Original Article
Thymectomy by video-assisted thoracoscopy versus open surgical techniques
Asian Cardiovascular & Thoracic Annals 2014, Vol. 22(4) 442–447 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492313479596 aan.sagepub.com
Magdi Ibrahim Ahmad Muhammad
Abstract Objective: This study was conducted to compare operative variables and postoperative outcomes in adult patients with myasthenia gravis undergoing thymectomy through 3 different operative techniques: total median sternotomy, partial median sternotomy, and video-assisted thoracoscopy. Methods: 30 patients aged 20–65 years were included in this study. They were subdivided into: group A: 8 patients undergoing thymectomy through a total median sternotomy; group B: 9 patients undergoing thymectomy through a partial median sternotomy; and group C: 13 patients undergoing thymectomy through video-assisted thoracoscopy. Preoperative, intraoperative, and postoperative variables, and mortality were compared among groups. Results: Preoperative variables were well matched in all groups. Operative time was significantly longer in group C. There was no intraoperative complication in any group. Postoperative length of hospital stay was significantly shorter in group C. Postoperative complications occurred in 3 (10%) patients, mostly in groups A and B. There was no perioperative mortality in any group. Conclusions: Video-assisted thymectomy is as effective as the traditional open surgical approaches for thymectomy in the management of patients with myasthenia gravis. In addition, the improved cosmesis of the video-assisted approach ideally should lead to earlier thymectomy in patients with myasthenia gravis.
Keywords Myasthenia gravis, sternotomy, video-assisted thoracoscopy, thymectomy
Introduction Myasthenia gravis is a chronic autoimmune disease resulting from the production of antibodies against postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction. These antibodies are responsible for a reduction in the number of postsynaptic nicotinic acetylcholine receptors, and therefore explain the clinical picture of myasthenia gravis, characterized by progressive weakness and fatigue of the voluntary musculature, which worsens during repetitive exercise and improves with rest. Because fatigue is progressive, it is more intensive at the end of the day. There are no sensitive, reflex, or coordination disturbances in myasthenia gravis.1 The treatment of myasthenia gravis may be medical or surgical. Medical treatment includes the use of anticholinesterase agents, immunotherapy (corticosteroids, azathioprine, immunoglobulins), and
plasmapheresis.2 Surgical thymectomy has been demonstrated to have a positive effect on the course of the disease in most patients. The benefit of thymectomy was first reported by Sauerbruch in 1912 and has been demonstrated repeatedly since the observations of Blalock and colleagues1 in 1939. Surgical approaches include transsternal, transcervical, ‘‘maximal’’ thymectomy, which combines the transsternal and transcervical approaches, partial sternotomy, and most recently, video-assisted thoracoscopy. The thoracoscopic Department of Cardiothoracic Surgery, Faculty of Medicine, Suez Canal University, Egypt; Department of Cardiothoracic Surgery, King Fahd Hospital, Al-Madina Al-Munawara, Saudi Arabia Corresponding author: Magdi Ibrahim Ahmad Muhammad, MD, Department of Thoracic Surgery, King Fahd Hospital, Al-Madina Al-Munawara, Saudi Arabia. Email: [email protected]
Muhammad
443
approach to thymectomy was first reported by Sugarbaker3 from Boston and also a Belgium group in 1993.4 Video-assisted thoracic surgery (VATS) for thymectomy results in less postoperative pain, better preserved pulmonary function, and improved cosmesis, which can be particularly important to many young female myasthenia gravis patients.5 This study was conducted to compare the outcomes of 3 distinctly different operative techniques in the management of myasthenia gravis: thymectomy through a total median sternotomy, a partial median sternotomy, and VATS.
Patients and methods Patient selection This study was carried out at department of thoracic surgery, King Fahd Hospital from January 2008 to December 2010. Thirty patients (9 male and 21 female) were included in this prospective study. The mean age of the patients was 45.8 13.9 years (range, 20–65 years). Inclusion criteria were all adult patients attending our hospital with generalized myasthenic symptoms resistant to medical treatment and refractory symptoms. Exclusion criteria were patients during the initial stage, when spontaneous remission is still possible (usually within the first year of onset) and thymomatous myasthenia gravis. The patients were divided into 3 groups: group A was 8 patients who underwent thymectomy through a total median sternotomy, group B was 9 patients who underwent thymectomy through a
partial median sternotomy, and group C was 13 patients who underwent thymectomy through VATS. Preoperative clinical staging was assessed by the Myasthenia Gravis Foundation of America (MGFA) clinical classification.6 Medication usage and existing comorbidities were also recorded. Follow-up for at least two years was achieved for all patients after discharge from the hospital, by clinical visits as well as telephone contact, and included information as to patient status as assessed by the MGFA postintervention status classification.6 Current medication profiles were also recorded. Institutional review board approval was obtained, and informed consent was obtained from the patients before surgery. Preoperative care: Preoperative preparation depended on the clinical condition of the patient. If there were only motor symptoms with no bulbar impairment, the patient was treated with minimum doses of anticholinesterase drugs, as required for regular activities. Patients with respiratory failure requiring mechanical ventilation were initially treated in the intensive care unit with anticholinesterase drugs, corticosteroids, and immunosuppressors. No patient was ventilatordependent at the time of operation.
Operative Techniques A. Total median sternotomy: Under general anesthesia, the patient was placed in a supine position with a pad under the shoulders. A vertical midline incision was
Table 1. Profile of patients undergoing 3 different operative techniques for thymectomy. Variable
Group A
Group B
Group C
p value
No. of patients Mean age (years) Sex (M/F) MGFA preoperative classification Stage IIa Stage IIIa Operative time (min) Postoperative hospital stay (days) Postoperative complications Pneumothorax Wound infection Hypocalcemia Intercostal neuralgia Phrenic nerve palsy Complete stable remission Clinical improvement Perioperative mortality
8 44.62 13.72 2/6
9 44.11 13.82 2/7
13 45.81 14.82 5/8
0.854
6 2 114.62 11.39 10.12 0.83
4 5 100.66 11.70 8.66 1.00
7 6 164.46 9.87 1.53 0.52
0 2 0 0 0 40% 90% 0
0 1 0 0 0 30% 80% 0
0 0 0 0 0 40% 90% 0
MGFA: Myasthenia Gravis Foundation of America.
0.0001 0.0001
444 made starting 2 cm below the suprasternal notch up to the level of xiphisternum. The incision was carried down through the subcutaneous tissue to expose the upper sternal border, presternal fascia, and the musculature, which were incised down to and through the sternal periosteum. The superior mediastinum above the manubrium was dissected with electrocautery and bluntly with the finger, to clear the posterior wall of the sternum away from the surrounding vascular structures. A full sternotomy was performed using an electrically powered saw. The perithymic fat of the anterior mediastinum was removed en bloc with the gland. The resection margins were the thyroid gland superiorly, the diaphragm inferiorly, and the phrenic nerves laterally. The cervical extensions of the gland were also removed. One large-bore chest tube was placed retrosternally through a separate incision. The sternum was sutured with no. 4 or 5 stainless steel thread, muscular layers were sutured with a 2/0 Vicryl thread, and the subcutaneous and skin layers were sutured to conclude the procedure. B. Partial median sternotomy: The partial median sternotomy was similar to a total median sternotomy but only the manubrium and upper part of the sternal body down to the fourth intercostal space were divided. Subsequently, the upper mediastinum was exposed by a Finochietto retractor with lateral and progressive retraction. The thymus was exposed and totally removed, including its surrounding fat, starting superiorly from the base of the thyroid gland using the phrenic nerves as lateral limits, and proceeding inferiorly until the pericardium. During dissection, the mediastinal pleura should be pushed laterally, to avoid inadvertently rupturing the pleura. If this should happen, it must be sutured immediately. Also, the phrenic nerves should be identified and excessive manipulation and lesions must be avoided to prevent postoperative diaphragmatic palsy, which could seriously impair the clinical outcome of the patient. After resection, the thymic bed was carefully assessed to assure a radical thymectomy, adequate hemostasis, and intact pleural spaces. A Porto-Vac suction catheter was routinely placed close to the sternal notch. The sternum was sutured with no. 4 or 5 stainless steel thread, muscular layers were sutured with 2/0 Vicryl thread, and the subcutaneous and skin layers were sutured to conclude the procedure. C. Video-assisted thoracoscopy: The 3-port VATS procedure was conducted under general anesthesia, using a double-lumen endotracheal tube for selective one-lung ventilation, and a right-sided approach with the patient placed at a 30-degree angle from the horizontal by a roll placed under the back on the right side. The thoracoscope port incision was in front of the tip of the scapula
Asian Cardiovascular & Thoracic Annals 22(4) along the posterior axillary line for insertion of the 10mm port and 0-degree telescope. The 2nd and 3rd 5mm instrument ports were inserted by an open technique under direct thoracoscopic vision at the 3rd intercostal space on the midaxillary line and the 6th intercostal space on the anterior axillary line. In young females, the ports can be placed over the submammary fold for cosmetic considerations. With the use of standard endoscopic instruments including a tissue-grasping forceps and endoscopic scissors, the dissection was begun at the inferior portion of the thymic gland just anterior to the phrenic nerve. By a combination of sharp and blunt dissection, all anterior mediastinal tissue was teased off the pericardium. The mediastinal pleura was divided in the retrosternal area, and the anterior portion of the thymic gland was dissected from the retrosternal area. The arterial blood supply to the thymic gland that arises from the internal thoracic artery was ligated with endoscopic clips. At this point, the innominate vein can be identified. Dissection was carried carefully along the innominate vein until the thymic branches entering the innominate vein were identified and divided with an endoscopic clip. Next, the gland was dissected off the contralateral pleura by blunt dissection, avoiding injury to the contralateral phrenic nerve. Once the gland was mobilized to this point, it was often helpful to introduce a fan retractor or other instrument to retract the bulk of thymic tissue out of the way so that dissection into the cervical area could continue. Finally, dissection was carried cephalad to the innominate vein until the superior horns of the thymic gland were identified. The fascial attachments of the thymic gland to the inferior portion of the thyroid gland were divided. The brachiocephalic veins were skeletonized and the junction to form the superior vena cava clearly visualized. When dissection of the thymic gland was complete, including the cervical area, the tissue was removed through an anterior trocar site in a specimen bag, which allows easier extraction without fragmentation and also avoids potential seeding of the chest wall if a thymoma is present in the specimen. Hemostasis was obtained, and the lung was reinflated. A chest tube or drain was not routinely used. The incisions were closed with a subcuticular suture.
Postoperative care The postoperative protocol consisted of early extubation in the operating room, 50% reduction in the administration of anticholinesterase drugs, maintenance of the same dose of corticosteroid to the 3rd postoperative week, and then gradual tapering. Immunosuppressive therapy with cytotoxic drugs and plasmapheresis was only used in patients with persistent
Muhammad symptoms or resistance to corticosteroids. A postoperative sitting chest radiograph was taken, and chest physiotherapy was encouraged with adequate pain control. The mediastinal drain was removed on the first postoperative day after confirming no air leak or bleeding.
Data analysis All data were collected including preoperative demographic details. The effects of the 3 different operative techniques were evaluated on the following clinical outcomes: operative time which was defined as the interval between surgical skin incision or first port incision and completion of wound closure; intraoperative complications; postoperative complications including pneumothorax, hypocalcemia, wound infection, intercostal neuralgia, and phrenic nerve palsy; postoperative length of hospital stay which was defined as the interval between the date of intervention and the date of hospital discharge; MGFA postintervention status classification; and perioperative mortality rate which was defined as the percentage of patients who died of causes related or unrelated to the disease or procedure within 30 days of surgery.
Statistical analysis The data are expressed as mean standard deviation and percentage. Significance of measured changes were assessed using an independent t test, while oneway analysis of variance was used within and between groups. A p value < 0.05 was considered statistically significant. Data were analyzed using SPSS version 13.0 for Windows (SPSS Inc, Chicago, IL, USA).
Results Thirty patients (9 males and 21 females) with mean age of 45.8 13.9 years (20–65 years) were operated upon in our department. In all groups, preoperative variables were well matched for age, sex and preoperative clinical staging according to the MGFA clinical classification (Table 1). Operative time was significantly longer (p ¼ 0.0001) in group C (Table 1). There were no intraoperative complications, and no patient required a blood transfusion. Postoperative hospital stay was significantly shorter in group C. Postoperative complications occurred in 3 (10%) patients in the form of superficial wound infection (2 in group A, 1 in group B) that were treated effectively with proper antibiotics after culture and sensitivity. There was no phrenic nerve injury and no injury of the internal thoracic arteries. There was no residual pneumothorax or hemothorax, and no diaphragmatic palsy was
445 detected by chest radiography. Pain control was adequate with nonsteroidal analgesics. A full sternotomy to complete the operation was not needed in groups B or C in our series, and none of our patients required reoperation. There was no intraoperative or postoperative mortality. In groups A and C, the complete stable remission rate was 40%, while in group B, it was 30%. Clinical improvement according to the MGFA postintervention status classification was 90% in patients who underwent VATS thymectomy and total median sternotomy while patients who underwent a partial median sternotomy showed 80% clinical improvement.
Discussion Surgical management of myasthenia gravis has been recognized as an effective treatment option for this autoimmune disorder of neuromuscular transmission. The best surgical approach to thymectomy remains controversial. Regardless of technique, it is generally agreed that the ultimate surgical goal of thymectomy is to completely remove the gland and the anterior mediastinal tissue. One of several controversies regarding the role of thymectomy in myasthenia gravis management has revolved around which operative procedure produces an adequate thymectomy while minimizing adverse outcomes and facilitating patient recovery from the procedure. Options have included total median sternotomy, partial median sternotomy, the transcervical approach, the combined transcervical-transsternal maximum thymectomy, and most recently, VATS thymectomy.7 Regarding VATS thymectomy, there is controversy over the exact technique and in particular, whether the thymus should be approached from the left or right. Mineo and colleagues8 advocated a left-sided approach and the use of pneumomediastinum to facilitate dissection. They believe the dissection maneuvers are safer from the left because the superior vena cava lies out of the surgical field, thus reducing the risk of accidental injury. In addition, removal of the perithymic fatty tissue around the left pericardiophrenic angle and aortopulmonary window can be performed more readily from the left. On the other hand, we and several other centers advocate a right-sided approach for the following reasons.5,7,9 First, there is more room in the right thoracic cavity, allowing greater maneuverability of telescope and instrumentation. Second, the presence of the superior vena cava as an early landmark allows easier definition of the vascular structures and identification of the innominate vein during the course of the dissection. Finally, the recess at the junction between the superior vena cava and innominate vein is better visualized and defined from the right side. On the left
446 side, this junction is the most difficult area in which to perform the dissection, whereas an approach through the right side aids dissection in this area. Tomulescu and colleagues10 found no difference in clinical outcomes between patients undergoing left or right VATS thymectomy for non-thymomatous myasthenia gravis. Ru¨ckert and colleagues11 carried out a comparative study of pulmonary function after thymectomy through VATS and total median sternotomy approaches and reported that pulmonary function was significantly better preserved in the immediate postoperative period, followed by a faster recovery after VATS thymectomy compared to a total median sternotomy approach. Such an advantage may contribute toward earlier extubation and potential reduction in the incidence of postoperative pulmonary infection. In a study by Grandjean and colleagues,12 pleural complications were reported in 6% of the patients. They also reported 3 cases of wound infection, and the pectoral muscle had to be used in one of them to repair sternal leakage. So there is a great advantage of partial sternotomy over total sternotomy, as the possibilities of wound infection, mediastinitis, and sternal destabilization are much lower. In this study, superficial wound infection occurred in 3 (10%) patients who were treated effectively with proper antibiotics after culture and sensitivity tests. The patient groups were assessed by the MGFA preoperative classification, and postintervention status was analyzed using MGFA guidelines. Analysis of the groups showed highly significant differences in operative time and postoperative hospital stay; group C had a longer operative time and shorter postoperative hospital stay. The long duration of the procedure in group C patients was due to the need for meticulous dissection to remove all thymic tissues in the narrow space surrounded by great vessels. Also, patients who underwent thoracoscopic thymectomy had significantly lower analgesic requirements. These findings are supported by other studies.7,13 The most radical surgical approach does not result in a remission rate >40%. Furthermore, the majority of ectopic thymus tissue is actually microscopic and may even be missed by radical thymectomy.14 The results in this study are very similar to other series that reported remission rates of 10%–40%.14–16 In groups A and C, the complete stable remission rate was 40%, while it was 30% in group B. Clinical improvement was observed in 90% of patients who underwent thoracoscopic thymectomy and total median sternotomy, while those who underwent a partial median sternotomy demonstrated 80% clinical improvement. Similar results were reported by other groups.17,18 It was concluded that VATS thymectomy is as effective as the traditional open surgical approaches for
Asian Cardiovascular & Thoracic Annals 22(4) thymectomy in the management of patients with myasthenia gravis. In addition, the improved cosmesis of the VATS approach should lead to earlier thymectomy in patients with myasthenia gravis. Accepted to be presented at the 33rd Annual Cardiothoracic Surgery Symposium (CREF 2013), San Diego, USA, February 6–9, 2013; the Society for Cardiothoracic Surgery in Great Britain & Ireland Annual Meeting and Cardiothoracic Forum, Brighton, UK, March 17–19, 2013; the 9th International Congress of Update in Cardiology and Cardiovascular Surgery (UCCVS), Antalya, Turkey, March 21–24, 2013; the 21st Annual Meeting of the Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS2013), Kobe, Japan, April 4–7, 2013; the Annual Scientific Meeting of International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS), Prague, Czech Republic, June 12–15, 2013 and European Multidisciplinary Conference in Thoracic Oncology (EMCTO 2013), Lugano, Switzerland, May 9–11, 2013. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
References 1. Peˆgo-Fernandes PM, de Campos JR, Jatene FB, Marchiori P, Suso FV and de Oliveira SA. Thymectomy by partial sternotomy for the treatment of myasthenia gravis. Ann Thorac Surg 2002; 74: 204–208. 2. Papatestas AE, Genkins G, Kornfeld P, et al. Effects of thymectomy in myasthenia gravis. Ann Surg 1987; 206: 79–88. 3. Sugarbaker DJ. Thoracoscopy in the management of anterior mediastinal masses. Ann Thorac Surg 1993; 56: 653–656. 4. Coosemans W, Lerut TE and Van Raemdonck DE. Thoracoscopic surgery: the Belgian experience. Ann Thorac Surg 1993; 56: 721–730. 5. Ng CS, Wan IY and Yim AP. Video-assisted thoracic surgery thymectomy: the better approach. Ann Thorac Surg 2010; 89: S2135–S2141. 6. Jaretzki A, Barohn R and Ernstoff RM. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Ann Thorac Surg 2000; 70: 327–334. 7. Meyer DM, Herbert MA, Sobhani NC, et al. Comparative clinical outcomes of thymectomy for myasthenia gravis performed by extended transsternal and minimally invasive approaches. Ann Thorac Surg 2009; 87: 385–391.
Muhammad 8. Mineo TC, Pompeo E, Lerut TE, Bernardi G, Coosemans W and Nofroni I. Thoracoscopic thymectomy in autoimmune myasthenia gravis: results of left-sided approach. Ann Thorac Surg 2000; 69: 1537–1541. 9. Yim AP. Thoracoscopic thymectomy: which side to approach [Letter]? Ann Thorac Surg 1997; 64: 584–585. 10. Tomulescu V, Ion V, Kosa A, Sgarbura O and Popescu I. Thoracoscopic thymectomy mid-term results. Ann Thorac Surg 2006; 82: 1003–1007. 11. Ru¨ckert JC, Walter M and Mu¨ller JM. Pulmonary function after thoracoscopic thymectomy versus median sternotomy for myasthenia gravis. Ann Thorac Surg 2000; 70: 1656–1661. 12. Grandjean JG, Lucchi M and Mariani MA. Reversed-T upper mini-sternotomy for extended thymectomy in myasthenic patients. Ann Thorac Surg 2000; 70: 1423–1424. 13. Mack MJ, Landreneau RJ, Yim AP, Hazelrigg SR and Scruggs GR. Results of video-assisted thymectomy in
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patients with myasthenia gravis. J Thorac Cardiovasc Surg 1996; 112: 1352–1360. Pompeo E, Nofroni I, Iavicoli N and Mineo TC. Thoracoscopic completion thymectomy in refractory nonthymomatous myasthenia. Ann Thorac Surg 2000; 70: 918–923. Bril V, Kojic J, Ilse WK and Cooper JD. Long-term clinical outcome after transcervical thymectomy for myasthenia gravis. Ann Thorac Surg 1998; 65: 1520–1522. Kattach H, Anastasiadis K, Cleuziou J, et al. Transsternal thymectomy for myasthenia gravis: surgical outcome. Ann Thorac Surg 2006; 81: 305–308. Savcenko M, Wendt GK, Prince SL and Mack MJ. Video-assisted thymectomy for myasthenia gravis: an update of a single institution experience. Eur J Cardiothorac Surg 2002; 22: 978–983. Manlulu A, Lee TW, Wan I, et al. Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis. Chest 2005; 128: 3454–3460.
Thymectomy by video-assisted thoracoscopy versus open surgical techniques
Asian Cardiovascular & Thoracic Annals 2014, Vol. 22(4) 442–447 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492313479596 aan.sagepub.com
Magdi Ibrahim Ahmad Muhammad
Abstract Objective: This study was conducted to compare operative variables and postoperative outcomes in adult patients with myasthenia gravis undergoing thymectomy through 3 different operative techniques: total median sternotomy, partial median sternotomy, and video-assisted thoracoscopy. Methods: 30 patients aged 20–65 years were included in this study. They were subdivided into: group A: 8 patients undergoing thymectomy through a total median sternotomy; group B: 9 patients undergoing thymectomy through a partial median sternotomy; and group C: 13 patients undergoing thymectomy through video-assisted thoracoscopy. Preoperative, intraoperative, and postoperative variables, and mortality were compared among groups. Results: Preoperative variables were well matched in all groups. Operative time was significantly longer in group C. There was no intraoperative complication in any group. Postoperative length of hospital stay was significantly shorter in group C. Postoperative complications occurred in 3 (10%) patients, mostly in groups A and B. There was no perioperative mortality in any group. Conclusions: Video-assisted thymectomy is as effective as the traditional open surgical approaches for thymectomy in the management of patients with myasthenia gravis. In addition, the improved cosmesis of the video-assisted approach ideally should lead to earlier thymectomy in patients with myasthenia gravis.
Keywords Myasthenia gravis, sternotomy, video-assisted thoracoscopy, thymectomy
Introduction Myasthenia gravis is a chronic autoimmune disease resulting from the production of antibodies against postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction. These antibodies are responsible for a reduction in the number of postsynaptic nicotinic acetylcholine receptors, and therefore explain the clinical picture of myasthenia gravis, characterized by progressive weakness and fatigue of the voluntary musculature, which worsens during repetitive exercise and improves with rest. Because fatigue is progressive, it is more intensive at the end of the day. There are no sensitive, reflex, or coordination disturbances in myasthenia gravis.1 The treatment of myasthenia gravis may be medical or surgical. Medical treatment includes the use of anticholinesterase agents, immunotherapy (corticosteroids, azathioprine, immunoglobulins), and
plasmapheresis.2 Surgical thymectomy has been demonstrated to have a positive effect on the course of the disease in most patients. The benefit of thymectomy was first reported by Sauerbruch in 1912 and has been demonstrated repeatedly since the observations of Blalock and colleagues1 in 1939. Surgical approaches include transsternal, transcervical, ‘‘maximal’’ thymectomy, which combines the transsternal and transcervical approaches, partial sternotomy, and most recently, video-assisted thoracoscopy. The thoracoscopic Department of Cardiothoracic Surgery, Faculty of Medicine, Suez Canal University, Egypt; Department of Cardiothoracic Surgery, King Fahd Hospital, Al-Madina Al-Munawara, Saudi Arabia Corresponding author: Magdi Ibrahim Ahmad Muhammad, MD, Department of Thoracic Surgery, King Fahd Hospital, Al-Madina Al-Munawara, Saudi Arabia. Email: [email protected]
Muhammad
443
approach to thymectomy was first reported by Sugarbaker3 from Boston and also a Belgium group in 1993.4 Video-assisted thoracic surgery (VATS) for thymectomy results in less postoperative pain, better preserved pulmonary function, and improved cosmesis, which can be particularly important to many young female myasthenia gravis patients.5 This study was conducted to compare the outcomes of 3 distinctly different operative techniques in the management of myasthenia gravis: thymectomy through a total median sternotomy, a partial median sternotomy, and VATS.
Patients and methods Patient selection This study was carried out at department of thoracic surgery, King Fahd Hospital from January 2008 to December 2010. Thirty patients (9 male and 21 female) were included in this prospective study. The mean age of the patients was 45.8 13.9 years (range, 20–65 years). Inclusion criteria were all adult patients attending our hospital with generalized myasthenic symptoms resistant to medical treatment and refractory symptoms. Exclusion criteria were patients during the initial stage, when spontaneous remission is still possible (usually within the first year of onset) and thymomatous myasthenia gravis. The patients were divided into 3 groups: group A was 8 patients who underwent thymectomy through a total median sternotomy, group B was 9 patients who underwent thymectomy through a
partial median sternotomy, and group C was 13 patients who underwent thymectomy through VATS. Preoperative clinical staging was assessed by the Myasthenia Gravis Foundation of America (MGFA) clinical classification.6 Medication usage and existing comorbidities were also recorded. Follow-up for at least two years was achieved for all patients after discharge from the hospital, by clinical visits as well as telephone contact, and included information as to patient status as assessed by the MGFA postintervention status classification.6 Current medication profiles were also recorded. Institutional review board approval was obtained, and informed consent was obtained from the patients before surgery. Preoperative care: Preoperative preparation depended on the clinical condition of the patient. If there were only motor symptoms with no bulbar impairment, the patient was treated with minimum doses of anticholinesterase drugs, as required for regular activities. Patients with respiratory failure requiring mechanical ventilation were initially treated in the intensive care unit with anticholinesterase drugs, corticosteroids, and immunosuppressors. No patient was ventilatordependent at the time of operation.
Operative Techniques A. Total median sternotomy: Under general anesthesia, the patient was placed in a supine position with a pad under the shoulders. A vertical midline incision was
Table 1. Profile of patients undergoing 3 different operative techniques for thymectomy. Variable
Group A
Group B
Group C
p value
No. of patients Mean age (years) Sex (M/F) MGFA preoperative classification Stage IIa Stage IIIa Operative time (min) Postoperative hospital stay (days) Postoperative complications Pneumothorax Wound infection Hypocalcemia Intercostal neuralgia Phrenic nerve palsy Complete stable remission Clinical improvement Perioperative mortality
8 44.62 13.72 2/6
9 44.11 13.82 2/7
13 45.81 14.82 5/8
0.854
6 2 114.62 11.39 10.12 0.83
4 5 100.66 11.70 8.66 1.00
7 6 164.46 9.87 1.53 0.52
0 2 0 0 0 40% 90% 0
0 1 0 0 0 30% 80% 0
0 0 0 0 0 40% 90% 0
MGFA: Myasthenia Gravis Foundation of America.
0.0001 0.0001
444 made starting 2 cm below the suprasternal notch up to the level of xiphisternum. The incision was carried down through the subcutaneous tissue to expose the upper sternal border, presternal fascia, and the musculature, which were incised down to and through the sternal periosteum. The superior mediastinum above the manubrium was dissected with electrocautery and bluntly with the finger, to clear the posterior wall of the sternum away from the surrounding vascular structures. A full sternotomy was performed using an electrically powered saw. The perithymic fat of the anterior mediastinum was removed en bloc with the gland. The resection margins were the thyroid gland superiorly, the diaphragm inferiorly, and the phrenic nerves laterally. The cervical extensions of the gland were also removed. One large-bore chest tube was placed retrosternally through a separate incision. The sternum was sutured with no. 4 or 5 stainless steel thread, muscular layers were sutured with a 2/0 Vicryl thread, and the subcutaneous and skin layers were sutured to conclude the procedure. B. Partial median sternotomy: The partial median sternotomy was similar to a total median sternotomy but only the manubrium and upper part of the sternal body down to the fourth intercostal space were divided. Subsequently, the upper mediastinum was exposed by a Finochietto retractor with lateral and progressive retraction. The thymus was exposed and totally removed, including its surrounding fat, starting superiorly from the base of the thyroid gland using the phrenic nerves as lateral limits, and proceeding inferiorly until the pericardium. During dissection, the mediastinal pleura should be pushed laterally, to avoid inadvertently rupturing the pleura. If this should happen, it must be sutured immediately. Also, the phrenic nerves should be identified and excessive manipulation and lesions must be avoided to prevent postoperative diaphragmatic palsy, which could seriously impair the clinical outcome of the patient. After resection, the thymic bed was carefully assessed to assure a radical thymectomy, adequate hemostasis, and intact pleural spaces. A Porto-Vac suction catheter was routinely placed close to the sternal notch. The sternum was sutured with no. 4 or 5 stainless steel thread, muscular layers were sutured with 2/0 Vicryl thread, and the subcutaneous and skin layers were sutured to conclude the procedure. C. Video-assisted thoracoscopy: The 3-port VATS procedure was conducted under general anesthesia, using a double-lumen endotracheal tube for selective one-lung ventilation, and a right-sided approach with the patient placed at a 30-degree angle from the horizontal by a roll placed under the back on the right side. The thoracoscope port incision was in front of the tip of the scapula
Asian Cardiovascular & Thoracic Annals 22(4) along the posterior axillary line for insertion of the 10mm port and 0-degree telescope. The 2nd and 3rd 5mm instrument ports were inserted by an open technique under direct thoracoscopic vision at the 3rd intercostal space on the midaxillary line and the 6th intercostal space on the anterior axillary line. In young females, the ports can be placed over the submammary fold for cosmetic considerations. With the use of standard endoscopic instruments including a tissue-grasping forceps and endoscopic scissors, the dissection was begun at the inferior portion of the thymic gland just anterior to the phrenic nerve. By a combination of sharp and blunt dissection, all anterior mediastinal tissue was teased off the pericardium. The mediastinal pleura was divided in the retrosternal area, and the anterior portion of the thymic gland was dissected from the retrosternal area. The arterial blood supply to the thymic gland that arises from the internal thoracic artery was ligated with endoscopic clips. At this point, the innominate vein can be identified. Dissection was carried carefully along the innominate vein until the thymic branches entering the innominate vein were identified and divided with an endoscopic clip. Next, the gland was dissected off the contralateral pleura by blunt dissection, avoiding injury to the contralateral phrenic nerve. Once the gland was mobilized to this point, it was often helpful to introduce a fan retractor or other instrument to retract the bulk of thymic tissue out of the way so that dissection into the cervical area could continue. Finally, dissection was carried cephalad to the innominate vein until the superior horns of the thymic gland were identified. The fascial attachments of the thymic gland to the inferior portion of the thyroid gland were divided. The brachiocephalic veins were skeletonized and the junction to form the superior vena cava clearly visualized. When dissection of the thymic gland was complete, including the cervical area, the tissue was removed through an anterior trocar site in a specimen bag, which allows easier extraction without fragmentation and also avoids potential seeding of the chest wall if a thymoma is present in the specimen. Hemostasis was obtained, and the lung was reinflated. A chest tube or drain was not routinely used. The incisions were closed with a subcuticular suture.
Postoperative care The postoperative protocol consisted of early extubation in the operating room, 50% reduction in the administration of anticholinesterase drugs, maintenance of the same dose of corticosteroid to the 3rd postoperative week, and then gradual tapering. Immunosuppressive therapy with cytotoxic drugs and plasmapheresis was only used in patients with persistent
Muhammad symptoms or resistance to corticosteroids. A postoperative sitting chest radiograph was taken, and chest physiotherapy was encouraged with adequate pain control. The mediastinal drain was removed on the first postoperative day after confirming no air leak or bleeding.
Data analysis All data were collected including preoperative demographic details. The effects of the 3 different operative techniques were evaluated on the following clinical outcomes: operative time which was defined as the interval between surgical skin incision or first port incision and completion of wound closure; intraoperative complications; postoperative complications including pneumothorax, hypocalcemia, wound infection, intercostal neuralgia, and phrenic nerve palsy; postoperative length of hospital stay which was defined as the interval between the date of intervention and the date of hospital discharge; MGFA postintervention status classification; and perioperative mortality rate which was defined as the percentage of patients who died of causes related or unrelated to the disease or procedure within 30 days of surgery.
Statistical analysis The data are expressed as mean standard deviation and percentage. Significance of measured changes were assessed using an independent t test, while oneway analysis of variance was used within and between groups. A p value < 0.05 was considered statistically significant. Data were analyzed using SPSS version 13.0 for Windows (SPSS Inc, Chicago, IL, USA).
Results Thirty patients (9 males and 21 females) with mean age of 45.8 13.9 years (20–65 years) were operated upon in our department. In all groups, preoperative variables were well matched for age, sex and preoperative clinical staging according to the MGFA clinical classification (Table 1). Operative time was significantly longer (p ¼ 0.0001) in group C (Table 1). There were no intraoperative complications, and no patient required a blood transfusion. Postoperative hospital stay was significantly shorter in group C. Postoperative complications occurred in 3 (10%) patients in the form of superficial wound infection (2 in group A, 1 in group B) that were treated effectively with proper antibiotics after culture and sensitivity. There was no phrenic nerve injury and no injury of the internal thoracic arteries. There was no residual pneumothorax or hemothorax, and no diaphragmatic palsy was
445 detected by chest radiography. Pain control was adequate with nonsteroidal analgesics. A full sternotomy to complete the operation was not needed in groups B or C in our series, and none of our patients required reoperation. There was no intraoperative or postoperative mortality. In groups A and C, the complete stable remission rate was 40%, while in group B, it was 30%. Clinical improvement according to the MGFA postintervention status classification was 90% in patients who underwent VATS thymectomy and total median sternotomy while patients who underwent a partial median sternotomy showed 80% clinical improvement.
Discussion Surgical management of myasthenia gravis has been recognized as an effective treatment option for this autoimmune disorder of neuromuscular transmission. The best surgical approach to thymectomy remains controversial. Regardless of technique, it is generally agreed that the ultimate surgical goal of thymectomy is to completely remove the gland and the anterior mediastinal tissue. One of several controversies regarding the role of thymectomy in myasthenia gravis management has revolved around which operative procedure produces an adequate thymectomy while minimizing adverse outcomes and facilitating patient recovery from the procedure. Options have included total median sternotomy, partial median sternotomy, the transcervical approach, the combined transcervical-transsternal maximum thymectomy, and most recently, VATS thymectomy.7 Regarding VATS thymectomy, there is controversy over the exact technique and in particular, whether the thymus should be approached from the left or right. Mineo and colleagues8 advocated a left-sided approach and the use of pneumomediastinum to facilitate dissection. They believe the dissection maneuvers are safer from the left because the superior vena cava lies out of the surgical field, thus reducing the risk of accidental injury. In addition, removal of the perithymic fatty tissue around the left pericardiophrenic angle and aortopulmonary window can be performed more readily from the left. On the other hand, we and several other centers advocate a right-sided approach for the following reasons.5,7,9 First, there is more room in the right thoracic cavity, allowing greater maneuverability of telescope and instrumentation. Second, the presence of the superior vena cava as an early landmark allows easier definition of the vascular structures and identification of the innominate vein during the course of the dissection. Finally, the recess at the junction between the superior vena cava and innominate vein is better visualized and defined from the right side. On the left
446 side, this junction is the most difficult area in which to perform the dissection, whereas an approach through the right side aids dissection in this area. Tomulescu and colleagues10 found no difference in clinical outcomes between patients undergoing left or right VATS thymectomy for non-thymomatous myasthenia gravis. Ru¨ckert and colleagues11 carried out a comparative study of pulmonary function after thymectomy through VATS and total median sternotomy approaches and reported that pulmonary function was significantly better preserved in the immediate postoperative period, followed by a faster recovery after VATS thymectomy compared to a total median sternotomy approach. Such an advantage may contribute toward earlier extubation and potential reduction in the incidence of postoperative pulmonary infection. In a study by Grandjean and colleagues,12 pleural complications were reported in 6% of the patients. They also reported 3 cases of wound infection, and the pectoral muscle had to be used in one of them to repair sternal leakage. So there is a great advantage of partial sternotomy over total sternotomy, as the possibilities of wound infection, mediastinitis, and sternal destabilization are much lower. In this study, superficial wound infection occurred in 3 (10%) patients who were treated effectively with proper antibiotics after culture and sensitivity tests. The patient groups were assessed by the MGFA preoperative classification, and postintervention status was analyzed using MGFA guidelines. Analysis of the groups showed highly significant differences in operative time and postoperative hospital stay; group C had a longer operative time and shorter postoperative hospital stay. The long duration of the procedure in group C patients was due to the need for meticulous dissection to remove all thymic tissues in the narrow space surrounded by great vessels. Also, patients who underwent thoracoscopic thymectomy had significantly lower analgesic requirements. These findings are supported by other studies.7,13 The most radical surgical approach does not result in a remission rate >40%. Furthermore, the majority of ectopic thymus tissue is actually microscopic and may even be missed by radical thymectomy.14 The results in this study are very similar to other series that reported remission rates of 10%–40%.14–16 In groups A and C, the complete stable remission rate was 40%, while it was 30% in group B. Clinical improvement was observed in 90% of patients who underwent thoracoscopic thymectomy and total median sternotomy, while those who underwent a partial median sternotomy demonstrated 80% clinical improvement. Similar results were reported by other groups.17,18 It was concluded that VATS thymectomy is as effective as the traditional open surgical approaches for
Asian Cardiovascular & Thoracic Annals 22(4) thymectomy in the management of patients with myasthenia gravis. In addition, the improved cosmesis of the VATS approach should lead to earlier thymectomy in patients with myasthenia gravis. Accepted to be presented at the 33rd Annual Cardiothoracic Surgery Symposium (CREF 2013), San Diego, USA, February 6–9, 2013; the Society for Cardiothoracic Surgery in Great Britain & Ireland Annual Meeting and Cardiothoracic Forum, Brighton, UK, March 17–19, 2013; the 9th International Congress of Update in Cardiology and Cardiovascular Surgery (UCCVS), Antalya, Turkey, March 21–24, 2013; the 21st Annual Meeting of the Asian Society for Cardiovascular and Thoracic Surgery (ASCVTS2013), Kobe, Japan, April 4–7, 2013; the Annual Scientific Meeting of International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS), Prague, Czech Republic, June 12–15, 2013 and European Multidisciplinary Conference in Thoracic Oncology (EMCTO 2013), Lugano, Switzerland, May 9–11, 2013. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
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