Extended thymectomy through video assisted thoracic surgery and cervicotomy in the treatment of myasthenia

Abstracts

BACKGROUND: The relationship between myasthenia and the thymus is evident and the current treatment of this condition includes thymectomy. However, a revision of our experience with thymectomy has revealed the necessity of a more radical technique. OBJECTIVE: To analyze, retrospectively, myasthenia gravis patients who underwent videothoracoscopic radical thymectomy, emphasizing the advantages and drawbacks of the methodology, pathological findings and results related to disease control. MATERIAL AND METHODS: Twenty-one myasthenic patients (18 females and 3 males, aged 17 to 51 years), underwent videothoracoscopic bilateral thymectomy associated to transverse cervicotomy for removal of the thymus gland and surrounding tissues, and right and left pericardiac fat tissues. Those tissues were separately sent to pathology analysis. The mean time of follow-up was 39.2 months. RESULTS: There were no intra-operative deaths. Two patients (9.5%) suffered vascular injury, and one patient (4.8%) presented a low level permanent dysphonia. Nineteen patients (90.4%) are doing well, with none or low dose medications. Pathology studies showed 10 hyperplastic thymuses, 6 with involution and 5 with normal aspect. Ectopic thymic tissue was found in six patients (28.6%). CONCLUSION: Videothoracoscopic radical thymectomy offered a good control of myasthenia gravis. Additionally, ectopic thymus tissue was removed from some patients.

Thorax; Surgery, video-assisted; Myastenia gravis; Thymectomy

INTRODUÇÃO: A relação entre a miastenia e o timo é evidente e o tratamento atual desta condição inclui a timectomia. No entanto, uma revisão de nossa experiência com a timectomia revelou a necessidade do uso de uma técnica mais radical. OBJETIVO: Analisar retrospectivamente pacientes portadores de miastenia gravis que foram submetidos a timectomia radical por videotoracoscopia, ressaltando vantagens do método, complicações, análise histopatológica e resultados em relação ao controle da doença. MATERIAL E MÉTODO: Vinte e um pacientes miastênicos (18 do sexo feminino e três do sexo masculino, com idade variando de 17 a 51 anos) foram submetidos a timectomia por videotoracoscopia bilateral associada a cervicotomia transversa com ressecção da glândula tímica, dos tecidos peritímicos e das gorduras pericárdicas direita e esquerda. Todos os tecidos implicados foram analisados pela anatomia patológica separadamente. Houve acompanhamento por período médio de 39,2 meses. RESULTADOS: Não houve mortalidade operatória. Ocorreram duas (9,5%) lesões vasculares e um (4,8%) paciente passou a apresentar disfonia leve permanente. Dezenove (90,4%) pacientes estão com boa evolução, sem medicação ou com dose reduzida da mesma. A histopatologia demonstrou 10 hiperplasias do timo, seis involuções tímicas e cinco timos normais. A presença de tecido tímico ectópico foi detectada em seis (28,6%) pacientes. CONCLUSÃO: A timectomia radical por videotoracoscopia ofereceu bom controle da miastenia gravis. Fez-se ressecção de tecido tímico ectópico em alguns pacientes.

Tórax; Cirurgia assistida por vídeo; Miastenia gravis; Timectomia

ORIGINAL ARTICLE

Extended thymectomy through video-assisted thoracic surgery and cervicotomy in the treatment of myasthenia^*

Eduardo Haruo Saito^I (te-sbct); Cláudio Higa^II (te sbct); Rodolfo Acatauassu Nunes^III (te-sbct); Gérson C. Magalhães^IV; Luiz Carlos Aguiar Vaz^V; Vicente Faria Cervante^VI

^IPh.D., Adjunct Professor in the Thoracic Surgery Department and Specialist as designated by the Brazilian Society of Thoracic Surgery

^IIAssistant Professor in the Thoracic Surgery Department and Specialist as designated by the Brazilian Society of Thoracic Surgery

^IIIPh.D., Adjunct Professor in the Thoracic Surgery Department and Specialist as designated by the Brazilian Society of Thoracic Surgery

^IVFull Professor in the Neurology Department

^VPh.D. and Adjunct Professor in the Pathology Department

^VIAdjunct Professor in the Nephrology Department

^{Correspondence}

ABSTRACT

BACKGROUND: There is an obvious relationship between the thymus and myasthenia. Current treatment for this condition includes thymectomy. However, a review of thymectomy outcomes has revealed the need for a more radical technique.

OBJECTIVE: To analyze, retrospectively, myasthenia gravis patients who underwent video-assisted thoracoscopic radical thymectomy, emphasizing the advantages and drawbacks of the methodology and evaluating pathological findings and treatment outcomes.

MATERIAL AND METHODS: A total of 21 myasthenic patients (18 females and 3 males, aged 17 to 51 years) underwent video-assisted thoracoscopic bilateral thymectomy in combination with transverse cervicotomy in which the thymus gland, surrounding tissues, and right and left pericardial adipose tissues were all removed. The adipose tissues were sent for separate pathology analyses. The mean follow-up period was 39.2 months.

RESULTS: There were no intraoperative deaths. Of the 21 patients, 2 (9.5%) suffered vascular injury, 1 (4.8%) presented permanent low-level dysphonia, and 19 (90.4%) are doing well, maintained on low-dose medication or no medication. Pathology revealed 10 hyperplastic thymuses, 6 with involution and 5 with normal aspect. Ectopic thymic tissue was found in 6 (28.6%) of the patients.

CONCLUSION: Video-assisted thoracoscopic radical thymectomy offered good control of myasthenia gravis. In some cases, removal of ectopic thymic tissue is also recommended.

Key words: Thorax. Surgery, video-assisted. Myasthenia gravis. Thymectomy.

FEV₁ – Forced expiratory volume in the first second

ICU – Intensive Care Unit

MG – Myasthenia gravis

SUS – Sistema Único de Saúde (Brazilian Public Health System)

VATS – Video-assisted thoracic surgery

Introduction

Myasthenia gravis (MG) is an autoimmune disease that arises from pathological changes at the neuromuscular junction. Clinically, it is characterized by abnormal and prolonged fatigue of the striated muscles, aggravated by repetitive motions or tension and improving with rest or with the use of cholinesterase inhibitors. The relationship between the thymus and myasthenia is evident and current treatment of its generalized form includes thymectomy.

After review of thymectomy outcomes at the Hospital Universitário Pedro Ernesto, it became evident that a more radical method should be adopted. Thymectomy using the transcervical approach produced little benefit (38.5% of patients presented residual thymic tissue and required a second operation).⁽¹⁾ Residual thymic tissue after transcervical resection has also been found by other authors such as Henze et al. (27% of patients presenting residual thymic tissue and requiring a second operation), Masaoka et al. and Mineo et al.^(2-4) Mineo et al. performed the second surgery using video-assisted thoracoscopy.

Video-assisted thoracic surgery (VATS) presents a new treatment option, allowing for a more radical resection without the need for sternotomy.

Since some patients improve immediately after the surgery and others may take up to 10 years to experience any benefit, an extended follow-up period is necessary to analyze the results of thymectomy in the control of MG. The primary objective of this study was to analyze, retrospectively, patients submitted to thymectomy involving VATS, highlighting the advantages, complications, histopathological analysis and efficacy of MG control.

Methods

We studied 21 myasthenic patients who underwent extended thymectomy at the Hospital Universitário Pedro Ernesto/UERJ, and who were monitored through the Thoracic Surgery and Neurology outpatient clinics from May 1996 to May 2000. These patients all had MG without thymoma. Extended thymectomy was defined as the resection not only of the thymus gland but also of the right and left pericardial adipose tissues. This was done in combination with cervical exploration in order to remove ectopic thymic tissue (thymic tissue found outside the thymus gland). Patient age ranged from 17 to 51 (mean: 29.7 years). Of the 21 patients studied, 3 (14.3%) were male and 18 (85.7%) were female. The Osserman system of MG classification was used to define our patients as either class II A (2 patients) or class II B (19 patients), the latter being characterized as generalized MG with muscular and bulbar involvement.⁽⁵⁾ We used the scale proposed by Calhoun et al. to assign numeric values describing the degree of MG symptoms: 0 = asymptomatic; 1 = ocular signs and symptoms; 2 = mild generalized weakness, 3 = moderate generalized weakness or bulbar dysfunction; 4 = severe generalized weakness or respiratory dysfunction.⁽⁶⁾ The pre-operative mean was 2.95.

We gave the patients detailed information on the new technique and all of them agreed to undergo the operation, aware of the possibility that sternotomy might be necessary if the resection was not possible or if some complication arose. This new approach had been previously approved by the Scientific Committee (063/1996).

Once a diagnosis of MG had been established, the 19 patients who had the generalized form were sent from the Neurology Department to the Thoracic Surgery Department to be prepared for the operation. Pre-operative laboratory work-ups were performed. At the time of surgery, a combination of an anticholinesterase (pyridostigmine bromide) and corticoids (prednisone), both given in dosages determined by the number and degree of clinical manifestations, was being used to control the disease in all patients.

As an additional pre-operative measure, class II B patients were submitted to 2 to 3 sessions of plasmapheresis, 24 hours apart, the last being on the day before the surgery. The pre-operative preparation typically lasted for 3 days.

All patients were intubated with a double-lumen endotracheal tube.

The patients were placed in dorsal decubitus with arms outstretched. The right hemithorax was approached first, and then the left hemithorax. A metal arch was positioned 40 cm above the sternal notch and used to support the sternum elevator (Figure 1).

The procedure was carried out by 2 teams, one at the head and the other at the right side of the operating table. Cervical dissection was performed through a 6 to 8 cm anterior transversal incision, 2 cm above the sternal notch. Video-assisted thoracoscopy, initially on the right and then on the left side, was performed using 10-mm trocars, 1 between the midclavicular line and the anterior axillary line at the second intercostal space, and the other two at the third and fifth intercostal spaces, respectively, along the anterior axillary line. In addition to the thymus gland, pericardial fat and all extraneous thymic tissue were removed bilaterally as has been previously described.⁽⁷⁾ All resected tissues were removed through the cervical incision. During the surgery, the phrenic nerve was monitored and carefully preserved.

Results

There were no intraoperative deaths. The median length of surgery was 210 minutes. There were 2 patients (one presenting pneumonia) who required post-operative ventilatory support and remained in the intensive care unit (ICU) for extended periods (60 days and 15 days). All the other patients were extubated in the operating room and spent approximately 24 hours in the ICU or recovery room. Typically, drains were removed 2 days after the surgery. The mean post-operative hospital stay was 7.6 days (mean of total days hospitalized: 12.6).

Pain was easily controlled with analgesics such as dipyrone or paracetamol (acetaminophen) and non-steroidal anti-inflammatory agents, which were regularly given in the first two days of the post-operative period. This analgesia regimen was administered to all patients, in combination with intercostal nerve blocks (corresponding to the perforations made by the trocars) with 0.5% bupivacaine.

In the first days of the post-operative period, 6 patients presented dysphonia. In 5 of the 6, their condition improved progressively, while remaining unchanged in 1 patient. The laryngoscopy of these patients showed left vocal cord paralysis and the dysphonia improved partially after phonology sessions. In patients who had transient dysphonia, laryngoscopy was not performed.

Vascular lesions, created during cervical resection, were observed in 2 (9.5%) of the 21 patients. In 1 patient (previously submitted to supra-sternal thymectomy, still presenting residual thymic tissue and showing no clinical improvement), sternotomy was needed in order to repair a lesion of the innominate artery. In the other patient, a lesion of the left internal thoracic vein was repaired through cervicotomy.

Medication used for the control of MG was reintroduced on the first post-operative day for all patients.

The follow-up period ranged from 12 to 65 months (mean: 39.2 months). Of the 21 patients, 19 (90.4%) presented good outcomes (easy clinical control). Within those 19, 3 required no further medication, 15 required lower doses of medication and 1 patient is being maintained on a dose identical to the pre-surgery dose. These 19 patients are all currently asymptomatic or presenting few symptoms. The remaining 2 patients (9.5%) presented no improvement after thymectomy and their conditions worsened. In 1 of these patients, a urinary infection provoked a myasthenic crisis and the patient died in the fourth month after surgery. This was a patient who previously undergone a transcervical thymectomy and was selected for this second operation due to the presence of residual thymic tissues.

The tissue samples removed during surgery (thymus, right pericardial adipose tissue, left pericardial adipose tissue and other surrounding thymic tissues) were sent for individual pathology analysis. The thymus was carefully separated from the pericardial adipose tissue so that no cases of gland fragmentation with adipose tissue and surrounding thymic tissues were observed. Histopathology revealed that, of the 21 thymuses, 10 (47.6%) were hyperplastic, 6 (28.6%) were involuted and 5 (23.8%) were normal.

A very interesting finding was the presence of ectopic thymic tissue (determined not to be gland fragments) in 6 (28.6%) of the patients. In 5 cases, this tissue was observed within the left pericardial adipose tissue, and in the other case, it was found in the right and left pericardial adipose tissue and in the cervical region (Figures 2 and 3).

Discussion

Thymectomy is usually indicated for patients with generalized MG who require incremental increases in their medication (thereby increasing the risk for adverse side effects) or who respond poorly to those medications and suffer myasthenic crises.⁽⁸⁾

Transcervical thymectomy, consisting of thymus resection through a cervical incision, is a technique used by some surgeons. The reported advantages are early mobilization in the post-operative period, minimal pain and good control of MG in up to 90% of the cases with few complications and outcomes comparable to those of thymectomy through sternotomy.^(6,9) Some surgeons point out that the main disadvantage of this approach is incomplete removal of the thymus (usually due to fragmentation, occasionally leaving entire lobes intact), resulting in continued myasthenic states and requiring a second operation in 20% to 30% of cases. ^(3,10)

Thymectomy can also be performed through total or partial sternotomy, with or without the opening of the pleurae and sometimes in combination with cervical exploration. In partial sternotomy, positive outcomes are achieved in up to 85% of cases.^(11,12) Among the various thymectomy methods, the only one which allows complete resection is the one proposed by Jaretzki et al. ("maximal" thymectomy through cervicotomy and median sternotomy), who reported good outcomes in 96% of cases.⁽¹³⁾ Based on those findings, an alternative technique for achieving complete resection without sternotomy has been proposed, namely extended thymectomy using video-assisted bilateral thoracic surgery in combination with transverse cervicotomy.

After surgery had been performed on the first 4 patients involved in this study, we found, in the medical literature, a description of a similar technique with slight differences in the placement of the trocars.⁽¹⁴⁾ We were less concerned with originality than with finding the ideal technique for performing extended thymectomy (using VATS) in MG patients.

Using only video-assisted thoracoscopy without cervicotomy, identification of ectopic thymic tissue would be difficult. As has been stated by Jaretzki et al., in addition to extended thymectomy, cervicotomy is necessary to explore all possible locations of ectopic thymic tissue.⁽¹³⁾ Another important aspect of this technique is the ease of dissecting the superior lobes of the thymus, cutting the right and left thyrothymic ligaments near the thyroid and verifying that no thymic tissue remains in the region. However, some surgeons perform thymectomy without cervicotomy and report good liberation of the superior poles up to the neck through blunt dissection.^(15,16)

In video-assisted thoracoscopy used for resection of the thymus gland alone, access is gained through either side, although right-side access is more frequent.^(15-17) In left-side access, the thymus may be removed, but it is not possible to perform bilateral resection of the mediastinal and pericardial adipose tissues, where potentially ectopic thymus tissue may be found. According to Jaretzki et al., such tissue is present in 52% of patients.⁽¹³⁾ Removal of the adipose tissue is fairly straightforward. Once in the correct plane, simple blunt dissection will detach the adipose tissue from the pericardial surface without excessive bleeding, since there are few large-caliber vessels in the region.

The use of multiple angles of view (left and right video-assisted thoracoscopic and transcervical) is important for complete removal of the thymus. If there is accidental lesion of the gland, as occurred in 3 patients in the present study, the fragment may be easily removed together with the pericardial adipose tissue. In those 3 cases, the fragments were carefully separated into thymic tissue and adipose tissue. In all cases, the thymus and the pericardial (right and left) adipose tissue were sent for separate histopathological analyses. The presence of thymic tissue in the pericardial adipose tissue in 6 of our patients supports the findings of Jaretzki et al.⁽¹³⁾

When the various methods are compared in terms of time in the operating room and length of hospitalization, it is obvious that less invasive surgeries such as transcervical thymectomy require less surgical time (average: 104 min) and shorter hospital stays (average: 1 day).⁽⁶⁾ More time is needed for the execution of and recovery from extended thymectomy using techniques such as left VATS (average surgical time: 148 min.; average hospital stay: 5.2 days) and total cervicotomy/sternotomy (average surgical time: 163 min.; average hospital stay: 5.8 days).^(16-20) In our case, the average duration of surgery was 360 min in the first patients and 180 min in the others (average surgical time: 210 min.; average hospital stay: 12.6 days) The longer hospital stays were due to the 3 pre-operative plasmapheresis sessions, 24 hours apart, which were performed in 19 patients and to the fact that 2 patients remained in the ICU for extended periods.

The main reason for the longer duration of surgery, especially in the first patients, was the difficulty encountered in the placement of the trocars. Frequently, the procedure had to be interrupted due to selective ventilation and hypoxia, and the collapsed lung had to be ventilated. Continuous positive airway pressure, maintaining a constant flow of oxygen to the collapsed lung, was used to correct this problem. However, the continuous positive pressure was occasionally discontinued, since the inflated lung made the surgery difficult.

Plasmapheresis was used in 19 patients whose muscles with bulbar innervation (swallowing and breathing) were affected. Of those, 17 were extubated in the operating room. The use of plasmapheresis in the pre-operative period of myasthenic patients contributed to a significant reduction in mechanical ventilation times in the post-operative period and shorter stays in the recovery units, similar to that seen in studies by D’Empaire et al. and Yusta et al. ^(21,22).

No patients complained of pain related to compression of intercostal nerves caused by manipulation of the trocars during surgery. In all patients, blocking the intercostal nerves with 0.5% bupivacaine protected against that complication, which is common after video-assisted thoracoscopy.^(23,24) Neither were there any complaints of pain related to the use of bilateral drains (we used 28 to 30 FR drains). The drains were withdrawn between the second and third post-operative days. The ease of controlling pain in the post-operative period was also observed by Novelin et al.⁽¹⁴⁾

In the 95 thymectomies through cervicotomy performed by Jaretzki et al., several complications were found.⁽²⁵⁾ Infections (bilateral empyema and sternal osteomyelitis) developed in 2 patients, 2 other patients developed post-pericardiotomy syndrome, 1 presented dehiscence of the sternum, 1 suffered bilateral quilothorax and 1 had a pulmonary embolism. Complications related to surgical access (osteomyelitis and sternal dehiscence) were not found in our cases since we did not open the sternum.

In the present study, the 9.5% rate of hemorrhagic complications is attributable to accidents occurring as a result of cervical dissection and not as a result of video-assisted thoracoscopy. The most severe such accident occurred during sternotomy repair in a patient who had had a previous operation (in which transcervical resection failed). A study by Papatestas et al. showed that, of the first 15 patients submitted to transcervical thymectomy, 3 (20%) had vascular lesions and required sternotomies.

Dysphonia (1 transient and 5 persistent) occurred as a result of the attempt to achieve maximum resection through cervicotomy. There have also been reports of such complications in transcervical surgeries and sternotomy.^(32,33) Bulkey et al. reported 4 cases of dysphonia (3 persistent and 1 transient) after "maximal" thymectomy through cervicotomy/sternotomy.⁽²⁰⁾ After a median follow up of 39.2 months, clinical control was facilitated in 90.4% of these cases, showing that this method produces encouraging outcomes. Mategazza et al. studied 101 patients submitted to extended thymectomy (using bilateral video-assisted thoracoscopy in combination with transverse cervicotomy) and observed a 70% rate of complete remission and pharmacological remission in.⁽²⁶⁾ in a study of 33 patients submitted to right VATS, Mack et al. observed good outcomes in 87.9%. ⁽²⁷⁾ In patients submitted to left VATS, Mineo et al., reported positive outcomes in 96% of cases. ⁽¹⁸⁾

Rückert at al. performed a prospective and randomized study comparing the lung functions vital capacity, functional vital capacity, forced expiratory volume in the first second (FEV₁) and peak flow in 20 patients, 10 submitted to left VATS and 10 to thymectomy by total sternotomy.⁽²⁸⁾ In the post-operative period, they observed a 35% reduction in the lung function of patients submitted to thymectomy by VATS and a 65% reduction in patients who underwent sternotomy. Less reduction in lung function and shorter recovery times were seen in the patients submitted to VATS. In addition, these patients suffered less pain, which is a considerably relevant factor.

In the present study, 1 of the 2 patients who responded poorly to radical thymectomy had hyperplastic thymic tissue amidst the left pericardial adipose tissue. The other was the only patient who had previously (5 years prior) undergone VATS. The decision to perform the second thymectomy was made based on the presence of residual thymic tissue and a worsening of her myasthenia. The clinical importance of this finding has been elaborated upon by Ashour et al., who observed poorer post-operative responses in patients who presented ectopic thymic tissues.⁽²⁹⁾ Scelci et al., using extended thymectomy with bilateral video-assisted thoracoscopy in combination with transverse cervicotomy, reported ectopic thymic tissue in the pre-tracheal region in 14.8% of cases and in the anterior mediastinum in 33.3%.⁽³⁰⁾ Mineo at al. found ectopic thymic tissues in 32.3% of patients submitted to left VATS thymectomy. ⁽¹⁸⁾

The question of whether extended resection of the thymus and adjacent tissues is the most effective technique is still controversial. Jaretsky compared the results of various series of thymectomies, ranging from those performed with transcervical thymectomy to those carried out using the extended techniques.⁽³¹⁾ The author observed that extended resections reduce the frequency of remissions. The same author reported two problems in the comparison of the various thymectomy techniques. First, median follow up of transcervical thymectomy patients was 8.4 years, whereas it was 3.3 years for extended resection patients. This is significant in light of the well-known fact that the frequency of post-operative remission increases with time. Second, the patients who underwent transcervical thymectomy were, prior to surgery, suffering from milder cases of MG than were those patients who were subjected to more extensive thymectomies.

Mineo et al. reported good results in 96% of patients submitted to thymectomy by left VATS and the post-operative mean classification in those patients was 2.16.⁽¹⁸⁾ The pre-operative mean in our cases was 2.95, showing that most of the myasthenic patients were affected in the muscles with bulbar innervation (Osserman II B). Calhoun et al. presented excellent results using the transcervical technique, with a mean pre-operative classification of 2.7.⁽⁶⁾ However, we were unable to reproduce those results in our study. Another important aspect to be considered is the follow up period. Although the current findings are quite satisfactory, it is possible that outcomes would further improve over a longer follow-up period.

Currently, VATS is a procedure widely used in a variety of situations. Therefore, VATS equipment, which is the same equipment used in laparoscopic surgery, is readily available in many institutions. Thymectomy by VATS employs that same equipment, with the addition of a selective endotracheal tube for single-lung ventilation (average price: US$100). It is therefore possible to perform this procedure in institutions belonging to the Brazilian Sistema Único de Saúde (SUS), or Unified Health System – especially since there is no need for stapling, which would increase the cost.

We conclude that extended thymectomy using bilateral video-assisted thoracoscopy in combination with cervicotomy allowed, in some patients, the resection of ectopic thymic tissue and, in general, offered adequate control of MG. However, in order to evaluate this alternative technique more thoroughly, further studies are warranted. Such studies should involve larger cohorts of patients and longer follow-up periods.

References

Submitted: 25/09/2002. Accepted, after revision: 06/06/2003.

• 1. Higa C, Nunes RA, Saito EH, Guimarães AN. Timectomia "maxima" para miastenia grave. Pulmão (RJ) 1997;6:34-40.
• 2. Henze T, Nenner M, Michaelis HC. Determination of erythrocyte-bound acetylcholinesterase activity for monitoring pyridostigmine therapy in myasthenia gravis. J Neurol 1991;238:225-9.
• 3. Masaoka A, Monden Y, Seike Y, Tanioka T, Kagotani K. Reoperation after transcervical thymectomy for myasthenia gravis. Neurology 1982; 32:83-5.
• 4. Mineo TC, Pompeo E, Ambrogi V, Bernardi G, Iani C, Sabato AF. Video-assisted completion thymectomy in refractory myasthenia gravis. J Thorac Cardiovasc Surg 1998;115:252-4.
• 5. Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty year experience in over 1200 patients. Mt Sinai J Med 1971; 38:497-537.
• 6. Calhoun RF, Ritter JH, Guthrie TJ, Pestronk A, Meyers BF, Patterson GA, et al. Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients. Ann Surg 1999;230:555-61.
• 7. Saito EH, Higa C, Nunes RA, Ribeiro-Netto A, Guimarães AN, Hadad R, et al. Metodização da técnica da timectomia radical por vídeotoracoscopia bilateral associada a cervicotomia transversa na miastenia gravis. Pulmão (RJ) 1998;7:130-40.
• 8. Lanska DJ. Indicatons for thymectomy in myasthenia gravis. Neurology 1990;40:1828-9.
• 9. Shrager JB, Deeb ME, Mick R, Brinster CJ, Chielders HE, Marshall MB, et al. Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy. Ann Thorac Surg 2002;74:320-6.
• 10. Henze A, Biberfeld P, Christensson B, Matell G, Pirskanen R. Failing transcervical thymectomy in myasthenia gravis. Scand J Thorac Cardiovasc Surg 1984;18:235-8.
• 11. Cohn HE, Solit RW, Schartz NJ, Schlezinger N. Surgical treatment in myasthenia gravis. J Thorac Cardiovasc Surg 1974;68:876-81.
• 12. Pêgo-Fernandes PM, Milanez de Campos JR, Jatene FB, Marchiori P, Suso FV, Oliveira SA. Thymectomy by partial sternotomy for the treatment of myasthenia gravis. Ann Thorac Surg 2002;74:204-8.
• 13. Jaretzki III A, Bethea M, Wolff M, Olarte MR, Lovelace RE, Penn AS, et al. A racional approach to total thymectomy in the treatment of myasthenia gravis. Ann Thorac Surg 1977;24:120-30.
• 14. Novelino L, Longoni M, Spinelli L, Andretta M, Cozzi M, Faillace G, et al. "Extended" thymectomy, without sternotomy, performed by cervicotomy and thoracoscopic technique in the treatment of myasthenia gravis. Int Surg 1994;79:378-81.
• 15. Acuff TE. Thoracoscopy for mediastinal masses and thymectomy. In: Brown WT, editor. Atlas of video-assisted thoracic surgery. Philadelphia: W.B. Saunders, 1994;245-9.
• 16. Yim APC, Kay RLC, Ho JKS. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Chest 1995;108:1440-3.
• 17. Kaiser LR. Video-assisted thoracic surgery. Current state of the art. Ann Surg 1994;220:720-34.
• 18. Mineo TC, Pompeo E, Lerut TE, Bernardi G, Coosemans W, Nofroni I. Thoracoscopic thymectomy in autoimmune myasthenia: results of left-sided approach. Ann Thorac Surg 2000;69:1537-41.
• 19. Lennquist S, Andaker Lars, Lindvall B, Smeds S. Combined cervicothoracic approach in thymectomy for myasthenia gravis. Acta Chir Scand 1990;156:53-61.
• 20. Bulkley GB, Bass KN, Stephenson GR, Diener-West M, George S, Reilly PA, et al. Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis. Ann Surg 1997;226:324-35.
• 21. D'Empaire G, Hoaglin DC, Perlo PV, Pontoppidan H. Effect of prethymectomy plasma exchange on postoperative respiratory function in myasthenia gravis. J Thorac Cardiovasc Surg 1985;89:592-6.
• 22. Yusta A, Jiménez MD, Liaño H. Plasmaferésis en el tratamiento de la miastenia gravis. Rev Clin Esp 1986;179:65-8.
• 23. Mulder DS. Pain management principles and anesthesia techniques for thoracoscopy. Ann Thorac Surg 1993;56:630-2.
• 24. Richardson J, Sabanathan S. Pain management in video assisted thoracic surgery: evaluation of localized partial rib resection. A new technique. J Cardiovasc Surg 1995;36:505-9.
• 25. Jaretzki A, Penn AS, Younger DS, Wolf M, Olarte MR, Lovelace RE, et al. "Maximal" thymectomy for myasthenia gravis. Results. J Thorac Cardiovasc Surg 1988;95:747-57.
• 26. Mantegazza R, Confaloniere P, Antozzi C, Novelino L, Ferrò MT, Porta M, et al. Video-assisted thoracoscopic extended thymectomy (VATET) in myasthenia gravis. Two-year follow-up in 101 patients and comparison with the transsternal approach. Ann N Y Acad Sci 1998;841: 749-52.
• 27. Mack MJ, Landreneau RJ, Yim AP, Hazelrigg SR, Scruggs GR. Results of video-assisted thymectomy in patients with myasthenia gravis. J Thorac Cardiovasc Surg 1996;112:1352-60.
• 28. Rückert JC, Walter M, Müller JM. Pulmonary function after thoracoscopic thymectomy versus median sternotomy for myasthenia gravis. Ann Thorac Surg 2000;70:1656-61.
• 29. Ashour M. Prevalence of ectopic thymic tissue in myasthenia gravis and its clinical significance. J Thorac Cardiovasc Surg 1995;109:632-5.
• 30. Scelsi R, Ferrò MT, Scelsi L, Novelino L, Mantegazza R, Cornelio F, et al. Detection and morphology of thymic remnants after video-assisted thoracoscopic extended thymectomy (VATET) in patients with myasthenia gravis. Int Surg 1996;81:14-7.
• 31. Jaretzki A. Outcome after transcervical thymectomy. Ann Thorac Surg 1999;67:592-3.
• 32. Papatestas AE, GenkinsG, Kornfeld P, Eisenkraft JB, Fagerstran RP, Pozner J, et al. Effects of thymectomy in myasthenia gravis. Ann Surg 1987;206:79-88.
• 33. Späth G, Brinkmann A, Huth C, Wietholter H. Complications and efficacy of transsternal thymectomy in myasthenia gravis. Thorac Cardiovasc Surg 1987;35:283-9.

Correspondence to

Hospital Universitário Pedro Ernesto

Av. 28 de Setembro, 77 – 4º andar – Cirurgia Torácica, Vila Isabel

20551-030 – Rio de Janeiro, RJ

Tel.: [phone]

*

Research performed at the Faculdade de Ciências Médicas da Universidade do Rio de Janeiro - UERJ / HUPE

Publication Dates

• Publication in this collection
  02 Mar 2004
• Date of issue
  Oct 2003

History

• Accepted
  12 June 2003
• Received
  25 Sept 2002