Thymectomy by thoracoscopic approach in myasthenia gravis



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Surgical Endoscopy

DOI: 10.1007/s00464-001-9114-6

© 2001 Springer-Verlag New York, Inc.

Thymectomy by thoracoscopic approach in myasthenia gravis


I. Popescu1, V. Tomulescu1, V. Ion2, and D. Tulbure3

1Department of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Sos. Fundeni 253, Sector 2, 72434, Bucharest, Romania

2Department of Neurology, Fundeni Clinical Institute, Sos. Fundeni 253, Sector 2, 72434, Bucharest, Romania

3Department of Anesthesia and Intensive Care, Fundeni Clinical Institute, Sos. Fundeni 253, Sector 2, 72434, Bucharest, Romania

Received: 4 July 2001; Accepted: 4 October 2001; Online publication: 31 December 2001


Abstract

Background: A series of 25 thoracoscopic thymectomies performed in the Department of General Surgery and Liver Transplantation of the Fundeni Clinical Institute between April 1999 and April 2000 is analyzed. Methods: Thoroscopic thymectomies were performed on 4 male patients (16%) and 21 female patients (84%), aged between 8 and 60 years. Results: The mean operative time was 90 (±15) min. There were no conversions to open thymectomy. Mortality was nil, and morbidity consisted of one minor postoperative right pneumothorax probably related to a injury to right mediastinal pleura that was not observed intraoperatively. Hospital stay ranged from 2 to 4 days, with a mean of 2.28 days. The patients were transferred to the neurological department and they were usually discharged after 1 more day. Conclusions: Postoperatively, all patients had clinical improvement of their disease both in symptoms and medication requirements, but a longer follow-up is necessary. The results are edifying regarding the very low morbidity, the lack of mortality, the acceptance of the patients, and the short hospitalization.

Keywords: Thoracoscopic approach, Thymectomy, Myasthenia gravis

Correspondence to: I. Popescu — Email: fundenip@com.pcnet.ro

Myasthenia gravis (MG) is a heterogeneous disorder with a protean, clinical, pathologic, and immunobiological picture [2 ] Until 1960, the pathogenesis of MG was unknown, although the thymus gland was determined to be involved by empiric observations of the beneficial effect of thymectomy. The autoimmune origin of the disease was suggested for the first time by Simpson [22], but Almon and colleagues [1 ] were the first to demonstrate circulating antibodies to acetylcholine receptor (AchR) sites of the neuromuscular junction. Elevated antibody levels are found in approximately 90% of patients and are roughly correlated with the clinical severity of the disease [2]. As Williams and Lenon [23 ] showed, the thymus is evidently implicated in the production of not only these end-plate antibodies but also striated muscle antibodies through some aberration in its normal function.

Today it is considered that the necessary and effective treatment of MG must include both mixed immunosuppression and surgery [1, 2, 22, 23]. Since the first case reported by Schumacher and Roth [21 ], the role of thymectomy in MG treatment has been well established. The main study demonstrating -the benefit of thymectomy in MG was that of Buckingham and associates [3], who compared the clinical course of patients after thymectomy with a computer-matched cohort receiving medical therapy.

After the success of laparoscopy in abdominal surgery, the miniinvasive access opened new possibilities in thoracic surgery. The principle of lessening the morbidity of a surgical procedure by minimizing the access trauma necessary to accomplish the desired operation was successfully applied to a wide variety of thoracic diseases. In 1992, Landrenau et al. [13] and Lewis et al. [14] and in 1993, Hazelrigg et al. [8], and Naunheim and Andrus [18 ] reported their experience using the miniinvasive approach [video-assisted thoracoscopic surgery (VATS)] on some mediastinal lesions. Yimm et al. [24], Mack et al. [15], and Mineo et al. [16], were the the first to report series of thoracoscopic thymectomies and their results.


Materials and methods


Between June 1989 and April 1999, in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute, 64 thymectomies were performed using the transsternal approach. The first thoracoscopic thymectomy (VATS) was performed in April 1999 by Popescu and colleagues. Since April 1999, all patients with nonthymomatous MG or with stage I thymoma [tumor less than 4 cm with no signs of invasiveness on computed tomography (CT)] have undergone the thoracoscopic approach, and patients with thymoma stage II or III have undergone the transsternal approach.Between April 1999 and April 2000, the thoracoscopic approach was used on 25 patients, whereas 5 patients with tumor larger than 4 cm or with signs of invasiveness on CT were assigned to open thymectomy. All patients were previously treated in the neurological department of the Fundeni Clinical Institute for at least 3 months. The diagnosis of MG was based on clinical signs and one or more of the following: response to edrophonium chloride, results of electromyography, and the presence of circulating antibodies against the AchR. A myasthenia deficiency score (MDS), proposed in 1975 by V. Ion and A. Cinca [9 ], was calculated in correlation with a striate muscular effort test. The maximal myasthenia deficit is 50 points according to this score; the striate muscles of the head represent 20 points and the spinal innervated muscles 30 points. The MDS was reduced to less than 10 points by medical treatment before surgery.

The medical treatment consists of anticholinesterase drugs, steroids, and immunosupression. Patients with severe symptoms, considered at risk for postoperative respiratory failure, underwent plasma exchange prior to operation (three cases, 12%).

For the clinical assessment of disease severity, a modified Osserman classification was used:


  • Class 1 (1)ocular myasthenia only

  • Class 2 (IIa)mild generalized myasthenia with ocular involvement

  • Class 3 (IIb)moderately severe generalized myasthenia with ocular involvement and mild bulbar symptoms

  • Class 4 (III and IV)acute severe myasthenia developing over a period of weeks or months with severe bulbar symptoms and late-onset severe myasthenia with severe bulbar involvement and gradual development from classes I and II

Our standard procedure was not to operate on patients in modified Osserman class 1 (I). Twelve patients (48%) in modified Osserman class 2 (IIa), 12 patients (48%) in modified Osserman class 3 (Il), and 1 patient (4%) in modified Osserman class 4 have been operated on.

The timing of surgery was determined in consultation with the neurologist. Preoperative diagnostic tests included spirometry and CT scan in all patients. Anticholinesterase drugs and steroid treatment were given as needed before and after the surgical procedure.


Surgical technique


Thymectomy was performed with the patient under general anesthesia with double-lumen tube placement and lying in a 30° off-centre position. A left thoracic approach was used in all cases. Three flexible trocars were inserted into the left hemithorax.

The operator stays on the left side of the patient in a cephalad position to the cameraman. The monitor is on the right side of the patient. The first trocar (12–44 mm) is placed through the fifth or sixth intercostal space, between the middle and posterior axillar lines. Pleural cavity exploration is facilitated by the selective right bronchus intubation, which allows the left lung to collapse. The pulmonary collapse may also be facilitated by gas insufflations at a maximum of 5 mmHg pressure for 5 min. The second and third trocars (12–14 and 5–7 mm, respectively) are placed through the third intercostal space on the anterior axilary line and through the fourth or fifth intercostal spaces on the midclavicule line. After a careful pleural cavity exploration, we spot the anterior mediastinum. There are two important anatomical marks for the anterior mediastinum: the phrenic nerve and the internal thoracic artery.

The incision of the mediastinal pleura and the dissection of the thymus begin anterior to the left phrenic nerve and continue into the entire thyrmic compartment. The cranial limit of the dissection, at the level of the mediastinal pleura, is the internal thoracic artery. The thymectomy represents the emptying of the lymphatic and fat tissue in the thymus compartment.

The use of the ultrascision scalpel (Harmonic Scalpel Ultrascision; Ethicon Endo-Surgery) facilitates the dissection, decreases the time of the intervention, and avoids the risks of the electrocoagulation in this area. The anterior, retrosternal dissection is the easiest part of the intervention. It starts from the pericardial plane and ends at the inferior neck limit. The posterior dissection also begins anterior to the phrenic nerve and continues posterior and inferior in the pericardial plane, overtaking the median line, to the right of the thymus gland. All anterior mediastinal tissue including the pericardial fat at the pericardiophrenic angle is included in the en bloc resection.

During the posterior dissection, the pericardium, the aortic arch, the left brachiocephalic vein, and the superior vena cava are visualized and cleaned of all fat tissue. The most difficult area to dissect is between the superior vena cava and the left brachiocephalic vein. At the superior pole, the dissection is performed in the anterior carotidal plane to the internal thoracic artery level. The left superior horn may occasionally pass behind, instead of in front of the brahiocephalic vein. The thymectomy ends with the identification of the superior part of the gland, the thireothymic ligament section, and freeing of the superior horns from the surrounding tissue. Cervical skin transillumination is the indication that the cervical limit of the dissection has been reached.

During the operation, we can visualize the superior, lateral, or medial arterial thymic pedicles. They are clipped and cut or ultrasonically coagulated. Dissection of the thymic veins is very important. The veins are very short and enter directly into the left brachiocephalic vein. Tearing out such a pedicle may cause a hemorrhage, which is very difficult to correct thoracoscopically. During the operation, the lung is periodically reventilated, and bronchial secretions are aspirated to reduce the risk of postoperative atelectasis. Thymus extraction is quite easily done by enlarging the hole of the second trocar port (the anterior one) and bagging the piece before extracting it.

The operation ends with the thymic cavity inspection, which can detect possible remnant tissue. Finally, we wash the cavity with warm saline. At the end of the operation we place two drains in the pleural cavity through the inferior trocar ports.

The therapeutic effect of thymectomy was established by comparing the preoperative clinical status with the status recorded every 3 months postoperatively. All patients have been followed from 6 to l8 months. Postoperative clinical status was rated based on changes in both symptoms and medication requirements.

Because of the need for universally accepted classifications and grading systems, we analyzed our series results retrospectively using the recommendations of the Thymectomy Task Force of Myasthenia Gravls Foundation in America (MGFA)[10].

Results


Four male patients (16%) and 21 female patients (84%), aged 8–60 years, underwent a thoracoscopic thymectomy. Using the MGFA [10] clinical classification (Table 1 ) prior to operation there were 8 patients (32%) in class IIa, 4 patients (15%) in class IIb, 7 patients (28%) in class IIIa, 5 patients (20%) in class IIIb, and 1 patients (4%) in class IVa.

Surgical results


There was no conversion to open thymectomy. No patients had phrenic or recurrent nerve injury, and no patients developed atelectasis or pneumonia postoperatively. The mean operative time was 90±15 min. All patients were extubated within 1 h after operation.

In one patient (4%) with organized pachipleural adhesions, pleuralisis was extremely difficult and time-consuming. Bleeding at the level of the trocar port occurred in two cases (8%); in one of these cases ligature of the intercostal artery was necessary. There was one minor postoperative right pneumothorax that was probably related to a right mediastinal pleural lesion that was not observed intraoperatively.

On average, postoperative hospital stay was 2 days in the general surgery department, and then the patients were transferred for 1 day to the neurological department. Hospital stay in the surgical department ranged from 2 to 4 days, with a mean of 2.28 days.

Clinical results


Regarding the MGFA MG therapy status (Table 2) [10 ], prior to operation all patients received prednisone (PR) therapy, 23 patients (92%) were on cholinesterase inhibitors therapy (CH) and 20 patients (80%) had been on lmmunosuppression therapy other than prednisone In two cases (8%) plasma exchange therapy, acute [PE(a)] (for exacerbations or preoperatively) was needed.

Postoperative MGFA MG therapy status at 3 months showed that 22 patients (88%) were on PR therapy, 17 patients (68%) were on CH therapy, and no patient needed IM or PE therapy. Postoperative MGFA MG therapy status at 6 months showed that 18 (72%) of patients were on PR therapy, 16 patients (64%) were on CH therapy, and 1 patient needed IM therapy.

The quantitative MG score for disease severity (QMG score; Table 3) [10] was calculated prior to operation (Fig. 1) and every 3 months after. The MGFA post intervention status [10 ] cannot be calculated because the minimum interval for follow-up is recommended to be 1 year, and the most recent followup of 19 patients (76%) occurred less then 1 year since surgery.

Pathologic examination of the specimens revealed the following: 3 patients (12%) had normal thymus, 5 patients (20%) had thymic hyperplasia,11 patients (44%) had thymic involution, and 6 patients (24%) had thymoma. The pathological examination in the thymoma cases showed a lymphoepitelial thymoma with lobular disposition in 4 cases (16%), malignant lymphoepitelial thymoma with calcification in 1 case (4%), and timolipoma in 1 case (1%). By the classification of Masaoka and colleagues all thymomas were stage I. The patient with malignant thymoma first underwent chemotherapy and then radiotherapy.


Discussion


The major issues for a surgeon who has an interest in thymectomy are related to patient selection and surgical technique. Regarding patient selection, in cooperation with the neurological department of our hospital, we decided to operate only on patients with generalized MG. We did not operate on patients with ocular symptoms alone, modified Osserman class 1 (I), although it is well-known that more than 30% of these patients will develop generalized MG [2, 5 ]. We also decided to operate on patients with late-onset MG only If the patients are younger than 70 years old and/or they have thymomatous MG. All patients were medically treated until the MDS was reduced at least to 10 points (QMG score at least 13 points). Figure 1 presents the evolution of QMG score from the highest values until operation and at 3 and 6 months.

Throughout the years, many approaches have been described, such as the transcervical approach [6, 7] the transsternal approach [12], the mixed transcervical and transsternal approach (the so called maximal thymectomy [4, 11] and the minimally invasive thoracoscopic approach (VATS)[15, 17, 24 ]. The maximal thymectomy is certainly the most radical and effective thymectomy, but in well-selected cases the results of transsternal thymectomy are similar to those obtained using the cervical or thoracoscopic approach and near to those obtained using the mixed approach, such as maximal thymectomy [15, 24].

Like the cervical approach, the thoracoscopic approach is associated with minimal thoracic trauma, low postoperative morbidity, short hospitalization time, and, most important, a high patient compliance at surgery compared with the transsternal approach[24 ]. The thoracoscopic approach has the advantages of the microinvasive surgery, with a good view and a simple technique, especially for a team well trained in advanced laparoscopic procedures. The instruments are not crowded on a single port and the monitor allows the entire surgical team to visualize the operation. Thoracoscopy permits very early recovery, with rapid reintegration into the working process. Long-term complaints after videothoracoscopy are rare.

We started using the thoracoscopic approach in 1999 after achieving significant experience in open thymectomy [20] and advanced laparoscopic procedures (splenectomy, colorectal, and hepatic laparoscopic surgery).

Yim and colleagues [24 ] first proposed a right-sided approach for VATS thymectomy and recommended this approach for several reasons: (1) identification of the vena cava is a land mark for easier dissection of innominate vein, (2) the confluence of the innominate veins is easier to dissect using a right approach, and (3) ergonomically it is easier for right-hand surgeons to dissect the thymus from inferior horns to upper horns in a right approach.

As Minneo and associates [17 ], we believe that thymectomy can be performed from either side. We believe that the dissection maneuvers are safer from the left because the superior vena cava lies outside of the surgical field, thus reducing the risk of an incidental lesion to this vessel, and dissection of the right part of the thymus is easier from the left approach than dissection of the left part of the thymus from the right approach.

In all instances, every effort was made to remove all thymic tissue as completely as possible by clearing the innominate vein and anterior pericardium from all resident mediastinal fat. We believe this is easier to perform using a left-side approach since, most of the mediastinal fat is located on the left part of anterior mediastinum. The use of a 30° scope (Karl Storz endoscope) significantly helps in these areas.

Opening of the right pleural cavity is not an accident. On the contrary, if the intention to remove all all thymic tissue as completely as possible calls for the resection of the entire right costomediastinal sinus (sparing the right phrenic nerve, of course), we perform this procedure and finish the operation with bilateral thoracic drainage. This has happened in two cases with thymomatous myasthenia.

We have not performed a pneumomediastinum to facilitate thymectomy, as have Minneo and colleagues [16], but we have seen that insufflation upto 5 mmHg facilitates pulmonary collapse, making mediastinal dissection easier.

Our surgical results, with no mortality and major morbidity are similar to those of Mack and colleagues [15] and Minneo and associates [17] and they compare favorably with 33% morbidity reported by Bulkley and colleagues[4] with transsternal thymectomy and with 9.52% in our historical series [20].

The mean duration of the disease until the patient underwent surgery in our series was 28.8 months, which compares favorably with the mean duration of 42.2 month in our historical series [20 ]. This indicates that the thoracoscopic approach has a high patient compliance at surgery because of its superior cosmetic results, with the same medical results.

Follow-up at 3 and 6 months showed a slow decrease in QMG score (normal in MG thymus surgery), but this was a good result considering the reduction of medical requirements.

The patient that needed an IM treatment had malignant thymoma, and at 6 months the QMG score was still high. CT scan has not shown any remnant thymus tissue. Reevaluation of the patient has shown multiple bone metastases and chemotherapy has started. In our series, the thoracoscopic thymectomy indications were for thymus dysplasia and stage I thymoma. We do not believe that the method is indicated in stage II or III thymoma, even; if technically possible [19], because the risk of major complications or incomplete resection is very high.

Postoperatively, all patients had clinical improvement in both symptoms and medication requirements, but the follow-up period is too short for conclusions. Larger series and longer follow-up are necessary to make definite conclusions. The results have to be analyzed using standardized methods. The guidelines of the Thymectomy Task Force of the M6FA [10 ] might be used to analyze and compare the results of thoracoscopic thymectomy versus other approaches. Our results are certainly conclusive regarding the very low morbidity, the lack of mortality, the acceptance of the patients, and the short hospitalization time.


References


1. Almon RR, Andrew AG, Appel SH (1974) Serum globulin in myasthenia gravis: inhibition of L-bulgaroton to acetylcholine receptors. Science J 186:55 [PubMed]

2. Beekman R, Kuks JB, Oosterhuis HJ (1997) Myasthenia gravis: diagnosis and follow-up of 100 consecutive patients. J Neurol 244:112-118 [PubMed]

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6. Calhoun RF, Ritter JH, Guthrie TJ, et al. (1999) Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients. Ann Surg 4:555-561 [PubMed]

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8. Hazelrigg SR, Mack MJ, Landrenau RJ (1993) Videoassisted thoracic surgery for mediastinal disease. Chest Surg Clin North Am 3:283-291 [PubMed]

9. Ion V, Cinca A (1981) Miastenia gravis. Tratat de neurologie, sub redactia C. Arseni, Ed Medicala :1109-1189 [PubMed]

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13. Landrenau RJ, Dowling RD, Castillo WM, Ferson PF (1992) Thoracoscopic resection of an anterior mediastinal tumor. Ann Thorac Surg 54:142-144 [PubMed]

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16. Mineo TC, Pompeo E, Ambrogi V, Sabato AF, Bernardi G, Casciani CU (1996) Adjuvant pneumomediastinum in thoracoscopic thymectomy for myasthenia gravis. Ann Thorac Surg 62:1210-1212 [PubMed]

17. Mineo TC, Pompeo E, Lerut TE, Bemardi G, Coosemans W, Nofroni I (2000) Thoracoscopic thymectomy in autoimmune myasthenia: results of left side approach. Ann thorac Surg 70:327-334 [PubMed]

18. Naunheim KS, Andrus CH (1993) Thoracoscopic drainage and resection of giant mediastinal cysts. Ann Thorac Surg 55:156-162 [PubMed]

19. Noda M, Matsumaray , Handa M, Tanita T, Fujimura S (1997) Video-assisted thoracoscopic surgery of bilateral dissemination of invasive thymoma: report of a case. Kyobu Geka 50:886-889 [PubMed]

20. Popescu I, Ion V, Tulbure D, Brasoveanu V, Hrehoret D, Popescu C (1998) Rolul timectomiei in tratamentul miasteniei gravis—experienta pe 42 de cazuri. J Chir Toracica 3:131-135 [PubMed]

21. Schumacher ED, Roth J (1912) Thymectomie bei cenem Fall von Morbus Basedowii mit Myasthenie. Mitt Gregzeb D Med Chir 25:746 [PubMed]

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24. Yim AP, Kay RLC, Ho JKS (1995) Video-assisted thoracoscopic thymectomy for myasthenia gravis. Chest 108:1440-1443 [PubMed]


Tables


Table 1. MGFA clinical classification

Table 2. MGFA MG therapy status



Table 3. Quantitative MG score for disease severity

Figures


Figure 1
Figure 1 (large scale)
Fig. 1. QMG scores before operation, an at 3- and 6- month follow up


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