A Comparative Study of Preoperative and Intraoperative Carbon Nanoparticles Injection in Patients Undergoing Thyroid Cancer Surgery
Phase: PHASE3
Conditions: Papillary Thyroid Cancer
Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University

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A comparative study of
preoperative and intraoperative
carbon nanoparticles injection in
patients undergoing thyroid
cancer surgery
Research program
NCT ID：Not yet assigned
Date of document：2025.01.11

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Research program
Ⅰ.Background of the study
1. Thyroid Cancer and Thyroid Surgery
Thyroid cancer is a common malignant tumor in the neck, and its incidence
accounts for about 1% of the total incidence of malignant tumors, and its incidence
rate ranks fifth in the incidence of tumors. In recent years, with the improvement of
residents' health awareness and the wide implementation of neck examination, the
detection rate of thyroid cancer has been increasing rapidly, and the patient group is
found to have a tendency to be younger, while female patients are predominant and
significantly higher than male patients.
Except for undifferentiated cancer, surgery is still one of the most important
treatments for all types of thyroid cancer, which is supplemented by radionuclide,
TSH inhibition, and external radiation, etc. Surgery can effectively improve the
prognosis of the disease by completely removing the lesions. Surgical treatment of the
thyroid gland is mainly divided into two parts: thyroidectomy and cervical lymph
node dissection. The extent of thyroidectomy is still divided, but there is a consensus
that the lobes should be the minimum extent of resection. In recent years, total
resection and subtotal resection have also been gradually accepted.
There is a basic consensus that the minimum scope of lymph node dissection is
central lymph node (VI) dissection, because the main metastatic route of thyroid
cancer is lymphatic metastasis, and it may appear earlier, for example, the lymphatic
metastasis rate of initially treated patients with papillary thyroid cancer can be as high
as 20% to 90%. For patients with positive lymph nodes or highly suspected in
auxiliary examination, modified radical translymph node dissection is needed, i.e., on
the basis of thyroidectomy, translymph node dissection in zone II-VI is performed
while
preserving
sternocleidomastoid
muscle,
internal
jugular
vein
and
parasympathetic nerves. It is currently believed that under the premise of surgical
safety, the number of central lymph node dissection can effectively reduce the risk of
postoperative recurrence, and at the same time can be combined with the pathology to
provide patients with precise treatment and clarify the stage of cancer.

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In the past, open neck surgery was used in clinical practice, which would leave
scarring on the neck and affect the appearance, and at the same time, patients could
lose part of the function of the anterior cervical skin, and a few patients had a foreign
body sensation and skin linkage during swallowing activities, which had an impact on
the patients' satisfaction with the surgery. Thus, in recent years, with the development
of minimally invasive medical technology, the luminal thyroid surgery has come into
people's view. Currently, the more commonly performed laparoscopic surgeries can be
categorized into axillary approach, oral vestibular approach, thoracic breast approach,
etc., and there are also case reports of multi-approach combined surgeries. These new
laparoscopic surgical treatments have been widely used in the clinic. While meeting
the requirements of tumor resection as much as possible, laparoscopic surgery is
gradually accepted by patients because of its smaller incision and stronger protection
of the function and integrity of the neck skin.
2. Postoperative complications of thyroid cancer
Hypoparathyroidism and laryngeal recurrent nerve injury are the most common
complications of radical thyroid cancer surgery, whether it is open surgery or luminal
approach, and once these complications occur, they will have a serious impact on the
patient's quality of life in the postoperative period.
(1). Hypoparathyroidism
A domestic study on the occurrence of hypoparathyroidism after radical thyroid
cancer surgery in patients with differentiated thyroid cancer showed that the incidence
of hypoparathyroidism after radical thyroid cancer surgery ranged from 0.5% to
65.0%. In clinical practice, hypoparathyroidism is usually categorized as temporary
and permanent. Temporary hypoparathyroidism is mainly characterized by transient
hypocalcemic
symptoms
such
as
numbness
of
hands
and
feet;
permanent
hypoparathyroidism is characterized by long-term hypocalcemic symptoms such as
numbness of hands and feet and twitching of limbs, and in severe cases, it may also
lead to convulsions and laryngeal spasms, which can seriously affect the patient's
health
and
even
cause
death.
Transient
hypoparathyroidism
with
transient
hypocalcemia is usually considered to be caused by destruction of the parathyroid
blood supply (the blood supply of parathyroid glands mainly comes from the thyroid

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artery, and ligation of the thyroid blood supply artery during bilateral thyroidectomy
during surgery can have an effect on the blood supply to the parathyroid glands,
which can become dysfunctional due to obstruction of venous return and stagnation of
the parathyroid glands); whereas, permanent hypoparathyroidism is mostly related to
the
destruction
of
the
blood
supply
to
the
parathyroid
glands.
Permanent
hypoparathyroidism is mostly associated with disruption of the parathyroid blood
supply leading to ischemic necrosis or misdirected parathyroidectomy.
Previous studies have suggested that the incidence of postoperative temporary
hypoparathyroidism ranges from 7% to 38%, with most patients returning to normal
within 6 months as serum parathyroid hormone levels rise. In contrast, the incidence
of permanent hypoparathyroidism ranges from 1% to 7% of patients who do not have
complete resolution of symptoms at 6 months after surgery and who also require oral
calcium to maintain normal calcium levels. There is no doubt that hypothyroidism can
have a serious impact on the quality of life and health of patients and greatly reduces
their satisfaction with surgery.
(2). Injury to the recurrent laryngeal nerve
Injury to the recurrent laryngeal nerve usually occurs during dissection of the
thyroid artery, ligation, or freeing of the trachea after severing the thyroid isthmus.
Patients with unilateral recurrent laryngeal nerve injury will suffer from hoarseness,
mild respiratory and swallowing difficulties, and choking on drinking water; patients
with bilateral recurrent laryngeal nerve injury will suffer from respiratory difficulties,
respiratory failure, and even asphyxia in severe cases. At this stage, it is usually
advocated to expose the laryngeal recurrent nerve in the process of freeing the trachea,
which can reduce the incidence of laryngeal recurrent nerve injury to a certain extent.
3. carbon nanoparticles and carbon nanoparticles negative
contrast technology
Carbon nanoparticles is an effective and harmless negative developer, and there
have been many studies confirming that carbon nanoparticles can be used to identify
parathyroid glands in thyroid surgery. Nanocarbon suspensions consist of nanocarbon
particles with an average diameter of 150 nm. The cellular gap between capillary

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endothelial cells ranges from 20 to 50 nm, and the gap between capillary lymphatic
endothelial cells ranges from 120 to 500 nm, with an underdeveloped basement
membrane. Therefore, carbon nanoparticles cannot enter the blood vessels when
injected into the thyroid tissue; it rapidly enters the lymphatic vessels or lymphatic
capillaries through phagocytosis by macrophages and is retained in the lymph nodes.
In
thyroid
surgery,
by
injecting
nano-charcoal
into
the
thyroid
gland,
the
nano-charcoal can diffuse through the gland and the lymphatic system, thus staining
the thyroid tissue and lymph nodes black, while the tissues not subject to the
lymphatic return of the thyroid gland will not be stained, such as parathyroid glands,
the trachea and the supraglottic laryngeal reentrant nerve, which can keep their
original color, different from the thyroid tissue and lymph nodes, thus playing an
effective role in the protection. Protecting effect.
As
a
third-generation
tracer, carbon
nanoparticles
suspension
is
highly
conductive to the lymphatic system, especially in the display of small lymph nodes
(<2mm), and the staining is fast-acting, long-lasting, effective in identifying
parathyroid glands, and mildly toxic. The importance of charcoal carbon nanoparticles
in parathyroid protection has been noted by many thyroid surgeons and many clinical
trials have been conducted. It has been demonstrated that intraoperative injection of
carbon nanoparticles can effectively increase the quality of intraoperative parathyroid
gland detection and lymph node dissection, and reduce postoperative hypocalcemia
and other adverse reactions, and at the same time, the carbon nanoparticles suspension
injections in this trial have a high degree of safety, and no patients had allergic
reactions to the injections.
However, there is no complete clinical guideline for preoperative intraglandular
injection of carbon nanoparticles, and there is no standardized dosage for the
appropriate injection time, injection dose, and injection method. Meanwhile, there is
still the problem of carbon nanoparticles leakage during the procedure, which may
affect the recognition and protection of the parathyroid glands by accidentally
coloring the thyroid region black.
It is well known that the use of charcoal CNS is usually performed during
surgery, but in our medical center, we found that preoperative injection of carbon
nanoparticles by fine needle aspiration under ultrasound guidance can have better
results by reducing CNS leakage in the surgical area. Possible reasons for this include:
(i)
preoperative
ultrasound-guided
intra-glandular
lobe
injection
of
carbon

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nanoparticles does not have to open the surgical peritoneum of the thyroid gland,
which reduces possible lymphatic vessel damage and makes lymphatic drainage more
consistent with normal physiology; (ii) preoperative injection allows for a more
adequate time for lymphatic dispersion of the carbon nanoparticles; and (iii)
preoperative labeling of suspected metastatic lymph nodes by carbon nanoparticles
injection further improves the tracing effect of the lymph nodes.
Ⅱ.Purpose of the study
The purpose of this study was to investigate the effect of carbon nanoparticles
injections at different preoperative and intraoperative times on surgical procedures
and postoperative complications in patients with unilateral and bilateral papillary
thyroid cancer or lymph node metastases.
Ⅲ.Study population
One hundred and fifty patients who came to our hospital from January 2025 to
June 2025, who were diagnosed with unilateral bilateral PTC or lateral LN metastasis
by preoperative FNA (fine needle aspiration) or preoperative ultrasonography
suggestive of TRAIDs grading 4a and above, and who were proposed to undergo
laparoscopic thyroid surgery, were selected. Based on the objective conditions and
subjective requirements of the patients, these patients were first divided into a partial
thyroidectomy group (i.e., a unilateral lobectomy or partial thyroidectomy was
performed) and a total thyroidectomy group (a total thyroidectomy was performed),
and under the two groups, according to the timing of carbon nanoparticles injections,
they were divided into two subgroups: a preoperative subgroup and a suboperative
subgroup. In the preoperative subgroup, carbon nanoparticles was injected into the
thyroid gland 2-6 hours prior to surgery, whereas in the suboperative subgroup,
carbon nanoparticles was injected intraoperatively.
Inclusion Criteria:
(1).Preoperative pathological assessment indicated the presence of thyroid cancer

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with a maximum diameter of less than 4 cm.
(2).Postoperative pathological evaluation confirmed bilateral thyroid cancer or
lateral lymph node metastasis.
(3). Vocal cord examination conducted one week prior to surgery revealed no
abnormalities.
(4). The patient had no history of prior thyroid surgery and required a total
thyroidectomy.
(5). Blood pressure was stably controlled.
(6). The patient regained consciousness and was able to communicate normally.
Exclusion criteria
(1) Prior to enrollment, the patient had received radiotherapy, chemotherapy, or
isotope therapy;
(2) A documented history of thyroid surgery;
(3) Age under 16 years;
(4) Known allergies to the medications under investigation or an inability to
tolerate surgical intervention;
(5) Presence of a retrosternal thyroid tumor;
(6) Tumor invasion of the parathyroid glands and/or the recurrent laryngeal nerve
during surgical procedures;
(7)
Postoperative
pathology
suggestive
of
medullary
carcinoma
or
undifferentiated carcinoma;
(8) Development of a postoperative tracheal fistula.
Ⅳ.Observation indicators
(1). General information: age; gender; height; weight; BMI; tumor size; tumor
location; pathology results; preoperative serum calcium; preoperative thyroid
hormone;
(2). Preoperative parathyroid hormone levels; preoperative TSH; preoperative
vocal cord movement problems.
(3). Carbon nanoparticles injections: carbon nanoparticles injection site; number
of carbon nanoparticles injection needles; carbon nanoparticles injection dose.

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(4). Carbon nanoparticles staining: thyroid staining; lymph node staining;
parathyroid staining; nanocarbon leakage.
(5). Intraoperative data: length of surgery, number of lymph nodes cleared,
amount of intraoperative bleeding.
(6). Postoperative data: postoperative pain duration; postoperative drainage;
postoperative
hospitalization;
postoperative
serum
parathyroid
hormone;
postoperative
laryngeal
recurrent
nerve
stimulation
and
injury;
postoperative
hematoma; postoperative tracheal fistula.