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Minimally invasive approach for tumoral and non tumoral myasthenia gravis; from thoracoscopic to robotic surgery

Minimally invasive approach for tumoral and non tumoral myasthenia gravis; from thoracoscopic to... The purpose of this study is to evaluate whether a thoracoscopic resection assisted or not by the computer can be successfully performed to treat nontumoral myasthenia gravis and early-stage tumors of the anterior mediastinum with results as good as in open approach. There have been 358 patients with tumoral (TMG) and nontumoral myasthenia gravis (NTMG) that have suffered an extended thoracoscopic thymectomy in our center between April 1999 and April 2010. 319 patients have been operated using a classic thoracoscopic approach and 39 using a robotic approach. The study population consisted in 72 male patients (20.2%) and 286 female patients (79.8%), aged 8­70 years. For NTMG we do not operate pactients over 60 years of age. The indication for surgery have been in 34 cases thymic tumors ­ thymoma, and in 324 cases NTMG. The following histological diagnoses (fig 12) were made for NTMG: normal thymus in 20 cases, involuted thymus in 88 cases and thymus hypertrophy (hyperplastic thymus) in 216 cases. The pathological results for TMG have been cortical thymoma in 16 patients, mixed thymoma in 8 patients, medular thymoma in 6 patients and well differentiated thymic carcinoma (WDTC) in 2 patients. Postoperative treatment only for stage III Masaoka without any sign of recurrence during the follow-up period of 3 to 92 months. The mean duration of hospitalization was 3.6 days (range 2-18 days). All thymoma patients survived without any sign of recurrence during the follow-up period of 3 to 92 months. In conclusion we consider that the thoracoscopic surgery, classic or robotic assisted for nontumoral and tumoral myasthenia gravis is no doubt beneficially in selected cases in relation to no mortality, low morbidity and good oncology outcome. Key words: myasthenia gravis, thymoma, thoracoscopic surgery, robotic surgery Introduction The standard surgical procedure for the treatment of anterior mediastinal masses has been the transsternal approach. Some reports have shown that thoracoscopic resection of the anterior mediastinal masses is technically feasible in selected patients (1). In 1992, Landrenau et al.(2) and Lewis et al.(3) and in 1993, Hazelrigg et al.(4), and Naunheim and Andrus(5) reported their experience using the miniinvasive approach (video-assisted thoracoscopic surgery) on some mediastinal lesions. Minimally invasive techniques have become increasingly popular due to their low procedural morbidity and mortality, improved cosmesis, Address for correspondence: Victor Tomulescu, MD, "Dan Setlacec" Center for General Surgery and Liver Transplantation, Fundeni Clinical Institute, Sos. Fundeni, 258, 022328, Bucharest, Romania, e-mail: victor.tomulescu@gmail.com lesser degree of access trauma, and equivalent efficacy compared to conventional open techniques. In 2001, Yoshino described the first robotic thymectomy in the treatment of small thymoma. In 2003, Ashton and Rea published a case report on robotic thymectomy in MG using two different approaches: the first adopted a right-sided approach with completion of the operation through a left-sided approach, the second used a leftsided approach only(6;7). Materials and methods We have started the thoracoscopic approach for anterior mediastinal lesions in 1999. At the beginning we have performed only thoracoscopic thymectomy for nontumoral myasthenia gravis and then, with growing experience to other lesions of anterior mediastinum(8;9). Since April 1999, a thoracoscopic approach has been used in all patients admitted in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute with either nontumoral myasthenia gravis (NTMG) or stage I and IIa Masaoka thymomas (TMG). We have start the robotic approach in 2008 and robotic approach of anterior mediastinum have become one of the priorities of our department. There have been 358 patients with tumoral and nontumoral myasthenia gravis (NTMG) that have suffered an extended thoracoscopic thymectomy in our center between April 1999 and April 2010. 319 patients have been operated using a classic thoracoscopic approach and 39 using a robotic approach The purpose of this study is to evaluate whether a thoracoscopic resection assisted or not by the computer can be successfully performed to treat nontumoral myasthenia gravis and earlystage tumors of the anterior mediastinum with results as good as in open approach Informed consent was obtained from all patients. The patients were informed about the disease, different treatment options, surgical approaches and potential benefits and complications. Our study was approved by the Fundeni Clinical Institute Ethics Committee in accordance with the ethical standards of the Helsinki Declaration of 1975. The diagnose of MG were based on patient's histories, physical examinations, positive responses to anticholinesterase agents and electrophysiology studies. Preoperative diagnostic tests included spirometry and a computed tomography (CT) scan. For thymomas CT image considerations included the location of the tumor in the anterior mediastinum, a distinct fat plane between the tumor and vital organ, unilateral tumor predominance, tumor encapsulation, existence of residual normalappearing thymic tissue, and no mass compression effect. The enrollees were expected to be free of pleural effusion, pericardial effusion, paralysis of hemidiaphragm, and the encasement of great vessels We considered that favourable outcomes requires highly coordinated teamwork involving a strong collaboration between neurologists, surgeons, and anesthesiologists in making appropriate decisions on selection of patients, therapeutic options, and timing of surgery. All of the patients received specific treatment for at least 3 months before surgery in the Department of Neurology of our institute. Patients were considered suitable for a surgical procedure only when evidence showed good treatment tolerance and a stable quantitative myasthenia gravis (QMG) score of at least 10 points. For NTMG we did not operate patients with pure ocular myasthenia gravis because we considered that the indication for thymectomy in ocular myasthenia gravis remained controversial. Surgical technique Thoracoscopic technique The procedure is a thoracoscopic unilaterally extended thymectomy that routinely removed the entire gland and all anterior mediastinal perithymic fatty tissue, including the aortocaval groove, the aortopulmonary window, both cardiophrenic sinuses and the lower cervical area. Three or four trocars are inserted into the left hemithorax. The operator stays on the left side of the patient in a caudal position to the cameraman, but these positions are not fixed and any improvement in better ergonomics or superior visualization should be taking into account. The monitor is on the right side of the patient. The first trocar T1 (10­12 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 and by CO2 Figure 1 - Patient and trocar positioning insufflations at a maximum of 10 mmHg pressure (fig. 2). The second and third trocars T2, T3(10­12 and 5­7 mm or 10-12mm, respectively) are placed through the third inter-costal space on the anterior axilary line and through the fourth or fifth inter-costal spaces on the mid-clavicle line. Some time we use a forth trocar for retraction (fig 1). For females the incision should be done keeping in mind the important cosmetic problem of the peri ­mammary scars. After a careful pleural cavity exploration, using T1 or T2 we spot the anterior mediastinum. The capnotorax helps us also in the dissection. In order to have this support we need to start all the operations with incision of the mediastinal pleura along the two important landmarks of thymectomy: the phrenic nerve and the internal thoracic artery (fig. 3), allowing the gas dissection to help us. The incision of the mediastinal pleura and the dissection of the thymus begin anterior to the left phrenic nerve and continue into the entire 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 cranial limit of the dissection, at the level of the mediastinal pleura, is the internal thoracic Figure 2 - CO2 insufflations at a maximum of 10 mmHg pressure enlarge the anterior mediastinum space Figure 3 - Landmarks of the anterior mediastinum in thymectomy (right side approach) artery. With camera placed in T2 the operation continues with dissection of the inferior left thymic horn and pericardial fatty tissue. The dissection of Figure 4 - Dissection of the aortopulmonary window Figure 5 - Dissection of the aorto-caval groove Figure 6 - Dissection of the upper left horn Figure 7 - Clipping the thymus vein the thymic tissue together with pericardial fat goes cephalad on the pericardial plane overtaking the median line, to the right of the thymus gland. The contra-laterally mediastinal pleura is opened and the inferior right thymic horn and pericardial fatty tissue is dissected in the same manner. We continue to dissect anterior, retrosternal, the mediastinal pleura being open on the right side till the right mammary pedicle. The posterior dissection continues similar, the pericardium, the aortic arch, the left brachiocephalic vein, and the superior vena cava are visualized and cleaned of all fat tissue or thymus. The most difficult area to dissect is in the aortopulmonary window (fig. 4) and aortocaval groove (fig. 5). At the superior pole, the dissection is performed in the anterior carotidal plane to the internal thoracic artery level. The left superior horn or some time both upper horns may occasionally pass behind, instead of in front of the brahiocephalic vein. This anatomical variety is more difficult to be solved by thoracoscopic approach. We have to be aware of the vagus nerve ant left recurrent laryngeal nerve that goes close and dissect carefully inferior and posterior to the brahiocephalic vein and then superior, to free the cervical parts of the upper horns. Then traction of the upper horns caudally permits the dissection of them behind the brahiocephalic vein, in order to visualize an eventual posterior thymus vein. The thymectomy ends with the identification of the superior part of the gland, the thyreo-thymic ligament section, and freeing of the superior horns from the surrounding tissue. After dissecting the surrounding fascia and cutting the vessels that goes caudally from cervix, upper horns can be mobilized Figure 8 - Landmarks of the anterior mediastinum at the end of thymectomy (right side approach) Figure 9 - Delimit the operation field (right side approach) caudally by applying gentle traction (fig. 6). 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 (fig. 7). 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. Visualization of the right phrenic nerve is necessary to complete the dissection of thymus and fatty tissue. Thymus extraction is quite easily done by enlarging the hole of one of the trocar ports and bagging the piece before extracting it. We prefer to introduce the bag at the beginning of the intervention, this way any small piece of thymus or fatty tissue could be bagged during dissection. The operation ends with the thymic cavity inspection (fig. 8), which can detect possible remnant tissue. Finally, we wash the cavity with warm saline. At the end of the operation one or two drains can be placed in the pleural cavity through the inferior trocar ports. We perform the same operation for TMG. If there is any question of pericardial invasion, we incise the pericardium and take it as part of the resection. The same is true for either or both pleural reflections if there is any question of invasion. Sometimes the phrenic nerve have to be dissected carefully from the tumor. thoracoscopic thymectomy For robotic surgery the patient is positioned similar. The left arm is positioned on a support, extended, axillary region well exposed. The video console is positioned at the head of the operating table. The robotic cart is on the right side of the patient 45° cranial. The ports for the robotic arms are placed as follows: a camera port (12 mm) in 5th intercostals space on the anterior axillary line, and arm ports (8 mm) in 5th intercostals space on midclavicular line for left arm and in the 3rd intercostals space on the anterior axillary line for the right arm. The arms of the robot are then attached to the trocar access points. The instruments are inserted under direct camera control. The left arm has an EndoWrist instrument for to grasp the thymus and the right arm a dissection device that can be an Endo- Dissector, hook, scissor, or ultrasonic shears. The ultrasonic shears has only 4 degrees of freedom and is not as maneuverable as EndoWrist instruments but can be used also for grasping and is not using monopolar electrocoagulation near the heart. I prefer to use a bipolar Micro-forceps for the left arm and a monopolar electrocoagulation scissor for the right arm. In this way we can use at maximum the excellent maneuverability of robotic instruments combining monopolar cautery dissection with bipolar coagulation using a very small forceps useful in the narrow space of the anterior mediastinum. During surgery we inflate the thorax with CO2, 8 or 10 mm Hg. The capnothorax facilitate the dissection, enlarge the space between sternum and pericardium, allowing us to have a better view Robotic assisted unilaterally extended Figure 10 - Dissection continues contra-laterally (left side approach) contra laterally and in the cervical area. After a careful inspection we start the dissection at the left pericardiophrenic angle. We make an incision along the internal mammary artery and another along the phrenic nerve (fig. 9). We start in this way first of all to delimit the space of the thymus and fatty tissue that have to be excised in unilaterally extended robotic assisted thymectomy and secondly permit the CO2 to help us in dissection. We prefer to introduce at the beginning of the intervention the retrieving bag into the thorax. In this way every small part of fatty tissue or thymus dissected can be parked in it. Dissecting from the pericardiophrenic angle in the posterior pericardial plane and anterior retrosternal, the thymus and the fatty tissue is mobilized cranial, till the inominate vein is identified. The fatty tissue from the aortopulmonary window is dissected in the same manner. The excellent view of the robotic system allow us to identify and protégé the phrenic nerve recurrent nerve and vagus. The dissection continue contra laterally (fig. 10), on the right side with the dissection of the inferior thymus horn. At the superior level the thymus and the fatty tissue is dissected along the border of the innominate vein (fig. 11) indentifying the thymic veins, clipping and sectioning them. The dissection continues in the cervical area with the dissection of the upper thymus horns. Sectioning the upper horns vessels coming from the cervical area permit us to mobilize the upper horns caudally by applying gentle traction. There is a detail to be noticed, robotic system does not have force feed-back so Figure 11 - Dissection of thymus from along the border of the innominate vein using the robotic scissor there is no tactile sense. A surgeon have to teach himself to feel with the eyes when is performing robotic surgery. The patients were extubated in the operating room and stayed in the intensive care unit till next morning. Results The study population consisted in 72 male patients (20.2%) and 286 female patients (79.8%), aged 8­70 years. For NTMG we do not operate pactients over 60 years of age. The indication for surgery have been in 34 cases thymic tumors ­ thymoma, and in 324 cases NTMG Our surgical approach for thoracoscopic thymectomy in nontumoral myasthenia gravis was initially left-side. After the first 30 cases, we also performed right-side thoracoscopy. We now routinely choose between the right or the left side approach depending on the CT aspect of the anterior mediastinum, adding whenever is necessary a cervical approach either in tumoral or nontumoral lesions. Extensive dissection in the region of the thyroid and lateral neck, through a separate collar incision was not routinely performed. The low probability of finding aberrant thymic remnants in these locations did not justify this approach as a standard procedure. Minicervicotomies were performed on 7 patients due to cervical extensions of the thymus. We have used the right thoracoscopic approach in 28.5% (102 cases), in 10 cases with the help of da Vinci robotic system and the left thoracoscopic approach in 71.5% (256 cases), 29 robotic. Robotic approach have been used in 29 patients with myasthenia gravis without tumor and in 10 patients with myasthenia gravis with thoracic tumor (stage I or IIa Masaoka thymomas) There were no deaths or major complications in these 358 patients and morbidity was observed in 16 cases (4.46%): 10 patients previously reported (10) (severe postoperative myasthenia crisis in 1 patient who needed mechanical ventilation for 5 days, 2 with contralateral pneumothorax after drain removal, 3 with hemothorax that required emergent reintervention, and 4 with prolonged pleural drainage) and 4 cases with postoperative pneumonia and 2 patients with chylothorax after thymoma resection. The following histological diagnoses (fig. 12) were made: normal thymus in 20 cases, involuted thymus in 88 cases and thymus hypertrophy (hyperplastic thymus) in 216 cases. The average weight of the thymus was 110g (range: 45-155 g). For TMG patients, in 2 cases the initial thoracoscopic evaluation have shown invasion of the aortic arch adventitia in one case and bronchocephalic trunk in the other one, an open transsternal approach solved these post-operatory stage IIIb Masaoka cortical thymoma cases. From the other 32 cases 25 have been stage I Masaoka, 4 stage II and 3 stage IIIa with invasion only of the pericard. The pathological results have been cortical thymoma in 16 patients, mixed thymoma in 8 patients, medular thymoma in 6 patients and well differentiated thymic carcinoma (WDTC) in 2 patients. Postoperative treatment only for stage III Masaoka without any sign of recurrence during the follow-up period of 3 to 92 months. The mean duration of hospitalization was 3.6 days (range 2-18 days). All thymoma patients survived without any sign of recurrence during the follow-up period of 3 to 92 months. Discussion After a period of lack of interest in thoracoscopy a number of recent advances regenerated enthusiasm in thoracic surgeons about the thoracoscopic procedures. Without the aid of modern anesthetic techniques such as endotracheal intubation and one lung ventilation, the complicated thoracoscopic procedures, commonly performed today, would be impossible. Like the cervical approach(11;12), the thoracos- Figure 12 - Histological diagnosis distribution copic approach for anterior mediastinum masses 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 (13). 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 (11) and advanced laparoscopic procedures (splenectomy, colorectal, and hepatic laparoscopic surgery). Yim and colleagues (12) first proposed a rightsided approach for VATS thymectomy and recommended this approach for several reasons that are valuable for thoracoscopic approach of anterior mediastinal masses: (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 (14), we believe that thoracoscopic approach for anterior mediastinum 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 anterior mediastinum is easier from the left approach than dissection of the left part of the anterior mediastinum from the right approach. Opening of the contralateral 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 contralateral costomediastinal sinus (sparing the contralateral phrenic nerve, of course), we perform this procedure. Insufflations up to 10 mmHg facilitates pulmonary collapse and makes mediastinal dissection easier with minimal clinical hemodynamic impact (15). Thymoma, which is a representative tumor derived from the thymic epithelium, is well known for its heterogeneous oncologic behavior, variability in histologic appearance, and association with autoimmune diseases, represented by myasthenia gravis (16). The cornerstone of therapy is the complete removal of the tumor in addition to a total thymectomy (17). Simply extirpating the lesion and leaving residual thymus has been associated with the later development of myasthenia gravis and recurrence (18). In patients who have myasthenia gravis and present with a thymoma, the importance of the complete removal of the thymus gland cannot be overstated(19). Several authors have reported robotic thymectomies with excision of thymomas, although the experience has been limited (20-23). The da Vinci surgical robotic system offers advanced visual control and superior maneuverability of the surgical instruments, and hand movements in the grips of the console are naturally and intuitively transmitted to the robot's instruments. With 7° of freedom in movement of the instrument tip and a possible rotation of 360°, it is superior to a surgeon's hand in open surgery. This facilitates gentle and precise dissection within a small area with vulnerable large vessels and nerves. There were no major incidents during the operations that were performed either thoracoscopically or robotically. It should be noted that, in one case of bleeding from the brachiocephalic vein, lesion of the insertion of the right internal mammary vein, in a left robotic approach, we were able to suture the lesion with 6-0 prolene. The versatile robotic instruments allowed to perform this maneuver at an angle that would have not been possible using a thoracoscopic approach. Because the movements in robotic surgery are intuitive and the visualization is superior to traditional surgical techniques, proctoring and training in this advanced minimally invasive procedure is more rapid and efficient than with a classic thoracoscopic approach or transcervical thymectomy (11;12). We encountered no brachial plexus injury, as was reported by Mong-Wei Lin and co-workers (24) and Ravindra Pandey and co-workers (25) using a robotic approach, but we have taken extreme care regarding patient positioning, avoiding 90° abduction in the placement of the shoulder joint and placing a roll under the arm and axilla in these patients. The anaesthesiologist and the assistant surgeon were constantly looking for any injury that the robotic arms could potentially cause. Continuous communication between the console surgeon and the other two members of the surgical-anaesthesiology team and careful procedure planning are the keys of good results with robotic surgery. In conclusion we consider that the thoracoscopic surgery, classic or robotic assisted for nontumoral and tumoral myasthenia gravis is no doubt beneficially in selected cases in relation to no mortality, low morbidity and good oncology outcome. Reference List 1. Landreneau RJ, Mack MJ, Hazelrigg SR, Dowling RD, Acuff TE, Magee MJ, Ferson PF. Video-assisted thoracic surgery: basic technical concepts and intercostal approach strategies. Ann Thorac Surg 1992 October;54(4):800-7. 2. Landreneau RJ, Dowling RD, Castillo WM, Ferson PF. Thoracoscopic resection of an anterior mediastinal tumor. Ann Thorac Surg 1992 July;54(1):142-4. 3. Lewis RJ, Caccavale RJ, Sisler GE. Imaged thoracoscopic surgery: a new thoracic technique for resection of mediastinal cysts. Ann Thorac Surg 1992 February;53(2):318-20. 4. Hazelrigg SR, Landreneau RJ, Mack MJ, Acuff TE. Thoracoscopic resection of mediastinal cysts. Ann Thorac Surg 1993 September;56(3):659-60. 5. Naunheim KS, Andrus CH. Thoracoscopic drainage and resection of giant mediastinal cyst. Ann Thorac Surg 1993 January;55(1):156-8. 6. Ashton RC, Jr., McGinnis KM, Connery CP, Swistel DG, Ewing DR, Derose JJ, Jr. Totally endoscopic robotic thymectomy for myasthenia gravis. Ann Thorac Surg 2003 February;75(2): 569-71. 7. Rea F, Marulli G, Bortolotti L, Feltracco P, Zuin A, Sartori F. Experience with the "da Vinci" robotic system for thymectomy in patients with myasthenia gravis: report of 33 cases. Ann Thorac Surg 2006 February;81(2):455-9. 8. Popescu I, Tomulescu V, Ion V, Tulbure D. Thymectomy by thoracoscopic approach in myasthenia gravis. Surg Endosc 2002 April;16(4):679-84. 9. Tomulescu V, Ion V, Kosa A, Popescu I. [Thoracoscopic thymectomy in the treatment of myasthenia gravis]. Chirurgia (Bucur ) 2005 May;100(3):215-22. 10. Tomulescu V, Ion V, Kosa A, Sgarbura O, Popescu I. Thoracoscopic thymectomy mid-term results. Ann Thorac Surg 2006 September;82(3):1003-7. 11. Calhoun RF, Ritter JH, Guthrie TJ, Pestronk A, Meyers BF, Patterson GA, Pohl MS, Cooper JD. Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients. Ann Surg 1999 October;230(4):555-9. 12. Shrager JB. Extended transcervical thymectomy: the ultimate minimally invasive approach. Ann Thorac Surg 2010 June;89(6):S2128-S2134. 13. Yim AP, Lee TW, Izzat MB, Wan S. Place of video-thoracoscopy in thoracic surgical practice. World J Surg 2001 February;25(2):157-61. 14. Mineo TC, Pompeo E, Ambrogi V. Video-assisted thoracoscopic thymectomy: from the right or from the left? J Thorac Cardiovasc Surg 1997 September;114(3):516-7. 15. Tomescu D, Grigorescu B, Nitulescu R, Tomulescu V, Popescu I, Tulbure D. [Hemodynamic changes induced by positive pressure capnothorax during thoracoscopic thymectomy]. Chirurgia (Bucur ) 2007 May;102(3):263-70. 16. Kondo K, Yoshizawa K, Tsuyuguchi M, Kimura S, Sumitomo M, Morita J, Miyoshi T, Sakiyama S, Mukai K, Monden Y. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 2004 April;77(4):1183-8. 17. Singhal S, Shrager JB, Rosenthal DI, LiVolsi VA, Kaiser LR. Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg 2003 November;76(5):1635-41. 18. Kaiser LR. Surgical treatment of thymic epithelial neoplasms. Hematol Oncol Clin North Am 2008 June;22(3):475-88. 19. Kondo K, Monden Y. Myasthenia gravis appearing after thymectomy for thymoma. Eur J Cardiothorac Surg 2005 July;28(1):22-5. 20. Bodner J, Wykypiel H, Greiner A, Kirchmayr W, Freund MC, Margreiter R, Schmid T. Early experience with robot-assisted surgery for mediastinal masses. Ann Thorac Surg 2004 July;78(1):259-65. 21. Rea F, Marulli G, Bortolotti L, Feltracco P, Zuin A, Sartori F. Experience with the "da Vinci" robotic system for thymectomy in patients with myasthenia gravis: report of 33 cases. Ann Thorac Surg 2006 February;81(2):455-9. 22. Ruckert JC, Ismail M, Swierzy M, Sobel H, Rogalla P, Meisel A, Wernecke KD, Ruckert RI, Muller JM. Thoracoscopic thymectomy with the da Vinci robotic system for myasthenia gravis. Ann N Y Acad Sci 2008;1132:329-35. 23. Savitt MA, Gao G, Furnary AP, Swanson J, Gately HL, Handy JR. Application of robotic-assisted techniques to the surgical evaluation and treatment of the anterior mediastinum. Ann Thorac Surg 2005 February;79(2):450-5. 24. Lin MW, Chang YL, Huang PM, Lee YC. Thymectomy for nonthymomatous myasthenia gravis: a comparison of surgical methods and analysis of prognostic factors. Eur J Cardiothorac Surg 2010 January;37(1):7-12. 25. Pandey R, Elakkumanan LB, Garg R, Jyoti B, Mukund C, Chandralekha, Punj J, Vanlal D. Brachial plexus injury after robotic-assisted thoracoscopic thymectomy. J Cardiothorac Vasc Anesth 2009 August;23(4):584-6. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Fundeni Hospital de Gruyter

Minimally invasive approach for tumoral and non tumoral myasthenia gravis; from thoracoscopic to robotic surgery

Tomulescu, V.
Annals of Fundeni Hospital , Volume 16 – Dec 1, 2011
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Abstract

The purpose of this study is to evaluate whether a thoracoscopic resection assisted or not by the computer can be successfully performed to treat nontumoral myasthenia gravis and early-stage tumors of the anterior mediastinum with results as good as in open approach. There have been 358 patients with tumoral (TMG) and nontumoral myasthenia gravis (NTMG) that have suffered an extended thoracoscopic thymectomy in our center between April 1999 and April 2010. 319 patients have been operated using a classic thoracoscopic approach and 39 using a robotic approach. The study population consisted in 72 male patients (20.2%) and 286 female patients (79.8%), aged 8­70 years. For NTMG we do not operate pactients over 60 years of age. The indication for surgery have been in 34 cases thymic tumors ­ thymoma, and in 324 cases NTMG. The following histological diagnoses (fig 12) were made for NTMG: normal thymus in 20 cases, involuted thymus in 88 cases and thymus hypertrophy (hyperplastic thymus) in 216 cases. The pathological results for TMG have been cortical thymoma in 16 patients, mixed thymoma in 8 patients, medular thymoma in 6 patients and well differentiated thymic carcinoma (WDTC) in 2 patients. Postoperative treatment only for stage III Masaoka without any sign of recurrence during the follow-up period of 3 to 92 months. The mean duration of hospitalization was 3.6 days (range 2-18 days). All thymoma patients survived without any sign of recurrence during the follow-up period of 3 to 92 months. In conclusion we consider that the thoracoscopic surgery, classic or robotic assisted for nontumoral and tumoral myasthenia gravis is no doubt beneficially in selected cases in relation to no mortality, low morbidity and good oncology outcome. Key words: myasthenia gravis, thymoma, thoracoscopic surgery, robotic surgery Introduction The standard surgical procedure for the treatment of anterior mediastinal masses has been the transsternal approach. Some reports have shown that thoracoscopic resection of the anterior mediastinal masses is technically feasible in selected patients (1). In 1992, Landrenau et al.(2) and Lewis et al.(3) and in 1993, Hazelrigg et al.(4), and Naunheim and Andrus(5) reported their experience using the miniinvasive approach (video-assisted thoracoscopic surgery) on some mediastinal lesions. Minimally invasive techniques have become increasingly popular due to their low procedural morbidity and mortality, improved cosmesis, Address for correspondence: Victor Tomulescu, MD, "Dan Setlacec" Center for General Surgery and Liver Transplantation, Fundeni Clinical Institute, Sos. Fundeni, 258, 022328, Bucharest, Romania, e-mail: victor.tomulescu@gmail.com lesser degree of access trauma, and equivalent efficacy compared to conventional open techniques. In 2001, Yoshino described the first robotic thymectomy in the treatment of small thymoma. In 2003, Ashton and Rea published a case report on robotic thymectomy in MG using two different approaches: the first adopted a right-sided approach with completion of the operation through a left-sided approach, the second used a leftsided approach only(6;7). Materials and methods We have started the thoracoscopic approach for anterior mediastinal lesions in 1999. At the beginning we have performed only thoracoscopic thymectomy for nontumoral myasthenia gravis and then, with growing experience to other lesions of anterior mediastinum(8;9). Since April 1999, a thoracoscopic approach has been used in all patients admitted in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute with either nontumoral myasthenia gravis (NTMG) or stage I and IIa Masaoka thymomas (TMG). We have start the robotic approach in 2008 and robotic approach of anterior mediastinum have become one of the priorities of our department. There have been 358 patients with tumoral and nontumoral myasthenia gravis (NTMG) that have suffered an extended thoracoscopic thymectomy in our center between April 1999 and April 2010. 319 patients have been operated using a classic thoracoscopic approach and 39 using a robotic approach The purpose of this study is to evaluate whether a thoracoscopic resection assisted or not by the computer can be successfully performed to treat nontumoral myasthenia gravis and earlystage tumors of the anterior mediastinum with results as good as in open approach Informed consent was obtained from all patients. The patients were informed about the disease, different treatment options, surgical approaches and potential benefits and complications. Our study was approved by the Fundeni Clinical Institute Ethics Committee in accordance with the ethical standards of the Helsinki Declaration of 1975. The diagnose of MG were based on patient's histories, physical examinations, positive responses to anticholinesterase agents and electrophysiology studies. Preoperative diagnostic tests included spirometry and a computed tomography (CT) scan. For thymomas CT image considerations included the location of the tumor in the anterior mediastinum, a distinct fat plane between the tumor and vital organ, unilateral tumor predominance, tumor encapsulation, existence of residual normalappearing thymic tissue, and no mass compression effect. The enrollees were expected to be free of pleural effusion, pericardial effusion, paralysis of hemidiaphragm, and the encasement of great vessels We considered that favourable outcomes requires highly coordinated teamwork involving a strong collaboration between neurologists, surgeons, and anesthesiologists in making appropriate decisions on selection of patients, therapeutic options, and timing of surgery. All of the patients received specific treatment for at least 3 months before surgery in the Department of Neurology of our institute. Patients were considered suitable for a surgical procedure only when evidence showed good treatment tolerance and a stable quantitative myasthenia gravis (QMG) score of at least 10 points. For NTMG we did not operate patients with pure ocular myasthenia gravis because we considered that the indication for thymectomy in ocular myasthenia gravis remained controversial. Surgical technique Thoracoscopic technique The procedure is a thoracoscopic unilaterally extended thymectomy that routinely removed the entire gland and all anterior mediastinal perithymic fatty tissue, including the aortocaval groove, the aortopulmonary window, both cardiophrenic sinuses and the lower cervical area. Three or four trocars are inserted into the left hemithorax. The operator stays on the left side of the patient in a caudal position to the cameraman, but these positions are not fixed and any improvement in better ergonomics or superior visualization should be taking into account. The monitor is on the right side of the patient. The first trocar T1 (10­12 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 and by CO2 Figure 1 - Patient and trocar positioning insufflations at a maximum of 10 mmHg pressure (fig. 2). The second and third trocars T2, T3(10­12 and 5­7 mm or 10-12mm, respectively) are placed through the third inter-costal space on the anterior axilary line and through the fourth or fifth inter-costal spaces on the mid-clavicle line. Some time we use a forth trocar for retraction (fig 1). For females the incision should be done keeping in mind the important cosmetic problem of the peri ­mammary scars. After a careful pleural cavity exploration, using T1 or T2 we spot the anterior mediastinum. The capnotorax helps us also in the dissection. In order to have this support we need to start all the operations with incision of the mediastinal pleura along the two important landmarks of thymectomy: the phrenic nerve and the internal thoracic artery (fig. 3), allowing the gas dissection to help us. The incision of the mediastinal pleura and the dissection of the thymus begin anterior to the left phrenic nerve and continue into the entire 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 cranial limit of the dissection, at the level of the mediastinal pleura, is the internal thoracic Figure 2 - CO2 insufflations at a maximum of 10 mmHg pressure enlarge the anterior mediastinum space Figure 3 - Landmarks of the anterior mediastinum in thymectomy (right side approach) artery. With camera placed in T2 the operation continues with dissection of the inferior left thymic horn and pericardial fatty tissue. The dissection of Figure 4 - Dissection of the aortopulmonary window Figure 5 - Dissection of the aorto-caval groove Figure 6 - Dissection of the upper left horn Figure 7 - Clipping the thymus vein the thymic tissue together with pericardial fat goes cephalad on the pericardial plane overtaking the median line, to the right of the thymus gland. The contra-laterally mediastinal pleura is opened and the inferior right thymic horn and pericardial fatty tissue is dissected in the same manner. We continue to dissect anterior, retrosternal, the mediastinal pleura being open on the right side till the right mammary pedicle. The posterior dissection continues similar, the pericardium, the aortic arch, the left brachiocephalic vein, and the superior vena cava are visualized and cleaned of all fat tissue or thymus. The most difficult area to dissect is in the aortopulmonary window (fig. 4) and aortocaval groove (fig. 5). At the superior pole, the dissection is performed in the anterior carotidal plane to the internal thoracic artery level. The left superior horn or some time both upper horns may occasionally pass behind, instead of in front of the brahiocephalic vein. This anatomical variety is more difficult to be solved by thoracoscopic approach. We have to be aware of the vagus nerve ant left recurrent laryngeal nerve that goes close and dissect carefully inferior and posterior to the brahiocephalic vein and then superior, to free the cervical parts of the upper horns. Then traction of the upper horns caudally permits the dissection of them behind the brahiocephalic vein, in order to visualize an eventual posterior thymus vein. The thymectomy ends with the identification of the superior part of the gland, the thyreo-thymic ligament section, and freeing of the superior horns from the surrounding tissue. After dissecting the surrounding fascia and cutting the vessels that goes caudally from cervix, upper horns can be mobilized Figure 8 - Landmarks of the anterior mediastinum at the end of thymectomy (right side approach) Figure 9 - Delimit the operation field (right side approach) caudally by applying gentle traction (fig. 6). 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 (fig. 7). 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. Visualization of the right phrenic nerve is necessary to complete the dissection of thymus and fatty tissue. Thymus extraction is quite easily done by enlarging the hole of one of the trocar ports and bagging the piece before extracting it. We prefer to introduce the bag at the beginning of the intervention, this way any small piece of thymus or fatty tissue could be bagged during dissection. The operation ends with the thymic cavity inspection (fig. 8), which can detect possible remnant tissue. Finally, we wash the cavity with warm saline. At the end of the operation one or two drains can be placed in the pleural cavity through the inferior trocar ports. We perform the same operation for TMG. If there is any question of pericardial invasion, we incise the pericardium and take it as part of the resection. The same is true for either or both pleural reflections if there is any question of invasion. Sometimes the phrenic nerve have to be dissected carefully from the tumor. thoracoscopic thymectomy For robotic surgery the patient is positioned similar. The left arm is positioned on a support, extended, axillary region well exposed. The video console is positioned at the head of the operating table. The robotic cart is on the right side of the patient 45° cranial. The ports for the robotic arms are placed as follows: a camera port (12 mm) in 5th intercostals space on the anterior axillary line, and arm ports (8 mm) in 5th intercostals space on midclavicular line for left arm and in the 3rd intercostals space on the anterior axillary line for the right arm. The arms of the robot are then attached to the trocar access points. The instruments are inserted under direct camera control. The left arm has an EndoWrist instrument for to grasp the thymus and the right arm a dissection device that can be an Endo- Dissector, hook, scissor, or ultrasonic shears. The ultrasonic shears has only 4 degrees of freedom and is not as maneuverable as EndoWrist instruments but can be used also for grasping and is not using monopolar electrocoagulation near the heart. I prefer to use a bipolar Micro-forceps for the left arm and a monopolar electrocoagulation scissor for the right arm. In this way we can use at maximum the excellent maneuverability of robotic instruments combining monopolar cautery dissection with bipolar coagulation using a very small forceps useful in the narrow space of the anterior mediastinum. During surgery we inflate the thorax with CO2, 8 or 10 mm Hg. The capnothorax facilitate the dissection, enlarge the space between sternum and pericardium, allowing us to have a better view Robotic assisted unilaterally extended Figure 10 - Dissection continues contra-laterally (left side approach) contra laterally and in the cervical area. After a careful inspection we start the dissection at the left pericardiophrenic angle. We make an incision along the internal mammary artery and another along the phrenic nerve (fig. 9). We start in this way first of all to delimit the space of the thymus and fatty tissue that have to be excised in unilaterally extended robotic assisted thymectomy and secondly permit the CO2 to help us in dissection. We prefer to introduce at the beginning of the intervention the retrieving bag into the thorax. In this way every small part of fatty tissue or thymus dissected can be parked in it. Dissecting from the pericardiophrenic angle in the posterior pericardial plane and anterior retrosternal, the thymus and the fatty tissue is mobilized cranial, till the inominate vein is identified. The fatty tissue from the aortopulmonary window is dissected in the same manner. The excellent view of the robotic system allow us to identify and protégé the phrenic nerve recurrent nerve and vagus. The dissection continue contra laterally (fig. 10), on the right side with the dissection of the inferior thymus horn. At the superior level the thymus and the fatty tissue is dissected along the border of the innominate vein (fig. 11) indentifying the thymic veins, clipping and sectioning them. The dissection continues in the cervical area with the dissection of the upper thymus horns. Sectioning the upper horns vessels coming from the cervical area permit us to mobilize the upper horns caudally by applying gentle traction. There is a detail to be noticed, robotic system does not have force feed-back so Figure 11 - Dissection of thymus from along the border of the innominate vein using the robotic scissor there is no tactile sense. A surgeon have to teach himself to feel with the eyes when is performing robotic surgery. The patients were extubated in the operating room and stayed in the intensive care unit till next morning. Results The study population consisted in 72 male patients (20.2%) and 286 female patients (79.8%), aged 8­70 years. For NTMG we do not operate pactients over 60 years of age. The indication for surgery have been in 34 cases thymic tumors ­ thymoma, and in 324 cases NTMG Our surgical approach for thoracoscopic thymectomy in nontumoral myasthenia gravis was initially left-side. After the first 30 cases, we also performed right-side thoracoscopy. We now routinely choose between the right or the left side approach depending on the CT aspect of the anterior mediastinum, adding whenever is necessary a cervical approach either in tumoral or nontumoral lesions. Extensive dissection in the region of the thyroid and lateral neck, through a separate collar incision was not routinely performed. The low probability of finding aberrant thymic remnants in these locations did not justify this approach as a standard procedure. Minicervicotomies were performed on 7 patients due to cervical extensions of the thymus. We have used the right thoracoscopic approach in 28.5% (102 cases), in 10 cases with the help of da Vinci robotic system and the left thoracoscopic approach in 71.5% (256 cases), 29 robotic. Robotic approach have been used in 29 patients with myasthenia gravis without tumor and in 10 patients with myasthenia gravis with thoracic tumor (stage I or IIa Masaoka thymomas) There were no deaths or major complications in these 358 patients and morbidity was observed in 16 cases (4.46%): 10 patients previously reported (10) (severe postoperative myasthenia crisis in 1 patient who needed mechanical ventilation for 5 days, 2 with contralateral pneumothorax after drain removal, 3 with hemothorax that required emergent reintervention, and 4 with prolonged pleural drainage) and 4 cases with postoperative pneumonia and 2 patients with chylothorax after thymoma resection. The following histological diagnoses (fig. 12) were made: normal thymus in 20 cases, involuted thymus in 88 cases and thymus hypertrophy (hyperplastic thymus) in 216 cases. The average weight of the thymus was 110g (range: 45-155 g). For TMG patients, in 2 cases the initial thoracoscopic evaluation have shown invasion of the aortic arch adventitia in one case and bronchocephalic trunk in the other one, an open transsternal approach solved these post-operatory stage IIIb Masaoka cortical thymoma cases. From the other 32 cases 25 have been stage I Masaoka, 4 stage II and 3 stage IIIa with invasion only of the pericard. The pathological results have been cortical thymoma in 16 patients, mixed thymoma in 8 patients, medular thymoma in 6 patients and well differentiated thymic carcinoma (WDTC) in 2 patients. Postoperative treatment only for stage III Masaoka without any sign of recurrence during the follow-up period of 3 to 92 months. The mean duration of hospitalization was 3.6 days (range 2-18 days). All thymoma patients survived without any sign of recurrence during the follow-up period of 3 to 92 months. Discussion After a period of lack of interest in thoracoscopy a number of recent advances regenerated enthusiasm in thoracic surgeons about the thoracoscopic procedures. Without the aid of modern anesthetic techniques such as endotracheal intubation and one lung ventilation, the complicated thoracoscopic procedures, commonly performed today, would be impossible. Like the cervical approach(11;12), the thoracos- Figure 12 - Histological diagnosis distribution copic approach for anterior mediastinum masses 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 (13). 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 (11) and advanced laparoscopic procedures (splenectomy, colorectal, and hepatic laparoscopic surgery). Yim and colleagues (12) first proposed a rightsided approach for VATS thymectomy and recommended this approach for several reasons that are valuable for thoracoscopic approach of anterior mediastinal masses: (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 (14), we believe that thoracoscopic approach for anterior mediastinum 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 anterior mediastinum is easier from the left approach than dissection of the left part of the anterior mediastinum from the right approach. Opening of the contralateral 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 contralateral costomediastinal sinus (sparing the contralateral phrenic nerve, of course), we perform this procedure. Insufflations up to 10 mmHg facilitates pulmonary collapse and makes mediastinal dissection easier with minimal clinical hemodynamic impact (15). Thymoma, which is a representative tumor derived from the thymic epithelium, is well known for its heterogeneous oncologic behavior, variability in histologic appearance, and association with autoimmune diseases, represented by myasthenia gravis (16). The cornerstone of therapy is the complete removal of the tumor in addition to a total thymectomy (17). Simply extirpating the lesion and leaving residual thymus has been associated with the later development of myasthenia gravis and recurrence (18). In patients who have myasthenia gravis and present with a thymoma, the importance of the complete removal of the thymus gland cannot be overstated(19). Several authors have reported robotic thymectomies with excision of thymomas, although the experience has been limited (20-23). The da Vinci surgical robotic system offers advanced visual control and superior maneuverability of the surgical instruments, and hand movements in the grips of the console are naturally and intuitively transmitted to the robot's instruments. With 7° of freedom in movement of the instrument tip and a possible rotation of 360°, it is superior to a surgeon's hand in open surgery. This facilitates gentle and precise dissection within a small area with vulnerable large vessels and nerves. There were no major incidents during the operations that were performed either thoracoscopically or robotically. It should be noted that, in one case of bleeding from the brachiocephalic vein, lesion of the insertion of the right internal mammary vein, in a left robotic approach, we were able to suture the lesion with 6-0 prolene. The versatile robotic instruments allowed to perform this maneuver at an angle that would have not been possible using a thoracoscopic approach. Because the movements in robotic surgery are intuitive and the visualization is superior to traditional surgical techniques, proctoring and training in this advanced minimally invasive procedure is more rapid and efficient than with a classic thoracoscopic approach or transcervical thymectomy (11;12). We encountered no brachial plexus injury, as was reported by Mong-Wei Lin and co-workers (24) and Ravindra Pandey and co-workers (25) using a robotic approach, but we have taken extreme care regarding patient positioning, avoiding 90° abduction in the placement of the shoulder joint and placing a roll under the arm and axilla in these patients. The anaesthesiologist and the assistant surgeon were constantly looking for any injury that the robotic arms could potentially cause. Continuous communication between the console surgeon and the other two members of the surgical-anaesthesiology team and careful procedure planning are the keys of good results with robotic surgery. In conclusion we consider that the thoracoscopic surgery, classic or robotic assisted for nontumoral and tumoral myasthenia gravis is no doubt beneficially in selected cases in relation to no mortality, low morbidity and good oncology outcome. Reference List 1. Landreneau RJ, Mack MJ, Hazelrigg SR, Dowling RD, Acuff TE, Magee MJ, Ferson PF. Video-assisted thoracic surgery: basic technical concepts and intercostal approach strategies. Ann Thorac Surg 1992 October;54(4):800-7. 2. Landreneau RJ, Dowling RD, Castillo WM, Ferson PF. Thoracoscopic resection of an anterior mediastinal tumor. Ann Thorac Surg 1992 July;54(1):142-4. 3. Lewis RJ, Caccavale RJ, Sisler GE. Imaged thoracoscopic surgery: a new thoracic technique for resection of mediastinal cysts. Ann Thorac Surg 1992 February;53(2):318-20. 4. Hazelrigg SR, Landreneau RJ, Mack MJ, Acuff TE. Thoracoscopic resection of mediastinal cysts. Ann Thorac Surg 1993 September;56(3):659-60. 5. Naunheim KS, Andrus CH. 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Journal

Annals of Fundeni Hospital – de Gruyter

Published: Dec 1, 2011

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