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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1281_Библиотеки_им_академика_М_И_Перельмана
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Thymectomy in Children
DOI: http://dx.doi.org/10.5772/intechopen.114888
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is important that complex or complicated cases should be evaluated with a multidisciplinary approach by a team consisting of pediatricians (pediatric neurologist,
pediatric infection specialist, pediatric oncologist, etc.), pediatric radiologist and a
surgeon experienced in both open and thoracoscopic thymectomy techniques. The
main diseases for which thymectomy should be considered are explained below in
detail.
. Congenital cardiac surgery
In the last decades, the number of operated congenital heart diseases is gradually
increasing in parallel to advances in diagnostic methods, surgery, and intensive care
facilities. In this context, today, complex and serious cardiovascular malformations
generally require open-heart surgery more frequently at an earlier in age. Partial
or complete removal of the thymus gland to improve surgical access is a common
procedure during corrective or palliative cardiac operations [10]. However, the
amount of eliminated tissue highly depends on the individual anatomy, surgeon’s
preference, type of surgery, and patient age. Thymectomy in young children implies
removal of the main source of T-cell differentiation, although other sources of
differentiation have been described [11]. Cavalcanti et al. suggested that early
thymectomy, either partial or complete, may be also associated with a reduction in
many T cell subpopulations and TCR diversity, and these alterations may persist
during long-term follow-up [12]. To overcome the negative immunological effects
of thymectomy, they proposed some alternative solutions, such as modifications of
surgical techniques with partial preservation of the thymus or autografting of gland
fragments [12, 13].
. Thymic hyperplasia
Thymic hyperplasia has several clinico-pathological manifestations. “Thymic
lymphoid hyperplasia” involves germinal center. It is rare in children and associated
with MG. In most pediatric cases, there is a reactionary/physiological growth of
the thymus gland, known as “true thymic hyperplasia”, in which the thymus gland
is histopathologically normal. “Rebound thymic hyperplasia” is a true hyperplasia
characterized by rapid and excessive growth of the thymus gland. This condition
can be seen after severe thermal burns or cardiac surgery, in tuberculosis, following
chemotherapy, or after stopping steroid treatment [1, 3]. “Non-lymphoid thymic
hyperplasia” cases are often asymptomatic and do not cause respiratory distress. The
majority of cases are seen in the first year of life, and the thymus gland returns to its
normal volume over time [3].
Thymic hyperplasia has been detected in 50–70% of patients with MG [14].
Hyperplasic thymus tissue can sometimes reach quite large sizes and put pressure on
the surrounding tissues. If necessary, a short-term steroid (prednisolone) treatment
may be administered to shrink the thymus. Such a therapy also allows thymic hyperplasia to be differentiated from non-lymphoid mediastinal masses. CT, MR imaging,
and mediastinoscopy can also be used for diagnosis [1]. Thymectomy should be
performed in symptomatic cases with rapid growth. Mediastinal radiotherapy is no
longer performed because it carries a high risk of thyroid carcinoma. In cases where
residual/recurrent lymphoma or a malignant tumor such as nodular thymic hyperplasia cannot be excluded, first PET and then, if necessary, exploration is recommended [3]. Nodular thymic hyperplasia is usually asymptomatic and is detected
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incidentally as a superior mediastinal mass on imaging methods. Complete blood
and bone marrow examinations are normal. During surgery, a lesion originating
from one lobe of the thymus and suppressing the adjacent normal tissue is observed.
In histopathological examination, T and B lymphocyte ratios are normal. Today,
thoracoscopic thymectomy is performed in most cases of thymic hyperplasia that do
not respond to conservative approach [2, 9].
. Myasthenia gravis (MG)
MG is an autoimmune disorder that affects the postsynaptic neuromuscular
junction and results in fatigue in voluntary muscles. Although the relationship
between the thymus gland and MG is not fully understood, the thymus is held responsible for the production of acetyl cholinesterase receptor (AChR) antibodies [15].
MG is frequently seen in women aged 20–30 and men over 60–70. Only, 10–30%
of immune MG is seen in children [3]. The clinical picture in children is classified in
three subgroups as “neonatal MG”, “congenital myasthenic syndrome”, and “juvenile MG”. Neonatal MG resolves spontaneously in the first few months. Congenital
myasthenic syndrome remains relatively stable throughout life and does not respond
to treatment methods (immunotherapy and thymectomy). Juvenile MG has similar
features to the adult disease. According to the Osserman-Genkins grading used to
determine the clinical picture of MG, findings may vary from mild ocular MG to
severe myasthenic crisis [16].
Measurements of AChR and muscle-specific tyrosine kinase (MuSK) antibodies
and edrophonium test give significant information for diagnosis and management.
AChR antibodies are present in approximately 80% of cases. MuSK antibodies are
detected in approximately 50% of the remaining patients. EMG and single fiber
EMG are highly predictive of diagnosis [17]. After the neurological diagnosis
is made, it should be investigated whether there is thymic pathology with CT
(Figure ) [1].
A possible association between the thymus and MG first suggested by chance
observation of improved symptoms in several myasthenic patients undergoing
thyroidectomy for goiters with concomitant resection of adjacent thymus gland in the
early 1900s [18]. After that, remarkable progress made in the understanding surgical
treatment of MG.
Figure 1.
Two cases of MG with thymic hyperplasia. Hyperplastic thymus (T) is seen in the thorax CT of a 14-year-old
patient (A). Thorax MR shows hyperplasic/hypertrophic left lobe in a 15-year-old patient with MG (from the
author’s own archive).
Thymectomy in Children
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Although there are no controlled studies with high-evidence level on surgical
treatment of MG, certain indications for thymectomy have been reported [17, 19].
These are listed below.
• Presence of thymoma.
• Early onset anti-AChR positive MG.
• Progressive widespread muscle weakness.
• Treatment-resistant non-thymomatous autoimmune MG.
It is important to carefully evaluate respiratory functions in these patients before
thymectomy. In the treatment of non-thymomatous MG, anticholinergics (pyridostigmine) and corticosteroids are used primarily. In selected cases, immunoglobulins, immunosuppressors, and plasmapheresis may be useful [17]. In (highly) active
generalized MG, complement inhibitors (currently eculizumab and ravulizumab)
or neonatal Fc receptor modulators (currently efgartigimod) are recommended for
AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase
(MuSK)-Ab-positive status [20]. In cases of failure and in the presence of generalized
symptoms, thymectomy has begun to be applied to children as an effective method
[16, 21]. However, there is no consensus in the literature regarding the timing of
thymectomy, which is a procedure that can be performed safely in children [22]. The
general approach is to perform thymectomy in cases where there is no response to
pharmacotherapy within 1 or 2year [23]. The thoracoscopic approach for thymectomy has attracted attention in recent years. The goal is to remove all thymic tissue.
It has been stated that even an amount of 3g of residual thymus tissue can cause MG
symptoms [24]. In their series including 12 cases, Ashfaq et al. stated that thoracoscopic thymectomy is an effective option to control the disease with low morbidity
and short hospitalization time [16]. Goldstein et al. obtained similar findings in terms
of effectiveness in their study comparing cases in which thoracoscopy, sternotomy,
and thymectomy were performed [21].
. Thymic cysts
While these cysts can be located within the mediastinal thymus tissue, they
can also be seen anywhere from the neck to the diaphragm in anterior or posterior
mediastinum where ectopic thymic tissue may be present. Most cases are diagnosed
after pathological examination. Histopathologically, cysts are lined with ciliated
columnar (respiratory) epithelium and characteristically contain Hassall corpuscles.
They may contain lymphocyte infiltration and normal thymic tissue, and both
inflammatory and granulomatous changes may be seen [9]. Their location in the
neck region is lateral to the midline and may vary from the submandibular area to
the suprasternal fossa along the sternocleidomastoid muscle line [25]. The cysts can
be congenital or acquired. Congenital ones are usually located on the left side and
originate from the thymopharyngeal duct. They can be unilocular or multilocular
[26]. Acquired ones may coexist with inflammatory or neoplastic diseases (thymoma, germ cell tumors) [3].
Thymic cysts are usually asymptomatic. However, the cysts become symptomatic
when microorganisms reach the cyst through remnants of the thymopharyngeal
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duct (i.e., when they infected), bleeding occurs into the cyst, and the cyst grows and
causes pressure on surrounding tissues and organs. Those with large dimensions in
the neck may also cause cosmetic problems.
Findings on chest radiography are mostly non-diagnostic. On CT or MRI, a wellcircumscribed, fluid-dense mass is detected in the original or ectopic location of the
thymus [1]. Cyst excision is recommended in ectopic locations, and thymectomy is
recommended in original locations [2, 8].
. Ectopic thymic tissues
Since ectopic thymic tissues are usually asymptomatic, the majority of cases
are detected incidentally during ultrasonography, which is frequently used for the
differential diagnosis of patients presenting with neck-related symptoms [27]. Most
ectopic tissues are located in the thyroid gland. Ultrasound has a high predictivity
for diagnosing ectopic thymus, providing a unique appearance and allowing specific
diagnosis [28]. In childhood, ectopic intrathyroidal thymus tissues generally remain
stable, but sometimes their size may decrease or grow. Stable ectopic tissues can be
safely followed without the need for excision and physicians should reassure parents
about its benign course. However, microcalcified intrathyroidal nodules that grow
during follow-up, which may mimic thyroid cancer, ultimately require invasive
diagnostic procedures or surgery [4].
. Thymolipoma
Thymolipoma is a slowly progressing benign tumor that is more common in young
adults and rare in children. It is considered a hamartomatous lesion consisting of a
mixture of thymic and mature fatty tissues. Although approximately half of the cases
are asymptomatic, the tumor can reach very large sizes over time [3]. CT and MRI
show a tumor structure mostly consisting of fatty tissue, but the tumor also contains
different soft tissue components scattered throughout [1]. Excision is both a diagnostic and therapeutic method in patients who have a progressive course and cause mass
effect on neighboring structures [9].
. Thymoma
Thymomas are mediastinal masses that are rarely seen in children. They are
mostly seen in the third and fourth decades of life. Only 2% of all thymomas are
diagnosed in childhood, and these account for less than 1% of all mediastinal tumors
[3]. Thymomas originate from the thymic epithelium and can vary markedly in both
size and appearance. Histopathologically, they are low-grade malignant tumors. In
30–40% of cases, there is a tendency to invade the surrounding tissues (pericardium,
pleura, lung, and large vessels) [29, 30]. This type of tumor tissue that spreads beyond
the capsule is called invasive thymoma. Lymphatic and hematogenous metastases are
rare, but transdiaphragmatic spread may occur. The recent WHO classification of
thymic epithelial tumors including thymomas, thymic carcinomas, and neuroendocrine tumors is summarized in
Table [31]. Thymic carcinomas and neuroendocrine
tumors are exceedingly rare and constitute 1% of all thymic tumors.
According to adult data, 30–50% of patients with thymoma have MG, while
thymoma is detected in 10–25% of patients with MG [29]. Advanced imaging methods such as CT, MR, and PET-CT are used for diagnosis and surgical planning [1].
Thymectomy in Children
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Behavior Code Histological Description
*
3
3 Squamous carcinomas
3 Adenocarcinomas
3 Adenosquamous carcinomas
3 Salivary gland-like carcinomas
3 Undifferentiated carcinomas
3 Thymic carcinomas
3 Thymic neuroendocrine neoplasms
3 Neuroendocrine tumors
3 Neuroendocrine carcinomas
*Behavior code : malignant tumor, primary site.
**Except for lipofibroadenoma and micronodular thymoma with lymphoid stroma.
Table 1.
Main thymic epithelial tumors according to the 2021 WHO classification [31].
Thymomas
**
A staging system (Masaoka) has also been developed to determine the treatment
method and prognosis of thymomas. There may be progression from stage I, without capsule invasion, to stage IV, with distant metastases [14]. A multidisciplinary
approach should be applied at diagnosis and during therapy [32].
Thymectomy with no adjuvant approach is the best treatment option in early
stages, which accounts for 85–90% of cases are at the time of diagnosis. Recently, it
has been suggested that robotic thymectomy has better cosmetic results and morbidity in early noninvasive thymoma [33]. Since incomplete tumor resection is associated
with a high-recurrence rate and poor outcome, it should be avoided. While anterior
region lymph node dissection is recommended for non-invasive thymomas, an
additional systemic sampling of deep lymph nodes should be performed for invasive
thymomas. Neo-adjuvant chemotherapy is recommended for advanced tumors
but the prognosis is still poor [9, 30]. Radiotherapy is also applied as a palliative or
adjuvant therapy because of the radiosensitive nature of the tumors. In the EXPeRT
study, which included one of the largest series of children, it was reported that two of
16 thymoma cases and 15 of 20 thymic carcinoma cases were mortal, and the 5-year
survival rate in thymic carcinoma was 21% [29]. Additionally, a need for multicenter,
multidisciplinary studies in collaboration with adult thoracic surgeons.
. Other tumors of the thymus
Thymic carcinoids are very rare and develop from normally existing neuroendocrine
cells in the thymus gland. Approximately half of the tumors are functionally active and
may present with Cushing’s syndrome. Less than 5% of primary thymic carcinoids are
seen in children. They may show aggressive behavior with tendency to metastasis and
local recurrences after thymectomy [1, 3].
Germ cell tumors, including mature or immature teratomas located in the anterior
mediastinum, lymphoma, and leukemic infiltrates are topographically related to the
thymus and should be considered in the differential diagnosis. Although lymphoma is
the most common anterior mediastinal mass in children, isolated thymic involvement
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is extremely rare. Thymic involvement associated with advanced stage of Hodgkin or
non-Hodgkin lymphoma is more likely [1, 14].
. Preoperative evaluation and preparation
The preoperative evaluation should include safe surgery guidelines and standard
institutional protocols, comprising a comprehensive history and physical examination. The extent of work-up depends on the disease necessitating a thymectomy and
should be individualized. Radiological identification of adjacent structures and blood
vessels (especially, innominate vein) during preoperative evaluation has utmost
importance to avoid from intraoperative complications [14, 34].
Specific anesthesiologic measures in patients with an anterior mediastinal mass
should be strictly followed to avoid airway compressing during induction phase.
For anesthetic management, placement of a double-lumen endotracheal tube for
sequential lung isolation in older children and adolescents, or a standard single
lumen endotracheal tube in young children can be used. Single lung ventilation with
selective bronchial intubation or with a blocker can be also preferred in selected
patients [35].
Medical history should include any past-history of coagulation disorders, allergic
conditions, medications used, radiation to the neck or chest, and prior surgery in
the neck, mediastinum, or thorax. The patient should be examined systematically to
detect any neurological deficits, cervical/supraclavicular lymphadenopathy, cervical/
thoracal spine anomalies, and chest wall deformities, including sternum.
Preoperative work-up consists of routine baseline tests (complete blood count,
chemistry, and coagulation studies), ECG, and other studies, as indicated. Further
laboratory studies, such as thyroid function tests, tumor markers (alpha fetoprotein
and beta-hCG), or myasthenia gravis antibodies (anti-AChR, anti-MuSK), can also be
obtained if necessary. Pulmonary function tests help stratifying risk for pulmonary
complications and serve as a baseline for postoperative comparison in patients with
a coexisting lung disease. Simple or sophisticated radiological imaging methods such
as chest x-ray, ultrasound, CT, MRI, and PET-CT are helpful to establish diagnosis or
differential diagnosis [35].
First-generation cephalosporins are used for prophylaxis unless there is a known
immunological disorder or susceptibility to infection. Aminoglycosides are contraindicated in patients with MG because they increase neuromuscular blockade.
. Thymectomy techniques
Although the term thymectomy simply defines the surgical removal/excision of the
thymus gland, detailed literature review reveals that there are different definitions and
practices in terms of access routes used and the extend/limits of the excision [34, 36].
In this context, there are three basic access methods for thymectomy (Tabl e ): (I)
transsternal, (II) transcervical, (III) thoracoscopic (VATS). Each of these can be used
individually or in different combinations. On the other hand, when the prevalence and
limits of the excision procedures are considered, defining thymectomy becomes more
complicated. It may be informative to summarize these procedures in three groups [3]:
(I) Simple/Standard thymectomy, (II) Extended thymectomy, (III) Radical/Maximal
thymectomy.
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Surgical techniques for thymic disorders
Thymectomy Techniques Transcervical Thymectomy
Simple
Extended
Thoracoscopic Thymectomy
Conventional
Video Assisted Extended Thymectomy
Transsternal Thymectomy
Simple
Extended
Combined (Transcervical+Transsternal) Thymectomy
(Radical Thymectomy)
Surgical Techniques Other Than
Thymectomy
Excision of Ectopic Thymic Cyst
Transcervical (for cervical ectopic cysts)
Transsternal/Thoracoscopic (for mediastinal ectopic cyts)
Excision of Ectopic Thymic Tissue
Thyroidectomy/Thyroid Lobectomy (for intrathyroidal location)
Transcervical/Transsternal/Thoracoscopic (for extrathyroidal location)
Table 2.
Classification of surgical techniques for the treatment of thymic disorders (modified from Crabbe and Parikh [3]).
Simple thymectomy involves complete removal of both lobes of the gland using
a single access method. In both extended transcervical thymectomy and extended
transsternal thymectomy, excision margins progress toward potential locations where
ectopic tissues outside both lobes may be found. Radical thymectomy is performed
with the combined use of cervical incision and sternotomy. It describes the removal
of all thymic tissues along with the pericardial fat pad in the region from the inferior
thyroid gland to the diaphragm, including areas where ectopic thymic tissues may be
present. The dissection is extended laterally toward the phrenic nerves and utmost
care is taken to preserve it.
Besides the commonly used techniques of thymectomy, some rare surgical procedures have also been reported to treat thymic diseases. Pure mediastinoscopic thymectomy, subxiphoid thymectomy, and partial thymectomy can be mentioned among
these ones, but will not be discussed here [37].
. Transsternal approach
Median sternotomy provides excellent visibility for thymectomy (Figures and ).
It is an approach especially suitable for large thymus and thymomas. Although there
is a risk of complications related to the sternal bone, pleural injury is rarely encountered. It has also been reported that a simple thymectomy can be performed with
a partial sternotomy that includes only the manubrium. Care should be taken to
protectthe phrenic and recurrent nerves on both sides, as well as the main vascular
structures [3].
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Figure 2.
Transsternal approach to a case of thymoma associated with MG. Appearance of anterior surface of the
thymus after median sternotomy (A), and dissection of posterior surface of the gland from pericardium and
left innominate vein in another case (B) (from the author’s own archive; *left innominate vein anterior to the
thymus).
Figure 3.
Transsternal approach to a case of thymoma associated with MG. Appearance of anterior mediastinum after
extended thymectomy (A) and thymectomy material (B) (from the author’s own archive, *right innominate vein,
**left innominate vein).
• The skin incision should be cosmetically located in the exact midline. The length
of the incision is about half or two third of the length of the sternum.
• Before sternotomy, skin flaps are mobilized circumferentially. The mobility of
the skin flaps allows easy access to the suprasternal notch and the manubrium
with the appropriate retraction.
• The sternum is generally divided from top to bottom using a pneumatic or
electrical sternal saw. Once the sternum is split, periosteal bleeding points from
two edges are controlled with cautery, and bone wax is applied to seal the bone
marrow.
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• Then the sternal retractor is inserted, gradually opened, and sterno-pericardial
ligaments are separated.
• The thymic dissection is begun by caudal and lateral aspects of the gland following visible plans between pericardium and thymus. The dissection is carried out
cephalad along the pericardium toward the brachiocephalic vein. It encompasses
mediastinal fat from the retrosternal space to the phrenic nerve. If there is
pleural or pulmonary involvement, the mass is resected en bloc.
• The horizontal extent of dissection is widened from one phrenic nerve to other
phrenic nerve. Exploration of aorto-pulmonary window is a critical step of
procedure, especially in patients with thymoma.
• Care should be taken to avoid mechanical or electrocautery injury to the phrenic
nerve.
• The thymic vein(s) are usually found at the lower border of the brachiocephalic
vein, near the midline, and are cut after clip or suture ligation.
• Arterial blood supply from the internal thoracic artery or inferior thyroid artery
may be encountered and these branches should be ligated/clipped and divided.
• Than the gland totally excised with or without surrounding mediastinal
fattissue[6].
• Before sternal closure, a drain is placed in the anterior mediastinum.
• If pleural space is entered as part of the en bloc resection, a separate chest tube is
inserted.
• The sternum is closed using sternal wires.
• If necessary, a superficial drain can be placed under skin flaps before closing skin
with subcuticular stitches.
Indications: All thymic masses predicted to be resectable, regardless of their sizes
and invasiveness (thymic hyperplasia, MG, thymoma, etc.).
Contraindications: Sternal anomalies and acute or chronic infections of breastbone. Inability to tolerate general anesthesia, hemodynamic instability, severe
coagulopathy. Repeated sternotomies also pose a relative contraindication.
Advantages: Median sternotomy provides excellent visibility for thymectomy,
allowing safe resection of huge thymic mases and invasive thymomas.
Disadvantages: Large scar tissue, more postoperative pain, prolonged drainage,
and long hospital stay.
. Transcervical approach
Although transcervical approach has a nice cosmetic appearance, rapid healing
and is a good way to reach the upper-anterior mediastinum, it requires a high level
of technical experience. It is more suitable for cases that are relatively small and do
not show inferior growth/location [3]. When performing colon interposition for
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esophageal replacement, this approach can be used to make a space for the colon segment at the thoracic outlet and to eliminate external compression/obstruction during
and after the cervical anastomosis [38]. We used this technique in three patients who
underwent esophageal replacement due to isolated esophageal atresia (n=2) and
caustic esophageal stricture (n=1).
• Appropriate position (hyperextension), field illumination (headlamp), and the
presence of automatic retractors increase the success of the technique.
• A transverse, curved incision along the Langer lines is made just above the
suprasternal notch. To reach the back of the manubrium, subplastimal plane
is entered, upper and lower skin flaps are prepared, and the strep muscles are
divided in the midline. If necessary, the sternal heads of both sternocleiodomastoid muscles can be partially transsected to provide a better exposure.
• Then, the upper border of thymus is identified, and the gland is dissected from
top to bottom, close to thymus capsule.
• Special devices to provide better mediastinal exposure such as Cooper and Parker
retractors
• Surrounding tissues, nerves, and vascularities are carefully separated from
the gland. The dissection is deepened by gently pulling the gland upward.
Thymectomy is completed after the thymic vessels are tied and divided.
• The incision is closed with subcuticular sutures, with or without a drain being
placed in the wound.
Indications: Normal thymus or mild/moderate thymic hyperplasia by CT scan,
early or small thymomas in which the masses are completely contain within the
thymus, selected cases of retrosternal esophageal replacement to provide adequate
mediastinal space.
Contraindications: Giant thymus or thymic hyperplasia and large/invasive
thymomas. Inability to tolerate general anesthesia, hemodynamic instability, and
severe coagulopathy. Relative contraindications are previous median sternotomy,
thyroidectomy, and cervical spine surgery/trauma which may create added risk for
extreme hyperextension of the neck.
Advantages: Better cosmetic appearance (less scar) than transsternal approach,
no cutting of the sternum, minimal local pain without intercostal neuralgia, and
rapid and better wound healing.
Disadvantages: Limited exposure of anterior mediastinum, difficulty to secure
the surgical field even if the surgeon is familiar with the procedure, and necessity of
a high level of technical experience. This technique is challenging when performed
for removal of large tumors or for combined resection of adjacent organs. A relative
disadvantage is that some patients do not like such an incision, which cannot be hidden by clothing.
. Endoscopic approaches
Endoscopic or minimal invasive thymectomy can be carried out via the traditional
thoracoscopic approach or, more recently, the robotic approach.
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