VIETNAM MILITARY MEDICAL UNIVERSITYLE VIET ANH STUDY ON APPLICATION OF VIDEO-ASSISTED THORACOSCOPIC SURGERY FOR THYMOMA WITH MYASTHENIA GRAVIS AT MILITARY HOSPITAL 103 Specialized: Surg
Trang 1VIETNAM MILITARY MEDICAL UNIVERSITY
LE VIET ANH
STUDY ON APPLICATION OF VIDEO-ASSISTED THORACOSCOPIC SURGERY FOR THYMOMA WITH MYASTHENIA GRAVIS
AT MILITARY HOSPITAL 103
Specialized: SurgeryCode: 9720104
SUMMARY OF DOCTORAL THESIS
HANOI – 2019
Trang 2Scientific 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:
1 The National Library
2 Military Medical University Library
Trang 31 AAL Anterior axillary line
2 CSR Chemical shift ratio
4 MRI Magnetic resonance imaging
5 MAL Mid-axillary line
6 MCL Midclavicular line
8 ICU Intensive care unit
9 ICS Intercostal space
10 VATS video-assisted thoracoscopic surgery
INTRODUCTION
Thymoma is a rare epithelial tumor of the thymus but the mostcommon mediastinal tumor in adults, accounting for 15% -21.7% ofmediastinal tumors and 47% of anterior mediastinum tumors, about0.2% -1.5% of all malignant tumors
Research by Strollo DC (1997) shows that thymoma iscommon in adults, Myasthenia Gravis (MG) occurs in approximately30% to 50% of patients with thymoma In comparison, only 15% ofpatients with MG have a thymoma MG is also known as anautoimmune disease that is related to the thymus's activity andpathological disorders
The diagnosis of thymoma with MG plays an important role.There are many diagnostic methods, the most common is chestcomputerized tomography (CT) and magnetic resonance imaging(MRI)
Trang 4Many authors have affirmed that when a thymoma with MGwas a diagnosis, thymectomy is a first-choice treatment and mosteffective However, the results also depend on many factors such aspre-operative patient's status, surgical method, postoperativetreatment…
Up to date, there are many methods for surgery to removethymoma and thymus, such as trans-sternal, transcervical,thoracotomy approach, especially Minimal invasive surgery: video-assisted 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 severepain, easily affected by respiratory function, or having sternitiescomplications Transcervical surgery is difficult to remove all thethymoma and thymus gland, especially in cases of thymoma andthymus enlargement, located at the lower pole The VATS isconsidered by many authors to have many advantages: less pain, lessimpact on respiration, early recovery
With many years of treatment of MG, thymoma, and morethan 10 years of experience in VATS, Department of ThoracicSurgery - Military Hospital 103 has made initial success in treatmentthymoma with MG by VATS However, the question is whether theVATS for treating thymoma with MG will completely removethymoma, thymus and mediastinal fat as well as open surgery andhow 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
Trang 5Therefore, stemming from practical demands mentioned
above, we carried out the thesis: " Study on application of assisted thoracoscopic surgery for thymoma with Myasthenia Gravis at Military Hospital 103" with two purposes:
video-1 Review some clinical, imaging and histopathological
characteristics of thymoma with Myasthenia Gravis performed
by VATS.
2 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 1 year, MG class I and IIA
The thesis has described some features of imaging,histopathology of thymoma with myasthenia gravis at MilitaryHospital 103 with CT imaging: thymoma are located in every position,round or oval shape, the high degree of enhancement and level of drugabsorbed 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 thymuscarcinoma; the largest size is type B2 and the smallest size is type A The thesis has shown that the effectiveness of VATS fortreatment thymoma with myasthenia gravis at Military Hospital 103with a complete cure rate and improved after surgery increases withfollow-up time: 1 month: 85.3%, 6 months: 87.9%,> 1 year: 94.3%
The composition of the thesis:
The thesis has 132 pages Introduction: 2 pages; Overview: 32pages; Objects and methods: 27 pages; Results: 32 pages; Discussion: 36
Trang 6pages; 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
- 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
Trang 7thymus and thymoma The authors calculated the chemical shift ratio(CSR - chemical shift ratio) CSR is statistically significant indistinguishing 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 involvementbut no pulmonary involvement
+ Class IIB: moderately generalized MG: bulbar manifestations.+ Class III: rapid progression of generalized bulbar disease andweakening 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 encapsulatedtumor
+ Stage II: Macroscopic invasion into thymic or surrounding fattytissue, or mediastinal pleura or pericardium and microscopic trans-capsular 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 toremove all of the thymoma, the thymus, and the mediastinal fat
Trang 81.3.2 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 RayHospital 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 bypostoperative histology, who underwent by VATS in Department ofThoracic Surgery - Military Hospital 103, Vietnam from 10/2013 to5/2019 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 mustmeet the requirements of the study)
2.1.2 Exclusion criteria
+ Recurrent thymoma
Trang 9+ No indication for VATS: thymoma after radiotherapy, invasion intolarge blood vessels, lung hilum, trachea.
+ Loss or incomplete medical records according to researchrequirements
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 forVATS, Other endoscopic tools
+ 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.
Trang 10- Surgical approach: via the left or right pleural cavity wasdetermined according to the position of the thymoma presented in thepre-operative diagnosis by chest CT, use 3 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'sobservation
- 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 theDepartment 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, pleuraleffusion < 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
Trang 112.2.5 Monitor and evaluate the long-term results
* Monitor: 1 month, 6 months and over 1 year post-surgery
* Basis for evaluating results:
+ The progression of symptoms of MG, demand for medication aftersurgery
+ Tumor recurrence: by chest CT
+ Working quality of patients after surgery
+ Quality of life after surgery
* Methods of monitoring:
+ Direct examination
+ Phone, use post-surgery test slip sent to each patient
+ Receiving chest CT scan results from the patients
- Sites, number of ports, the position of the port
- Surgey method: VATS and conversion to open surgery
- Operative evaluations: the number and position of the tumor, tumorsize, the status and extent of the invasion, complications, surgicaltime, volume of blood lost
Trang 122.2.6.4 Post-Operative criteria
- Length of ICU stay
- Chest tube removal time
- Complications after surgery
- Post-operative hospital stay
- Histopathological results:
+ According to WHO in 2004
+ Determining the invasion status according to Masaoka’s staging
2.2.6.5 Indicators for long term monitoring after surgery
+ Assessing the recurrence tumor status: by CT
+ Assessing the improvement of MG: complete stable remission,improved, unchanged, worse, died of MG
2.2.7 Statistical analysis
Statistical data were analyzed using SPSS version 23.0
CHAPTER 3: RESULTS 3.1 General characteristics of the research subjects
- The average age of the patients was 47,31 ± 10,87 years
- Female/male ratio = 0,91
- Duration of disease was less than 1 years: 82%
3.2 Characteristics of clinical, imaging and histopathology of thymoma with MG performed by VATS.
Table 3.6 MG status before surgery
Trang 13Table 3.10 Characteristics of thymoma on chest CT
Characteristics Patients Rate (%)
Table 3.11 Characteristics of thymoma on MRI
Characteristics Patient Rate (%)
Trang 14(n = 27) Shape Round, oval
Other
243
88,911,1
Lobular
1512
55,644,4
Fiber
encapsulate
Yes No
243
88,911,1
Fiber septum Yes
No
1413
51,948,1
No
522
18,581,5
Width (mm)
35,30 ± 13,9223,93 ± 13,39CSR= 1,04 ± 0,17
Table 3.12 Histopathology and size of thymoma on chest CT
Type Patients Rate (%) Mean largest diameter
Trang 15Table 3.24 Access to mediastinum via pleural cavity
Access to mediastinum Patients Rate (%)
Table 3.25 Number of trocards
Table 3.26 Position of ports
Position of ports Patients Rate (%)
Trang 16Table 3.31 Surgery method in relation of Masaoka’s staging
Surgery method Masaoka’s staging Total p
3.3.3 Efficacy of VATS for thymoma with MG
Table 3.33 Surgical time
Surgical time (minutes) Patients Rate (%)
Table 3.37 Length of ICU
Length of ICU stay
(hours) Patients Rate (%)
Corrected rate (%)
Trang 17Total 61 100
≤ 24 giờ (93,5%)
Table 3.38 Chest tube removal time
Chest tube removal time
(hours) Patients Rate (%)
Corrected rate (%)
Mean of Postoperative hospital stay (days) ( SD): 9,8 5,9
3.3.4 Results VATS for thymoma with MG
Trang 18Table 3.41 Change the MG status at times
MG status after surgery
Monitor time After
surgery:
1 month (n=61)
After surgery:
6 month (n=58)
After surgery:
> 1 year (n=53)
surgery
1 month (n=61)
After surgery
6 month (n=58)
After surgery Over 1 year (n=53)
Trang 19CHAPTER 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 wereone or more clinical symptoms in one patient
* MG status of thymoma patient
There were 80.3% of MG class IIA Patients in class IIB orhigher levels were not indicated for surgery because there weremany 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 Tumorlocated 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 6 cm, most tumors arefrom 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
* Extent of contrast absorption: the degree of contrast absorptionmore or less reflects the level of malignancy We only had 5 cases(8.2%) with low contrast absorption According to Pham Huu Lu,
Trang 20there is no relationship between the degree of contrast absorption andthe malignant properties of thymoma.
* Calcification, invasion and necrosis of tumors: the rate of invasionobserved on CT was quite high, up to 26.2%, meanwhile the rate ofcalcification 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 oroval, 15 were smooth (55.6%) Mai Van Vien's study on 188operated-patients with MG, there was one case of thymus carcinoma
In this study, there were 24 thymoma cases (88.9%) with partial orcomplete fibrous encapsulation There were 13 tumors (48.1%) withfibrous 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 Tuanconcluded that CSR values can be used to distinguish betweenthymoma and non-thymoma cases The authors Inaoka T, Popa G,Priola AM found that the difference of CSR between hyperplasticpatients and thymoma patients was statistically significant with p
<0.001
4.2.3 Histopathology of thymoma with MG performed by VATS
Type AB and type B2 type were the highest rates (29.5%),with no thymic carcinoma The type B2 has the largest size (46,22 ±19,37 mm), the smallest size was in type A (33,73 ± 11,94 mm)
There is no difference between the sizes of thymic tumortypes Therefore, the size of the thymoma has little prognostic value
4.3 Results of VATS for treating thymoma with MG at Military Hospital 103