MINISTRY OF EDUCATION MINISTRY OF AND TRAINING NATIONAL DEFENCE VIETNAM MILITARY MEDICAL UNIVERSITY LE VIET ANH STUDY ON APPLICATION OF VIDEO-ASSISTED THORACOSCOPIC SURGERY FOR THYMOMA WITH MYASTHENIA GRAVIS AT MILITARY HOSPITAL 103 Specialized: Surgery Code: 9720104 SUMMARY OF DOCTORAL THESIS HANOI – 2019 THE STUDY ARE COMPLETED AT VIETNAM MILITARY MEDICAL UNIVERSITY Scientific Supervisor: Assoc Prof Nguyen Truong Giang, MD, PhD Assoc Prof Nguyen Van Nam, MD, PhD Reviewer 1: Assoc Prof., MD, PhD Reviewer 2: Assoc Prof., MD, PhD Reviewer 3: Assoc Prof., MD, PhD The Thesis will be presented at the Military Medical Academy At the time:……./… …/20 This thesis can be found at: The National Library Military Medical University Library ………………………………… ABBREVIATIONS AAL Anterior axillary line CSR Chemical shift ratio CT Computed tomography MRI Magnetic resonance imaging MAL Mid-axillary line MCL Midclavicular line MG Myasthenia Gravis ICU Intensive care unit ICS Intercostal space 10 VATS video-assisted thoracoscopic surgery INTRODUCTION Thymoma is a rare epithelial tumor of the thymus but the most common mediastinal tumor in adults, accounting for 15% -21.7% of mediastinal tumors and 47% of anterior mediastinum tumors, about 0.2% -1.5% of all malignant tumors Research by Strollo DC (1997) shows that thymoma is common in adults, Myasthenia Gravis (MG) occurs in approximately 30% to 50% of patients with thymoma In comparison, only 15% of patients with MG have a thymoma MG is also known as an autoimmune disease that is related to the thymus's activity and pathological disorders The diagnosis of thymoma with MG plays an important role There are many diagnostic methods, the most common is chest computerized tomography (CT) and magnetic resonance imaging (MRI) Many authors have affirmed that when a thymoma with MG was a diagnosis, thymectomy is a first-choice treatment and most effective However, the results also depend on many factors such as pre-operative patient's status, surgical method, postoperative treatment… Up to date, there are many methods for surgery to remove thymoma and thymus, such as trans-sternal, transcervical, thoracotomy approach, especially Minimal invasive surgery: videoassisted thoracoscopic surgery (VATS) The surgery requirement is to remove all of the thymoma, the thymus, and the mediastinal fat The choice of surgical method is extremely important Classic trans-sternal surgery causes much chest damage with severe pain, easily affected by respiratory function, or having sternities complications Transcervical surgery is difficult to remove all the thymoma and thymus gland, especially in cases of thymoma and thymus enlargement, located at the lower pole The VATS is considered by many authors to have many advantages: less pain, less impact on respiration, early recovery With many years of treatment of MG, thymoma, and more than 10 years of experience in VATS, Department of Thoracic Surgery - Military Hospital 103 has made initial success in treatment thymoma with MG by VATS However, the question is whether the VATS for treating thymoma with MG will completely remove thymoma, thymus and mediastinal fat as well as open surgery and how is the result of that treatment method It is necessary to have a research and systematic evaluation of the application of VATS for the treatment of thymoma with MG Therefore, stemming from practical demands mentioned above, we carried out the thesis: "Study on application of videoassisted thoracoscopic surgery for thymoma with Myasthenia Gravis at Military Hospital 103" with two purposes: Review some clinical, imaging and histopathological characteristics of thymoma with Myasthenia Gravis performed by VATS Evaluate results of VATS for thymoma with Myasthenia Gravis at Military Hospital 103 The new contributions of the thesis are as follow: The thesis has described some clinical features of thymoma with MG at Military Hospital 103 by VATS in patients age from 21-70, duration of the disease is less than year, MG class I and IIA The thesis has described some features of imaging, histopathology of thymoma with myasthenia gravis at Military Hospital 103 with CT imaging: thymoma are located in every position, round or oval shape, the high degree of enhancement and level of drug absorbed On MRI: round and oval shape; smooth border or lobes; with fiber capsulate, CSR = 1.04 ± 0.17 Histopathology: met all types, most of them are type AB and B2 (29.5%), none of the thymus carcinoma; the largest size is type B2 and the smallest size is type A The thesis has shown that the effectiveness of VATS for treatment thymoma with myasthenia gravis at Military Hospital 103 with a complete cure rate and improved after surgery increases with follow-up time: month: 85.3%, months: 87.9%,> year: 94.3% The composition of the thesis: The thesis has 132 pages Introduction: pages; Overview: 32 pages; Objects and methods: 27 pages; Results: 32 pages; Discussion: 36 pages; Conclusion: 02 pages; Recommendation: 01 page 136 references: 21 Vietnamese references and 115 English references CHAPTER 1: OVERVIEW 1.2 Characteristics of clinical, paraclinical of thymoma with Myasthenia Gravis 1.2.1 Clinical of thymoma with Myasthenia Gravis 1.2.1.1 Symptoms * Thymoma: from asymptomatic to nonspecific signs such as anorexia, weight loss, chest pain, shortness of breath, cough especially associated with MG * MG: MG symptoms change during the day (heavier in the morning, the rest is better, the more active is heavier) 1.2.1.3 The diagnosis of myasthenia gravis + Test Tensilon (Edrophonium) or Prostigmin + Test Jolly 1.2.2 Paraclinical of thymoma with Myasthenia Gravis 1.2.2.4 Chest CT Chest CT can easily identify not only thymoma but also normal thymus On chest CT, we can see the following signs: - Spherical or multi-lobed - The density of gland is equal or exceeds muscle of chest wall - Including fat - Calcification in the mass - One-sided development or at the middle line 1.2.2.6 MRI CHT is a new modern technique applied in the diagnosis of thymus and thymoma The authors calculated the chemical shift ratio (CSR - chemical shift ratio) CSR is statistically significant in distinguishing thymoma from normal thymus or hyperplasia 1.2.3 Staging of MG and thymoma * MG staging MG of Perlo-Osserman classification - 1979 + Class I: ocular involvement only + Class IIA: mid generalized MG: generalized muscle involvement but no pulmonary involvement + Class IIB: moderately generalized MG: bulbar manifestations + Class III: rapid progression of generalized bulbar disease and weakening of breathing muscle + Class IV: late severe MG: like class III but progressive symptoms in many years * Thymoma staging of Masaoka + Stage I: Grossly and microscopically completely encapsulated tumor + Stage II: Macroscopic invasion into thymic or surrounding fatty tissue, or mediastinal pleura or pericardium and microscopic transcapsular invasion + Stage III: Macroscopic invasion into neighboring organs: pericardium, great blood vessels, or lung + Stage IV: - IVa: Pleural or pericardial metastases - IVb: Lymphogenous or hematogenous metastasis 1.3 Surgery method for thymoma with myasthenia gravis The basic purpose of VATS for thymoma with MG is to remove all of the thymoma, the thymus, and the mediastinal fat 1.3.2 Surgery methods 1.3.2.1 Open surgery + Trans-sternal approach + Thoracotomy approach 1.3.2.2 Video-assisted transcervical approach 1.3.2.3 VATS for thymoma with MG First described by Sugarbaker in 1993 In Vietnam, the first case of VATS for MG was performed at Cho Ray Hospital in 2004 Military Hospital 103 was performed in 9/2008 CHAPTER 2: OBJECTS AND METHODS 2.1 Objects Sixty-one patients thymoma with MG, as confirmed by postoperative histology, who underwent by VATS in Department of Thoracic Surgery - Military Hospital 103, Vietnam from 10/2013 to 5/2019 were included 2.1.1 Selection criteria + Patients diagnosed before surgery: thymoma with MG + MG class I and IIA + Treatment by VATS for thymoma and thymectomy + Having histopathological results post-surgery to confirm thymoma + No age limit, regardless of gender + Patients and their families were clearly explained about the disease, VATS and voluntary participation in research + There are sufficient medical records (the medical records must meet the requirements of the study) 2.1.2 Exclusion criteria + Recurrent thymoma + No indication for VATS: thymoma after radiotherapy, invasion into large blood vessels, lung hilum, trachea + Loss or incomplete medical records according to research requirements 2.2 Methods 2.2.1 Study design: intervention, no comparison, and prospective descriptive study, convenient sample size 2.2.2 Research facilities Chest endoscopy system, Electric cautherization system, harmonic scalpal, Automatic cutting-stitching tool, Trocards for VATS, Other endoscopic tools 2.2.3 Surgical procedure 2.2.3.1 Indication + MG class I, IIA + Thymoma: size < 10 cm, non-invasive into great vessels, lung hilum, trachea 2.2.3.2 Pre-operative * MG diagnosis: + Ptosis, muscle weakness changes during the day + Test Prostigmin: positive + Electromyography: positive * Pre-operative medical treatment: + Checking, preventing and treating the infection + Raising MG class, stabilizing MG condition * Explain carefully to patients and families 2.2.3.3 Techniques of VATS thymectomy * Anaesthetize: with a double-lumen endotracheal tube * Position: 30-45 degree lateral position * Surgery technique:: Follow rules: - VATS, if not successful, can be converted to supportedVATS, small mamary incision or conversion to open surgery - Remove the entire thymic tumor, thymus gland, and mediastinal fat from under the pericardium to the base of the neck, between the right and left diaphragm nerves - Surgical approach: via the left or right pleural cavity was determined according to the position of the thymoma presented in the pre-operative diagnosis by chest CT, use trocards - Determination of mediastinal pleura and anatomical landmarks; removal of thymic tumors and thymus gland - Take the specimen with a specimen endo-bag under the camera's observation - Re-check the surgical area and remove the VATS instruments 2.4.4 Post-operative treatment - After surgery, withdraw the endotracheal tube and transfer to the Department of Thoracic Surgery or the intensive care unit (ICU) - Monitor the chest tube drainage - Continue medicine treatment for MG - Post-operative X-ray -Chest tube extubation: lung expands well, no pneumothorax, pleural effusion < 100ml/24h - Re-examine by X-ray after the chest tube drainage extubation - Checking the surgical wounds - Monitor and manage postoperative complications - Combined treatments after surgery 11 Table 3.10 Characteristics of thymoma on chest CT Characteristics Patients Rate (%) Right 21 34,4 Left 17 27,9 Centre 23 37,7 < cm 17 27,9 3-6 cm 35 57,4 ≥ cm 14,7 Round 35 57,4 Oval 23 37,7 Plaque 4,9 Smooth 42 68,9 Irregular 19 31,1 Low 0 Medium 43 70,5 High 18 29,5 The extent of Less 8,2 contrast Medium 26 42,6 absorption Much 30 49,2 Yes 6,6 No 57 93,4 Yes 16 26,2 No 45 73,8 Yes 1,6 No 60 98,4 Position Size Shape Coutour Degree of enhancement Calcification Invasion Necrosis Table 3.11 Characteristics of thymoma on MRI 12 Patient Characteristics Rate (%) (n = 27) Round, oval 24 88,9 Other 11,1 Smooth 15 55,6 Lobular 12 44,4 Fiber Yes 24 88,9 encapsulate No 11,1 Yes 14 51,9 No 13 48,1 Yes 18,5 No 22 81,5 Shape Contour Fiber septum Invasion Size Length (mm) 35,30 ± 13,92 Width (mm) 23,93 ± 13,39 CSR= 1,04 ± 0,17 Table 3.12 Histopathology and size of thymoma on chest CT Mean largest diameter Type Patients Rate (%) A 11 18 33,73 ± 11,94 AB 18 29,5 39,94 ± 21,16 B1 13 21,3 41,00 ± 17,50 B2 18 29,5 46,22 ± 19,37 B3 1,7 37 Total 61 100 40,85  18,34 (mm) (  SD) 3.3 Results of VATS for thymoma with MG at Military Hospital 103 3.3.2 Characteristics of technique of VATS for thymoma with MG 13 Table 3.24 Access to mediastinum via pleural cavity Access to mediastinum Patients Rate (%) Right pleural cavity 35 57,4 Left pleural cavity 26 42,6 Total 61 100 Table 3.25 Number of trocards Trocards Patients Rate (%) 59 96,7 3,3 Total 61 100 Table 3.26 Position of ports Position of ports Patients Rate (%) ICS - AAL 37 60,7 Trocard ICS – MAL 6,6 ICS – AAL 16 26,2 ICS - MAL 6,6 ICS – AAL 21 34,4 Trocard ICS - MAL 34 55,7 ICS – AAL 4,9 ICS - MAL 4,9 ICS – AAL 9,8 Trocard ICS – MCL 52 85,2 ICS – AAL 1,6 ICS – MCL 3,3 ICS - MCL 3,3 Trocard 14 Table 3.31 Surgery method in relation of Masaoka’s staging Masaoka’s staging Surgery method Total I II III IVa n 34 11 53 % 64,2 20,8 13,2 1,9 100 Conversion to n 1 open surgery % 12,5 12,5 75,0 100 n 41 12 10 61 % 57,4 18,0 13,1 11,5 100 VATS Total p < 0,001b 3.3.3 Efficacy of VATS for thymoma with MG Table 3.33 Surgical time Surgical time (minutes) Patients Rate (%) ≤ 60 23 37,7 > 60 - 120 27 44,3 > 120 11 18,0 Total 61 100 Mean surgical time (min) (  SD) 91,80  49,94 Mean blood loss volume (ml) (  SD) 37,38  31,58 Table 3.37 Length of ICU Length of ICU stay Corrected Patients Rate (%) None 42 68,9 68,9 ≤ 24 15 24,6 93,5 > 24 – 48 3,3 96,8 (hours) rate (%) 15 > 48 3,3 Total 61 100 100 ≤ 24 (93,5%) Table 3.38 Chest tube removal time Chest tube removal time Corrected rate Patients Rate (%) ≤ 24 3,3 3,3 > 24 – 48 40 65,6 68,9 > 48 19 31,1 100 Total 61 100 (hours) (%) Mean of chest tube removal time (hours) (  SD): 57,84  30,71 ≤ 48 giờ: 68,9% Table 3.39 Complications Complications Patients Rate (%) Respiratory distress 11,5 Pleural effusion 1,6 Total 13,1 Table 3.40 Postoperative hospital stay (days) Postoperative hospital Cumulative Patients Rate (%) ≤7 28 45,9 45,9 – 10 21 34,4 80,3 > 10 12 19,7 100 Total 61 100 stay (days) rate (%) Mean of Postoperative hospital stay (days) (  SD): 9,8  5,9 3.3.4 Results VATS for thymoma with MG 16 Table 3.41 Change the MG status at times Monitor time MG status after surgery After After After surgery: surgery: surgery: month month > year (n=61) (n=58) (n=53) n % n % n % Complete stable remission 11,5 15,5 12 22,6 Improved 45 73,8 72,4 38 71,7 Unchanged 14,8 12,1 5,7 Worse 0 0 0 Died of MG 0 0 0 The longer the monitoring period, the higher the complete stable remission and improved rate Table 3.42 Recurrence tumor after surgery at times Follow time Recurrence tumor After After surgery surgery month month (n=61) (n=58) After surgery Over year (n=53) n % n % n % Recurrence 0 0 3,8 None 61 100 58 100 51 96,2 17 Total 61 100 58 100 53 100 02 recurrence tumor after surgery over year CHAPTER 4: DISCUSSION 4.2 Characteristics of clinical, imaging and histopathology of thymoma with Myasthenia Gravis which performed by VATS 4.2.1 Characteristics of clinical of thymoma with MG which performed by VATS The most common symptom is ptosis (71,2%) There were one or more clinical symptoms in one patient * MG status of thymoma patient There were 80.3% of MG class IIA Patients in class IIB or higher levels were not indicated for surgery because there were many complications after surgery, especially respiratory failure 4.2.2 Imaging of thymoma with MG which performed by VATS 4.2.2.1 Characteristics of thymoma with MG on chest CT * Tumor location: thymus tumors were found in any location Tumor located in different locations was found by McErlean In this study, thymoma was located in all positions, left site: 27.9%, right site: 34.4% and in the central position was 37.7% * Tumor size: 85% of the tumors are under cm, most tumors are from 3-6cm: 57.4% * Tumor shape: round and oval are common (95.1%) * Tumor contour: smooth and irregular were 68.9% and 31.1%, respectively * Tumor density: medium or high level 18 * Extent of contrast absorption: the degree of contrast absorption more or less reflects the level of malignancy We only had cases (8.2%) with low contrast absorption According to Pham Huu Lu, there is no relationship between the degree of contrast absorption and the malignant properties of thymoma * Calcification, invasion and necrosis of tumors: the rate of invasion observed on CT was quite high, up to 26.2%, meanwhile the rate of calcification and necrosis is low (6.6% and 1.6 %) 4.2.2.2 Characteristics of thymoma with MG on MRI * Shape of the thymoma on MRI There were 24/27 thymoma cases (88.9%) were round or oval, 15 were smooth (55.6%) Mai Van Vien's study on 188 operated-patients with MG, there was one case of thymus carcinoma In this study, there were 24 thymoma cases (88.9%) with partial or complete fibrous encapsulation There were 13 tumors (48.1%) with fibrous septa The thymic tumor has a mean size of 35.30 ± 13.92mm in length, 23.93 ± 13.39mm in width * CSR index: The average CSR was 1.04 ± 0.17 Phung Anh Tuan concluded that CSR values can be used to distinguish between thymoma and non-thymoma cases The authors Inaoka T, Popa G, Priola AM found that the difference of CSR between hyperplastic patients and thymoma patients was statistically significant with p