Is surgical resection justified for myasthenia gravis? Long-term results in over 1000 cases.Andrew J. Kaufman, MD; Justin Palatt, MD; Mark Sivak, MD, Peter Raimondi,

BS, Dong-Seok Lee, MD; Andrea Wolf, MD, MPH; Fouad Lajam, MD, Faiz Bhora, MD; Raja M. Flores MD.

Department of Thoracic Surgery, Mount Sinai School of Medicine

Andrew J. Kaufman MDAssistant Professor, Thoracic Surgery

Mount Sinai School of MedicineChief, Thoracic Surgery Mount Sinai Beth Israel

New York, New York

Disclosures

None

Background• Myasthenia gravis (MG) is a rare autoimmune disease

• Prevalence 0.5 to 20.5 per 100,000• Symptoms: Ocular, bulbar, and generalized • Frequently causes severe disability in those affected• Uncommonly fatal

• Treatment: • 1930’s Anticholinesterases• 1950’s Immunosuppressants• 1970’s Plasma exchange (PLEX) and IVIG• 1913, 1939-1945 Thymectomy introduced

• Role of thymectomy remains controversial• AAN recommendation as “Optional”1.

1Gronseth GS, Barohn RJ. Neurology 2000;55:7-15

Goal of Study• Evaluate the role of thymectomy in the treatment of MG.

• Focus of Study:• Long-term outcomes • Appropriate statistical analysis

• Endpoints:• Accurately determine rate of complete stable remission

(CSR)• Determine if surgical technique affects rate of CSR• Describe patient characteristics affecting rate of CSR

Methods• Retrospective review of a prospectively maintained

database of thymectomy patients from 1941-2013. • 1002 included in study.• Inclusion Criteria:

• Thymectomy• Age at time of surgery• Gender • Duration of symptoms before surgery• Osserman Classification before and after surgery• Surgical technique• Presence of thymoma• Date of remission, and status at last follow-up

Methods

• Statistical design: Complete stable remission and patient variables were analyzed:• Chi squared• Wilcoxin signed-rank test• Crude rate percentage• Interval-censored Kaplan-Meier Estimate• Interval-censored Cox proportional hazards model

Methods• Definitions:

• Complete Stable Remission: asymptomatic off all medications for 1 year postoperatively.

• Modified Osserman Classification:• Class I: ocular• Class II: mild generalized/bulbar weakness• Class III: moderate generalized/bulbar weakness• Class IV: severe generalized weakness or respiratory

dysfunction or both.

Surgical Technique• Thymectomy consisted of removal of all thymic tissue

including cervical poles and standard resection of mediastinal fat between the phrenic nerves, from thyroid to diaphragm. Using 4 approaches:

• Transcervical : no sternal split• Trans-sternal: no formal neck dissection• Thoracotomy• VATS

Results: Patient CharacteristicsTotal

N = 1002

Complete Stable Remission

N = 191

No Remission

N = 811p -value

Years follow-up median (IQR)

6.0 (1-10) 9.0 (7-12) 4.0 (1-10) <.0001

Age at time of thymectomy, mean in years (SD)

40.8 (17.4) 37.2 (16.5) 41.7 (17.5) 0.0012

Gender (N,%)

Male 350 (34.9%) 67 (35.1%) 283 (34.9%) 0.9619

Female 652 (65.1%) 124 (64.9%) 528 (65.1%)

Years from Dx to thymectomy, Median (IQR)

1.0 (0-3) 1.0 (0-3) 1.0 (0-3) 0.3708

Results: Patient CharacteristicsTotal

N = 1002

Complete Stable

RemissionN = 191

No Remission

N = 811p -value

Preop Osserman (N,%)

Class I 74 (7.4%) 12 (6.3) 62 (7.6%)

Class II 777 (77.5%) 159 (83.2%) 618 (76.3%) 0.1068

Class III 118 (11.8%) 18 (9.4%) 100 (12.3)

Class IV 33 (3.3%) 2 (1.1%) 31 (3.8%)

Presence of Thymoma (N,%)

Yes 163 (16.3%) 13 (6.8%) 150 (18.5%)

No 893 (83.7%) 178 (93.2%) 661 (81.5%) <.0001

Results: Patient Characteristics

TotalN = 1002

Complete Stable

RemissionN = 191

No Remission

N = 811p -value

Surgical Technique (N,%)

Transcervical 744 (74.25%) 158 (82.7%) 586 (72.3%)

Trans-sternal 199 (19.86%) 25 (13.1%) 174 (21.5%)

Thoracotomy 43 (4.29%) 6 (3.1%) 37 (4.5%)

VATS 16 (1.6%) 2 (1.1%) 14 (1.7%) 0.0306

Crude Rate Results

Category of Response Number of Patients Percent of Patients

Complete Stable Remission 191/1002 19%

Improvement 164/1002 16.3%

Stable 580/1002 58%

Progression 67/1002 6.7%

Interval-censored Kaplan-Meier estimate of time to complete stable remission

0 10 20 30 40 50

Time

0.0

0.1

0.2

0.3

0.4

0.5

Failu

re P

roba

bilit

y

Time to Remission in years

Cu

mu

lati

ve P

rob

ab

ility

of

CS

R

Time Interval in Years Estimate of CSR Estimate of Non-CSR Standard Error0-2 15.99% 84.01% 1.42%3-7 19.39% 80.61% 1.49%8-8 19.43% 80.57% 1.49%9-10 27.68% 72.32% 1.72%11-15 29.14% 70.86% 1.74%16-24 32.17% 67.83% 1.89%25-39 36.65% 63.35% 2.25%40-50 47.31% 52.69% 8.98%

Multivariate Cox ModelChi Square P-value

Hazard Ratio of CSR

95% CI

Age at time of Surgery 0.0556 0.8136 1.001 0.992-1.011

Gender 0.9417 0.3318 1.172 0.851-1.615

Duration of Symptoms 3.3609 0.0668 0.971 0.942-1.002

Presence of Thymoma 7.473 0.0063 0.408 0.215-0.776

Preop Osserman

Class I Ref

Class II 1.0597 0.3033 0.725 0.393-1.377

Class III 4.6121 0.0317 0.432 0.200-0.929

Class IV 5.6645 0.0173 0.157 0.031-0.721

Surgical Technique

Transcervical Ref

Trans-sternal 5.7379 0.016 0.577 0.345-0.899

Thoracotomy 0.0644 0.7997 1.124 0.455-2.775

VATS 1.8899 0.1692 2.744 0.651-11.56

Key Points• Our Study, is the largest single-center retrospective

study of thymectomy patients to date, and reports long-term outcomes.

• Thymectomy associated with high rate of CSR: 47.3% maximal rate.• CSR rates increase steadily over time• Crude rate underestimates CSR

• Thymoma decreased the likelihood of CSR.• Trans-sternal thymectomy lower probability of CSR• Osserman Classification III and IV patients fared worse.

Limitations of the Study• Retrospective• Long time span of the study• Did not use MGFA Classification of symptoms• Lack specific data:

• Antibody status (AchR-ab, MUSK)• Histology• WHO classification and Masaoka Staging of

thymomas• Medication regimen and dosing not accounted for

Conclusions

• Thymectomy is associated with a high rate of complete stable remission

• Thymectomy should be recommended for patients with myasthenia gravis

• Especially those with nonthymomatous myasthenia and mild symptoms

Acknowledgements

• Joan Bratton• Department of Neurology• Icahn School of Medicine at Mount Sinai

• Emilia Bagiella PhD and Evie Andreopoulos• Director, Center for Biostatistics• Department of Population and Health Sciences• Icahn School of Medicine at Mount Sinai

Thank You

Discussion