Abstract

OBJECTIVES

Experience in video-assisted thoracoscopic (VATS) thymectomy is limited in paediatric patients with non-thymomatous myasthenia gravis (MG). The aim of this study is to evaluate the medical status and surgical results of paediatric patients who underwent a VATS thymectomy.

METHODS

Of the 367 VATS thymectomies performed for MG patients in our Department of Thoracic Surgery between June 2002 and April 2013, 40 patients were in the paediatric age group. The data were evaluated retrospectively. Age, sex, duration of disease, body mass index, prescribed medication, duration of the operation, complications, chest tube duration, length of postoperative hospital stay and pain score using a visual analogue scale were analysed.

RESULTS

The average age was 14.8 ± 2.2 years (range, 8–18 years), and 27 (68%) patients were female. The electromyography and acetylcholine receptor antibody tests were positive in 30 (75%) and 27 (67%) patients, respectively. The mean quantitative MG score was 11.5 ± 5.3. The mean prescribed preoperative pyridostigmine bromide dosage was 209 ± 112 mg. Eleven (27.5%) patients were on corticosteroid treatment and 22 (55%) received intravenous immunoglobulin treatment preoperatively. There were no open conversions or mortalities. The average duration of the operation was 48.9 ± 31.3 min. All patients were extubated on the table and only one (2.5%) required mechanic ventilation for 18 h postoperatively. Three (7.5%) patients experienced complications. The average duration of chest drainage and postoperative stay were 20.5 ± 12.1 h and 1.8 ± 1.0 days, respectively. The average pain score using a visual analogue scale was 2.3 ± 1.2.

CONCLUSIONS

A right-sided VATS thymectomy is a safe procedure in paediatric patients with MG.

INTRODUCTION

Myasthenia gravis (MG) is an autoimmune disease caused by specific antibodies inducing a neuromuscular transmission defect that results in fluctuating muscle fatigability. Clinical and surgical studies of MG and thymectomy have primarily been performed in the adult population. Paediatric MG is rare; therefore, it was difficult to conduct a prospective, randomized, controlled study to evaluate treatment outcomes and efficacy. Recently, a retrospective study demonstrated that the effectiveness of thymectomy in a paediatric generalized MG population was similar to that in the adult population [1]. Combined modalities for the treatment of the disease are systemic use of cholinesterase inhibitors (e.g. pyridostigmine bromide), corticosteroids or immunosuppressive agents; thymectomy; intensive care unit monitoring; intravenous immunoglobulins (IVIG) or plasmapheresis for patients with myasthenic crisis.

Video-assisted thoracoscopic surgery (VATS) resection of the thymus was first reported in the late 1990s [2–5]. Published recently, the largest experience in the literature to date was of 12 VATS and 16 open approaches [6]. However, there are only limited reports of VATS thymectomy in the paediatric population [7–10]. The appropriateness of a VATS thymectomy in paediatric patients is still being debated. For most paediatric MG patients, a thymectomy is performed using median sternotomy techniques with either partial or total sternotomy. Here, we report on our experience with right-sided VATS thymectomy in paediatric MG patients. The aim of this study is to evaluate the medical status and surgical results of this experience.

PATIENTS AND METHODS

Patient characteristics

Paediatric MG patients younger than 18 years who were referred to the Department of Thoracic Surgery at Istanbul Medical School between June 2002 and April 2013, and their parents were informed about thymectomy by sternotomy, which is the standard surgical approach, and thymectomy by videothoracoscopy as an alternative approach. Informed consent was obtained from the families of all of the patients, and this study was approved by our institutional review board. The patients who chose to be treated with videothoracoscopic surgery underwent VATS and the data were evaluated retrospectively. The data of 40 paediatric VATS thymectomy patients were extracted from a total of 367 VATS thymectomy and thymothymectomy operations. During the same period, two open thymothymectomy operations were performed in children for recurrences, operated on elsewhere 2 and 8 years ago. Age, sex, duration of disease, body mass index, prescribed medication, quantitative MG score (QMG), modified Osserman–Jenkins score, length of the operation, complications, chest tube duration, duration of hospital stay, pain score [visual analogue scale (VAS)] and histopathological findings were recorded, and a retrospective analysis was performed. Because the data were collected prospectively from 2002, Myasthenia Gravis Foundation of America data were available for patients only after 2007. Pathology reports were evaluated to report histological data accurately.

Indications

Paediatric patients with generalized MG were recommended for thymectomy by the Departments of Neurology and Paediatric Neurology at Istanbul Medical School, Istanbul University. Patients who were referred from other neurology centres were examined in both departments and underwent surgery only with the confirmation of the above-mentioned departments. Patients with poor generalized myasthenic conditions were examined in both departments and recommended for IVIG treatment prior to surgery.

Operative technique

Anaesthetic management

All paediatric patients were preoperatively assessed by an experienced anaesthetist for MG. A lung isolation technique was also decided upon during the preoperative evaluation.

All patients received their usual dose of pyridostigmine on the day of surgery, but received no other premedication. An electrocardiogram, non-invasive blood pressure, pulse oximetry (Primus; Dräger, Lübeck, Germany) and neuromuscular function (TOF-Watch S monitor; Organon, Dublin, Ireland) were monitored in the operating room. Anaesthesia was induced with propofol (2–2.5 mg/kg) and fentanyl (2 mg/kg). Following the calibration of the train-of-four (TOF) monitor, the baseline TOF value was recorded and an initial rocuronium dose of 0.3 mg/kg (1XED95) was injected. Tracheal intubation was achieved via a single lumen tube for patients below 30 kg (n = 4). Fibre-optic bronchoscopy was used for the bronchial blocker (Fuji®; Fuji Systems, Tokyo, Japan) insertion for lung isolation. Double lumen tubes (Mallinckrodt Medical, Athlone, Ireland) (28 or 32 Fr) were used for the majority of children above 30 kg (n = 36) for lung isolation.

Surgical technique

Our surgical technique was defined elsewhere [11]. Briefly, a 30° camera was used. A right-sided operation is preferred because of the landmarks of the right hemithoracic cavity, such as the superior vena cava and phrenic nerve, and the fact that the right cavity is larger than the left one. The patient was positioned supine with supporting beanbags under his right chest and the table was rotated 30° to the surgeon's side. Three thoracoports (two 10 mm and one 5 mm) were placed around the mammary gland, taking care not to violate mammary tissue, especially in female patients. We prefer to place the ports according to the size and shape of the mammary gland (Fig. 1). Energy devices and endoscopic instruments were used to dissect out the gland from the pericardium and sternum. The right side of the mediastinal pleura was incised completely from top to bottom, and the plane between the anterior of the gland and the posterior of the sternum was fully visualized. The contralateral pleura were then opened into the left hemithorax both from above and under the left side of the thymus. When the left pleural space was opened, the endotracheal tube was temporarily disconnected, allowing the left lung to collapse and permitting a safe incision to be made along the left mediastinal pleura under the left side of the sternum. The left mediastinal pleura were taken into the specimen. The left phrenic nerve was visualized by pulling the left side of the thymus towards the surgeon. The dissection of the venous tributaries to the brachiocephalic vein requires the utmost care and is most susceptible to surgical error. The superior vena cava was mobilized away from the gland to expose the left brachiocephalic vein. Small thymic veins originating from the superior vena cave were dissected and clipped or divided by energy devices. These venous tributaries can be easily avulsed and can lead to troublesome bleeding. The superior pole was retracted with a moderate amount of tension. The left upper pole was dissected in a similar fashion. The thymic vein was either clipped or divided with energy devices. After these manoeuvres, the mediastinum was examined carefully, and frozen-section analyses were used if suspicious tissue was present (Fig. 2). The brachiocephalic vein, superior vena cava, aorta and the pulmonary arteries were clearly visualized. The fatty tissue at the cardiophrenic angle was dissected completely at the right and at the left.

Figure 1

Figure 2

Postoperative care

At the end of surgery, all patients received sugammadex (2 mg/kg) to reverse the neuromuscular block. If neuromuscular recovery was achieved (TOF ratio, >90%), the subjects were extubated in the operating room. If complete recovery was not ensured, mechanical ventilation was continued in the recovery room for several hours. Patients who required mechanical ventilation support were transferred to the intensive care unit.

Postoperative analgesia

All children received 10 ml/kg paracetamol with anaesthetic induction as well as an intercostal block to the surgical field with 10–20 ml of bupivacaine hydrochloride. Morphine was the rescue analgesic, with an initial dose of 0.05 mg/kg.

RESULTS

The mean age was 14.8 years (range, 8–18 years); 27 (67.5%) of the patients were female, and 13 (32.5%) were male. Of all of the patients, 23 (57.5%) were Osserman 2A, 11 (23.5%) were Osserman 2B and 6 (15%) were Osserman 3. Electromyography was positive in 30 (75%) patients, acetylcholine receptor antibody test was positive in 27 (67.5%) patients and the mean QMG was 11.5. All patients were treated with pyridostigmine bromide, with an average dosage of 209 ± 112 mg/day. Eleven (27.5%) patients also received corticosteroid medication and 22 (55%) patients received intravenous immunoglobulin treatment prior to the surgery. Chest computed tomography scans demonstrated normal mediastinum in 9 (22.5%) patients and thymic hyperplasia in 31 (77.5%) patients. The average time between the diagnosis and thymectomy was 15.9 ± 28.9 months (Table 1). None of the patients experienced a myasthenic crisis.

Table 1:

Demographics of the 40 paediatric MG patients

Sex, n (%)
 Male 13 (32.5)
 Female 27 (67.5)
Age, mean ± SD (range, years) 14.8 ± 2.2 (8–18)
Modified Osserman–Jenkins score, n (%)
 Class 2 23 (57.5) patients
 Class 3 11 (27.5) patients
 Class 4 6 (15) patients
BMI, mean ± SD (range) 22.3 ± 2.1 (15.0–35.5)
Anti-acetylcholine receptor antibody, n (%)
 Positive 27 (67.5)
 Negative 10 (25)
 Unknown 3 (7.5)
EMG, n (%)
 Positive 30 (75)
 Negative 7 (17.5)
 Unknown 3 (7.5)
Duration of disease from diagnosis to surgery, mean ± SD (range, months) 15.9 ± 28.9 (2–144)
Pyridostigmine median, mean ± SD (range) 209 ± 112 mg/day (60–420)
QMGs 11.5 ± 5.3 (5–25)
Radiology (thorax CT), n (%) Normal: 9 (22.5)
Thymic hyperplasia: 31 (77.5)

MG: myasthenia gravis; SD: standard deviation; BMI: body mass index; QMGs: quantitative MG score; CT: computed tomography.

All of the operations were completed with VATS. There were no perioperative events, and the average duration of the operation was 48.9 ± 31.3 min (range, 25–180 min). One (2.5%) patient required 18 h of mechanical ventilation postoperatively. Three (7.5%) patients developed complications (1 reintubation, 1 redrainage and 1 atelectasis requiring bronchoscopy). The average duration of drainage was 20.5 ± 12.1 h. The average pain level using the VAS was 2.3 ± 1.2 (range, 1–6). The average time of discharge was 1.8 ± 1.0 days (range, 1–5 days) (Table 2). The histopathological evaluation revealed lymphoid hyperplasia in 8 patients, true hyperplasia in 25 patients and normal thymic tissue in 7 patients.

Table 2:

Outcomes of the VATS thymectomy operation

Mean operation time, mean ± SD (range, min) 48.9 ± 31.3 (25–180)
Mean chest tube duration, mean ± SD (h) 20.5 ± 12.1
Mean length of hospital stay, mean ± SD (range, days) 1.8 ± 1.0 (1–5)
Mean VAS pain scale, mean ± SD (range) 2.3 ± 1.2 (1–6)
Complications, n (%) 3 (7.5%) (1 reintubation, 1 redrainage and 1 atelectasis requiring bronchoscopy)
Mean operation time, mean ± SD (range, min) 48.9 ± 31.3 (25–180)

VAS: visual analogue scale; VATS: video-assisted thoracoscopy; SD: standard deviation.

DISCUSSION

MG is a chronic disease characterized by weakness and rapid fatigability of voluntary muscles. Myasthenic patients can have high morbidity and mortality rates if left untreated. Some paediatric MG patients do not respond to the standard medication, and they require immunological therapies. Because of the possible morbidity and unaesthetic incision associated with sternotomy, a thymectomy is rarely considered as a therapeutic option in the MG paediatric population. Few alternatives to sternotomy are VATS and cervical thymectomy. Cervical thymectomy has been reported to have a higher risk for incomplete removal of the thymus. Cited concerns with the transcervical approach include: a comparatively less radical resection of thymic tissue due to limited access to the most caudal and lateral extents of the anterior mediastinum, which is conceptually less desirable due to an association with poorer outcomes; the unique nature of this approach makes it difficult to teach, learn and consistently reproduce, and therefore has limited adoption; and the neck incision may not be considered as cosmetically acceptable [12].

Based on the literature, it is unclear whether thymectomy could be a treatment option for paediatric patients. However, a recent study demonstrated the effectiveness of the thymectomy operation in juvenile MG patients [1]. In adult population, VATS thymectomy provides better long-term outcomes and quality of life compared with open surgery [13]. Also, it is well known that, in the adult MG population, corticosteroid doses can be reduced or stopped after thymectomy. Even if our study does not include long-term data, it is clear that the important issues in treating paediatric MG patients are to use a technique that is safe, less painful, complete and aesthetic and requires only a short hospital stay. A surgical technique without these capabilities would not be popular, especially in the predominantly female paediatric patient population.

Wagner [14] reported that open surgery and thoracoscopic procedures were associated with equivalent long-term symptomatic improvement, but that the thoracoscopic approach was associated with significantly less blood loss, a shorter hospital stay and a decreased requirement for postoperative narcotic analgesia. Christison-Lagay [10] recently reported that the thoracoscopic thymectomy is a safe operation with minimal morbidity that is successful in improving MG symptoms. In this study, the thoracoscopic thymectomy resulted in a decrease in the amount of medication, length of hospital stay and admission-related hospital expenses, and a reduced or similar operative time compared with that reported for a historical series of open thymectomies.

We previously demonstrated that a certain group of VATS thymectomy patients (33.7%) could be discharged the morning following surgery [15]. VATS thymectomy could also be considered as a model of fast-track surgery, as demonstrated by our patients with a mean 1.8-day discharge period and short duration of drainage time. However, this operation requires a steep learning curve for surgeons and is one of the most dangerous operations in an unexperienced surgeon's hands. We did not experience any major surgical trouble in our paediatric patients, but among all of the patients who underwent surgery for MG in our thoracic surgery department between June 2002 and April 2013, 1 experienced cardiac arrest, 1 had aortic rupture and 2 had vena cava injuries. For these 4 patients, we converted to open surgery. We recommend that the surgeon be ready for the possibility of open conversion in case a major problem occurs.

Seguier-Lipszyc [8] recommended performing left-sided thoracoscopic thymectomy. He claimed that a left-sided thoracoscopic approach gives a good mediastinal and cervical exposition. The only problem with a right-sided approach is the possible inadequacy of visualization of the left phrenic nerve. During a thymectomy, the left phrenic nerve should be seen and dissected meticulously to prevent an injury to the nerve. By using a grasper in the left hand to pull the left half of the thymus towards themselves, the surgeon can view the phrenic nerve via the camera and dissect the thymus and fatty tissue away from the left phrenic nerve. We prefer to use energy devices for this purpose.

With respect to long-term results, the neurologists followed these patients, recorded the examination findings and shared the results with us in interdisciplinary meetings. To demonstrate real benefits, patients should be examined before and after their operation. It is important to conduct the follow-up examination in the same amount of time after the ingestion of pyridostigmine bromide as that of the preoperative examination. MG has periods of exacerbations and remissions; thus, the duration of the postoperative follow-up period must be long enough to evaluate the benefits of thymectomy.

Our article has several limitations including the long-term benefits of thymectomy (as described above), its retrospective nature, lack of open cases for comparison (to demonstrate the real short-term benefits of this technique) and a small number of patients to find a statistical significance in terms of postoperative complications or hospital stay. The results in this paper may not reassure readers that VATS in these young patients offered an equivalent treatment of MG to open surgery, because neither short- nor long-term data were provided for open surgery in our population.

This study demonstrated that VATS thymectomy is a safe operation in patients younger than 18 years of age. It appears to be as effective as other surgical techniques in treating MG in the paediatric population. Short postoperative hospital stay (mean 1.8 days) and cosmetic incisions may increase the acceptance of VATS thymectomy by referring clinicians and patients' families.

Conflict of interest: none declared.

Yukarı