be relevant and it may not be relevant."
(1) Unrelated: Adverse events were not associated with treatment.
(2) May not be relevant: the occurrence of an adverse event is more likely to be
related to other factors, such as co-medication or concomitant disease, or the timing of
the event indicates that it is unlikely to be causally related to the treatment.
(3) May be related: The occurrence of adverse events may be caused by therapeutic
measures. Cannot rule out whether other
Causes, such as: drug combination or concomitant disease. The occurrence of adverse
events and treatment measures have a reasonable time sequence, and the causal
relationship between the events and treatment measures cannot be ruled out.
(4) Likely related: The occurrence of adverse events may be caused by therapeutic
measures. The occurrence and treatment measures are
Reasonable chronological order.
(5) Definitely relevant: the type of adverse event has been identified as a result of the
treatment and cannot be otherwise justified
Explain, for example, drug combinations and concomitant diseases. The timing
of the event strongly suggests causality. The criteria for judging the severity of
adverse events can refer to the following criteria:
(1) Mild: mild symptoms or signs but tolerable.
(2) Moderate; Symptoms are significant enough to interfere with normal life.
(3) Severe: severe symptoms, has been unable to carry out normal activities.
All information about adverse events, whether referred to by the patient, discovered
by the investigator, or discovered by physical examination, laboratory examination,
etc., should be recorded in the study medical record and case report form. During the
trial, the occurrence time, duration, symptoms, signs and severity, measures taken and
outcome of adverse events should be carefully observed and recorded
And the relationship with treatment measures should be assessed, and appropriate
follow-up should be conducted. Possible adverse events include:
(5) Accidental risk of general anesthesia: After patients receive general anesthesia,
due to individual differences of patients, abnormal response to drugs may lead to
severe
suppression
of
respiratory
and
circulatory
functions
and
malignant
hyperthermia, etc., which can be life-threatening in severe cases. During anesthesia,
various adverse reflexes may induce cardio-cerebrovascular accidents or cardiac and
respiratory arrest, leading to death. In the event of anaesthesia related adverse
reactions, clinical treatment should be performed as a complication of normal surgery,
while the patient's medical record is detailed and the possibility of continuing the
clinical trial should be evaluated.
(6) Risk of tearing the inferior alveolar neurovascular bundle: When cystic lesions are
severely attached to the nerve, there is a risk of nerve tearing when separating the
mass, resulting in postoperative damage to the inferior alveolar nerve and numbness

of
the
lower
lip.
When
intraoperative
nerve
tears
occur,
intraoperative
neuroanastomosis should be performed to preserve nerve function as much as
possible.
(7) Risk of serious infection after surgery: When the scope of cystic lesions is too
large, the risk of postoperative infection increases, and the wound in the operative
area may not heal in one stage. In severe cases, it may spread to neighboring tissues,
resulting in infection of the maxillofacial space. In the case of severe infection,
anti-infection treatment should be actively applied. In the case of infection of
maxillofacial space or severe edema of surrounding tissue, the existence of indications
for incision and discharge of pus should be considered, and the vital signs of patients
should be closely monitored.
IX. Data collection and management
9.1 Case report form/electronic data record
Before the study began, the Redcap electronic database /EDC database was
established according to the contents of the paper case report form.
9.2 Data Management
The original data are uniformly recorded in the study medical records. According
to the contents of the study medical records, the researchers themselves or
designated/authorized trained personnel can complete the case report form and data
entry in the electronic database to ensure the integrity and accuracy of the information.
In order to ensure the accuracy of the data, the researchers conducted self-checks no
less than twice a year, regularly dispatched personnel to the sub-center to conduct
project quality control, and accepted the inspection of the hospital and school
management departments. If it is found that the data registered in the case report
form/electronic database is inconsistent with the original record (study medical
record), the researcher shall organize timely verification of the data, modify the
incorrect part as required, and make corresponding explanations if necessary.
X. Ethical requirements
This study complies with the provisions of the "Medical Device Clinical Trial
Quality Management Practice" and the "Administrative Measures for Conducting
investigator-initiated Clinical Studies in Medical and Health Institutions" (Trial) and
the Declaration of Helsinki. This study can only be carried out after the protocol is
approved by the Ethics Committee of our hospital before the trial starts. During the
study, if a protocol revision is necessary, the revised protocol must be re-submitted to
the Ethics Committee for review, and the researcher must wait until the Ethics
Committee agrees before implementing the new protocol.
Each enrolled patient must sign an informed consent form. A copy of the

informed consent form and contact information for the investigator and the ethics
committee must be provided to the patient upon request. This study will collect
clinical data and personal information of research subjects for scientific research,
which will involve the privacy rights of patients. Participants in this study and data
analysts signed confidentiality agreements, not to disclose patients' personal
information and disease-related information to any individuals and institutions
unrelated to this study. The collected patient data shall be managed in a unified
manner to prevent the leakage of personal privacy.
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