Surgical approaches for stage Ⅰ and Ⅱ thymoma-associated myasthenia gravis:feasibility of complete video-assisted thoracoscopic surgery (VATS) thymectomy in comparison with trans-sternal resection

Complete resection could be achieved in virtually all myasthenic patients with Masaoka stage I and II thymoma us- ing the trans-sternal technique. Whether this is appropriate for minimally invasive approach is not yet clear. We evalu- ated the feasibility of complete video-assisted thoracoscopic surgery （VATS） thymectomy for the treatment of Ma- saoka stage I and Ⅱ thymoma-associated myasthenia gravis, compared to conventional trans-sternal thymectomy. We summarized 33 patients with Masaoka stage I and II thymoma-associated myasthenia gravis between April 2006 and September 2011. Of these, 15 patients underwent right-sided complete VATS （the VATS group） by us- ing adjuvant pneuomomediastinum, comparing with 18 patients using the trans-sternal approach （the T3b group）. No intraoperative death was found and no VATS case required conversion to median sternotomy. Significant differences between the two groups regarding duration of surgery and volume of intraoperative blood loss （P = 0.001 and P 〈 0.001, respectively） were observed. Postoperative morbidities were 26.7% and 33.3% for the VATS and T3b groups, respectively. All 33 patients were followed up for 12 to 61 months in the study. The cumulative probabilities of reaching complete stable remission and effective rate were 26.7% （4/15） and 93.3% （14/15） in the VATS group, which had a significantly higher complete stable remission and effective rate than those in the T3b group （P = 0.026 and P = 0.000, respectively）. We conclude that VATS thymectomy utilizing adjuvant pneuomo- mediastinum for the treatment of stage I and II thymoma-associated myasthenia gravis is technically feasible but deserves further investigation in a large series with long-term follow-up.

Effectiveness of Thymectomy in Non-thymomatous Myasthenia Gravis: a Systematic Review

There is continuous debate regarding the effectiveness of thymectomy in the treatment of non-thymomatous myasthenia gravis （MG）. This systematic review was undertaken to determine whether thymectomy was effective in non-thymomatous MG. We retrieved articles published between January 1980 and September 2013. Sixteen cohort studies were included. Given the considerable het- erogeneity, we used a descriptive method instead of statistical synthesis. The median relative rates （RRs） and their interquartile ranges were used to estimate the magnitude of benefit. Compared to conserva- tively treated MG patients, thymectomized patients had higher survival, clinical remission, pharma- cologic remission and improvement rates, and RRs were 1.07 （1.01-1.17）, 1.83 （0.82-2.99）, 1.55 （1.22-1.95） and 1 （1.00-1.09）, respectively. Subgroup analyses showed that patients with moderate to severe generalized MG benefited more from thymeetomy, with RRs of survival and pharmacologic re- mission increasing to 1.35 （1.24-1.49） and 2.68 （1.73-4.17）, respectively. These results suggested that thymectomy might be an effective procedure in non-thymomatous MG patients. The patients with mod- erate to severe generalized MG might benefit more. Taking into account the poor methodological qual- ity of present studies, more well-designed prospective randomized controlled trials （RCTs） are still re- quired to reach uneouivocal conclusion.

The Influence of Thymectomy on Germ-cells of the Testis in Mice

We performed thymectomy on the immature and mature male mice and made a quantitative assay of various germ cells of tbe seminiferous epithelium in the testis with Image Analyser System 35 days following thymectomy. The results indicated that as compared with the control group, all germ cells of the spermatogenesis lineage decreased in the immature group and in the mature group after thymectomy.The present study showed that thymus and its hormone stimulated not only the mitotic division, but also the meiotic division of germ cells during spermatogenesis, suggesting that thymus-sexual axis may play an important role in the process of spermatogensis in the testis.

Effect of thymectomy for 36 children with myasthenia gravis

objective: To analyze the effects of thymectomy for children with myasthenia gravis (MG).Methods: Thirty-six children with MG were treated by thymectomy from 1984 to 1997, their age ranging from 4 to 14 years, with symptom duration from 2 months to 8 years. According to Osserman’s classifica tion, 27 case belongs to class Ⅰ, 6 class Ⅱa, 2 class Ⅱb and 1 class Ⅲ. The outcome was graded as "much im proved", "improved", "unchanged" and "deteriorated or death". Results: 13. 9% of patients were much im proved, 69. 4% improved, so the better response to thymectomy (much improved or improved) is 83. 3%, which is significantly higher than the control group (without surgical treatment) 44. 8% (P<0. 001), and no one exacerbated or died. Conclusion: Thymectomy for children with MG is safe and effective, and the out come after thymectomy relates to the duration of symptoms and pathologic classification, but irrelevant to sex and age, and the follow-up results were satisfactory.

Robotic–Assisted Thymectomy in Patients with Nonthymomatous Myasthenia Gravis

Complete removal of the thymus and fatty tissue adherent to pericardium is crucial for treating myasthenia gravis. Our aim was to analyze our surgical and clinical results and early experience of robot-assisted thy-mectomy in patients with nonthymomatous myasthenia gravis. Between January 2008 and October 2010, 8 patients, all women, with nonthymomatous myasthenia gravis underwent robot-assisted thymectomy using a 3-port, left-sided approach. There were no operative mortality;1 patient had left phrenic nerve injury. Com-plete remission was achieved in 25% of the patients at 18 months’ follow-up. There was no significant agreement between preoperative computed tomography and histopathology finding (kappa = 0.059;P = 0.85) and no significant correlation between age and duration of symptoms (P = 0.51). Robotic-assisted thymec-tomy is promising procedure. It can be performed safely and effectively. With follow-up greater than 12 months, 87.5% of the patients who underwent robot-assisted thymectomy demonstrated clinical improve-ment.

Perioperative and long-term outcome of thymectomy for myasthenia gravis： comparison of surgical approaches and prognostic analysis

Background Thymectomy is an established treatment for myasthenia gravis （MG）, and video-assisted thoracoscopic surgery （VATS） thymectomy has become an acceptable surgical procedure. This study aimed to compare the results of VATS thymectomy and open thymectomy and to identify the prognostic factors after thymectomy. Methods The clinical data of 187 consecutive thymectomies performed between July 2000 and December 2009 were retrospectively reviewed; 75 open thymectomies and 112 VATS thymectomies. Clinical efficacy and variables influencing outcome were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Results The operative blood loss in the VATS group was significantly less than that in the open group （（62.14＋55.43） ml vs. （137.87＋165.25） ml, P 〈0.05）. The postoperative crisis rate increased with the severity of preoperative MG and the prescription dose of anticholinesterase. Complete follow-up information of patients more than 12 months after the thymectomy was obtained on 151 cases, 89 cases from the VATS group and 62 cases from the open group, with a mean follow-up period of 59.3 months, range from 12 to 117 months. Complete stable remission （CSR） was the end point for evaluation of the treatment results. The overall five-year CSR rate was 57.5%. Two good prognostic factors were identified; preoperative prescription of anticholinesterase alone （P=0.035） and non-thymomatous MG （P=0.003）. The five-year CSR rate of the ocular type of MG reached a high level of 67.4%. Conclusions Thymectomy can achieve good long-term CSR in MG, and VATS is an ideal alternative method. High-dose prescription of anticholinesterase and the advanced stage by Myasthenia Gravis Foundation of America （MGFA） classification have higher risks of postoperative crisis. Preoperative prescription of anticholinesterase alone and non-thymomatous MG are good prognostic factors. Thymectomy should also be considered for the ocular tvioe of MG.

Predictors of postoperative myasthenic crisis in patients with myasthenia gravis after thymectomy

Background Thymectomy is considered the most effective treatment in patients with myasthenia gravis. This study aimed to explore the predictors of postoperative myasthenic crisis in patients with myasthenia gravis after thymectomy.Methods Clinical records of 243 patients with myasthenia gravis who underwent thymectomy were reviewed retrospectively. The following factors were analyzed in relation to the occurrence of myasthenic crisis after thymectomy：gender, age, duration of symptoms, Osserman stage, history of myasthenic crisis, concomitant diseases, preoperative pyridostigmine dose, preoperative steroid therapy, operation approach, operation time, presence of thymoma, major postoperative complications.Results Forty-four patients experienced postoperative myasthenic crisis during the first month after thymectomy.Univariate analysis revealed that Osserman stage （RR=0.0976, P=0.000）, history of myasthenic crisis （RR=0.2309,P=0.012）, preoperative pyridostigmine dose （RR=0.4349, P=0.016）, thymoma （RR=0.0606, P=0.000）, and major postoperative complications （RR=0.1094, P=0.000） were significantly related to postoperative myasthenic crisis.Multivariate Logistic regression analysis showed that Osserman stage （Ⅱb＋Ⅲ＋Ⅳ） （RR=0.0953, P=0.000）, thymoma （RR=0.0294, P=0.000）, and major postoperative complications （RR=0.0424, P=0.000） independently predict postoperative myasthenic crisis.Conclusion Osserman stage （Ⅱb＋Ⅲb＋Ⅳ）, thymoma and major postoperative complications are independent predictors of postoperative myasthenic crisis in patients with myasthenia gravis who underwent thymectomy.

Value of Adjuvant Radiotherapy for Thymoma with Myasthenia Gravis after Extended Thymectomy

Background：The co-existence of myasthenia gravis （MG） and thymoma makes the surgical treatment more complicated and adjuvant radiation more controversial. The aim of this study was to investigate adjuvant radiotherapy for thymoma with MG after extended thymectomy.Methods：A total of 181 patients with both MG and thymoma were recruited between 2003 and 2014 at Tongren Hospital, China. Among all the patients, 157 patients received radiation therapy after surgery （Group A）; whereas the other 24 patients did not receive radiation therapy （Group B）. According to the time that patients started mediastinal radiation therapy, we subdivided the 157 patients in Group A into subgroups （1-month subgroup, n = 98; 2-month subgroup, n = 7; and 3-month subgroup, n = 52）. We then compared the effect of the mediastinal radiation therapy across these different groups using the survival rate, the rate of postoperative myasthenic crisis, and the complete stable remission （CSR） rate as the primary endpoints.Results：There was a significant difference in the occurrence of postoperative myasthenic crisis between 1-month subgroup and Group B （χ2 = 4.631, P = 0.031）. The rates of reaching CSR were 32.6% in 1-month subgroup, 25% in 3-month subgroup, and 22.7% in Group B, respectively. The overall survival rates of 1-month subgroup, 3-month subgroup, and Group B were 88.8%, 83.3%, and 77.3%, respectively. Analysis on the Kaplan-Meier survival curves demonstrated that within 8 years after surgery, there was no significant difference in aspects of overall survival and disease-free survival between 1-month subgroup and Group B, and between 3-month subgroup and Group B; over 8 years after surgery, the disease-free survival rates in 1-month subgroup, 3-month subgroup and Group B were 79.4%, 70.6%, and 55.3%, respectively.Conclusions：Adjuvant radiation within 1 month after extended thymectomy may be helpful in controlling postoperative MG, such as decreasing the possibility of postoperative myasthenic crisis, and raising cumulative probabilities of reaching CSR.

An improved method for rat intubation and thymectomy

Background Thymokidney has been reported as an approach for a vascularized thymus for transplantation to induce donor specific tolerance. A completely thymectomized model which ensures that the obtained thymus is not injured has not been developed yet and it would be useful for evaluating autologous thymokidney function in rats. Methods Adult Sprague-Dawley male rats weighing 150-300 g （n=30） underwent non-invasive intubation with the assistance of an improved self-made wedge-shaped cannula made from a 2-ml plastic syringe and transillumination from the anterior tracheal area by an operation spotlight. The rats then received a thoracotomy while their breathing was supported by a small animal ventilator, and both lobes of the thymus were entirely extirpated under a 10x microscope. The postoperative survival rate of the rats was recorded, and changes in the T-cell reservoir from 9 of 30 rats within 21 days after surgery were monitored using flow cytometry. The complete thymectomy rate was confirmed by autopsy and histological examination on 21 days post-operation. Results The postoperative survival rate of rats was 100%. The exsected thymus was free of injury and the rate of complete thymectomy was 100%. Conclusions This model has a stable survival rate and complete thymectomy is able to be achieved. The obtained thymus tissue is free of injury and can be used for transplantation.

FACTORS RELATED TO LONG-TERM EFFEGTS OF THYMECTOMY ON MY ASTHENIA GRAVIS

The authors report the results of long-term follow-up after thymectomy on 92 cases with myasthenia gravis (MG), including 22 cases of thymomatous MG. These patients were followed up for 6-73 months with an average of 23 months. The surgically effective rate was 88.0% and the late mortality, 6.5%. The sex of the patients and the durations of disease were not obviously related to the prognosis, however the effect of thymectomy was much better in patients aged 10-39 years than in other age groups. The modified Osserman's clinical classification, acetylcholine receptor (AchR) antibodies and citric acid extract (CAE) antibodies titers in plasma and pathological patterns of the surgical specimens of thymus including immunohistochemical observation play an important role among larious factors related to the long-term effects.

The long-term outcome of thymectomy combined with steroid therapy for 52 myasthenia gravis patients with thymoma

Abstract Objective To evaluate the long term outcome of thymectomy combined with steroid therapy for myasthenia gravis (MG) with thymoma. Methods Fifty-two MG patients with thymoma (35 males, 17 females) treated with thymectomy combined with steroid therapy underwent a retrospective study during a follow up period of 1 to 20 years (mean 4.5±3.6) after thymectomy in order to evaluate the long term effective rate and survival rate. Five cases had ocular MG, and 47 had generalized MG (90.3%). The patients at onset from 8 to 61 years (mean 38.5±12.7). All patients were given steroid therapy before and after thymectomy. At the start of therapy, prednisone was given 30 mg to 60 mg daily. This dose was maintained until obvious improvement was found, after which prednisone dosage was gradually tapered to 10 mg to 20 mg daily as a maintenance dose and continued for 1 to 2 years. In all these patients the extended thymectomy was performed by median sternotomy, if possible, a complete resection of the thymoma and the thymic gland, including perithymic fat tissue was given. The survival rate after thymectomy was calculated employing the Kaplan Meier's method. Results The long term effective rate was 88.5% (46/52). In the 46 survivors, 8 of them (15.4%) Department of Neurology, Affiliated Hospital of Qingdao Medical College, Qingdao 266003, China (Cong ZQ, Wan SL, Wang HP and Yuan XY) Present address of Dr. Wan SL: The First Qing Dao Sanatorium of Jinan Military Region, PLA. China. obtained complete remission (patients asymptomatic without any therapy for at least 6 months), 29 of them (55.8%) had pharmacological remission (patients asymptomatic still on low dose corticosteroids or anticholinesterases), 9 of them (17.3%) had marked improvement (stable improvement of myasthenic signs corresponding to a decrease of 2 points on the functional scale of Oosterhuis et al). Six patients (11.5%) died during the observation period. Two of them died in one year after thymectomy; 4 of them died during the follow up period in from 1 to 20 years. The causes of death after surgery were: thymoma relapse and metastasis in 2 patients, heart failure after operation in 1, myocardial infarction in 1, myasthenic crisis in 1 and digestive tract hemorrhage due to high dose steroid in 1. The mortality of patients with invasive thymoma was 23% (3/13); the mortality of patients with noninvasive thymoma was 7.7% (3/39). The 1 year survival rate after operation was 96.2% (50/52), 3 year survival rate 91.4% (32/35), the overall 5 year survival rate 85.7% (18/21), the overall 7 year survival rate 77.8% (14/18) and the overall 10 year survival rate 33.3% (3/9). Conclusions The long term therapeutic results of thymectomy combined with steroid therapy were good for myasthenia gravis patients with thymoma. Our retrospective study results showed that thyectomy combined with steroid therapy played an important role in decreasing mortality and increasing remission rate.

Intraoperative cardiogenic shock induced by refractory coronary artery spasm in a patient with myasthenia gravis: A case report

BACKGROUND Coronary artery spasm(CAS)is a rare but critical condition during surgery.Clinical manifestations can vary from only subtle electrocardiography change to sudden death.In this case report,we present the case of a patient with myasthenia gravis(MG)who developed refractory CAS-related cardiogenic shock during thymoma surgery.CASE SUMMARY A 61-year-old man had a history of cigarette smoking and coronary artery disease with a bare metal stent placed.Three months ago,he suffered from coronary spasms,with three vessels involved,after surgery for cervical spine injury.He started having progressive dysphagia 4 wk prior and was diagnosed with MG via serologic tests,and computed tomography declared a thymoma in the anterior mediastinum.After the symptoms of MG subsided,he was referred for thy-mectomy.The operation was uneventful until the closing of the sternal wound.Electrocardiography showed sudden onset ST elevation,followed by ventricular tachycardia and severe hypotension.Cardiopulmonary cerebral resuscitation was initiated immediately with electrical defibrillation,extracorporeal membrane oxygenation was performed due to refractory cardiogenic shock,and the patient was transferred to an angiography room.Angiography showed diffuse CAS with three vessels involved.Intracoronary isosorbide dinitrate and adenosine were administered,and then the patient was transferred to the intensive care unit.CONCLUSION Our case highlights the importance of being prepared for clinical situations such as the one described here and suggests the necessity of developing an appropriate anesthesia plan that includes proactive analgesia and preemptive coronary vaso-dilators.

The Effect of Preoperative AchR-Ab Level to the Prognosis in Operated Myasthenia Gravis Patients

Objective: Seropositive myasthenia gravis (MG) depends on the presence of acetylcholine receptor antibodies (AchR-Ab) against nicotinic acetylcholine receptors at the postsynaptic neuromuscular junction. In this study, we investigated the effect of AchR-Ab levels to symptoms and treatment in the MG patients underwent surgery for thymic pathology. Materilas and Methods: The records including level of preoperative AchR-Ab, type of thymic pathology, the changes of symptoms and treatment after surgery for thymic pathology of 37 MG patients between January 2007 and December 2015 have been viewed retrospectively. Results: The mean age of 37 patients (21 females, 16 males) was 40.2 ± 14.9 years (range, 18 to 75 years). The mean of the level of AchR-Ab was 144.7 ± 427.6 nmol/L (range, 0.1 to 1806 nmol/L). In the patient group including the reduced use of anticholinesterase after surgery the mean of level of AchR-Ab was 241.3 nmol/L while it was 10.8 nmol/L in the patient group including the non-reduced use of anticholinesterase (p = 0.082) after a mean follow-up period of 23 months postoperatively. The mean levels were 246.7 nmol/L and 8.5 nmol/L for the reduced and non-reduced use of corticosteroid patient groups, respectively (p = 0.001). In the 25 patients with fewer symptom after surgery the mean of the AchR-Ab level was 205.3 nmol/L while it was 18.3 nmol/L in the patients without any changes (p = 0.071). Conclusion: We concluded that the preoperative level of AchR-Ab was associated with postoperative dosage of anticholinesterase and corticosteroids and severity of symptoms postoperatively. We think that the levels of AchR-Ab titers can be a marker for the efficacy of thymic surgery.

Myasthenia gravis in pediatric and elderly patients

Objective To determine whether the clinical and pathologic characteristics and prognoses of myasthenia gravis (MG) patients below 15 years differ from those patients over 50 years after thymectomy. Methods We reviewed the registry material of 30 pediatric and 32 elderly MG patients after thymectomy,including their age,sex,clinical classification,pathological types,and prognoses. The Chi-square test or Wilcoxon’s rank-sum test was used to determine the statistical differences between the children and elderly groups.Results No significant difference was seen in sex distribution between the two groups (Chi-square test, P =0.625),but there were differences in clinical classification: more type Ⅰ was observed in the pediatric group than in the elderly group,but more type Ⅱor Ⅲ was seen in the elderly group (Wilcoxon's rank-sum test,P <0.001). As to pathological types,the pediatric group was also significantly different from the elderly group (Chi-square test,P <0.01). All of the patients (100%) in the pediatric group had thymus hyperplasia,but in the elderly group more than half (56.26%) were found to have thymoma (benign or malignant). The prognoses after thymectomy were better in the pediatric group than in the elderly group (Wilcoxon's rank-sum test,P <0.001). Conclusions Because the prognoses are generally better than those of the elderly patients,we should be careful when operating on pediatric patients of ocular type. The elderly patients tend to receive more aggressive treatment because of more severe generalized types often associated with thymoma and poor prognoses. Both pediatric and elderly patients are seldom associated with other autoimmune disease.

Anesthetic management of a patient with stiff-person syndrome and thymoma: a case report

Stiff-person syndrome （SPS, also called stiff-man syndrome） is a rare neurological disease with autoimmune features. It is characterized by fluctuating and progressive muscle rigidity, and episodic spasm that prominently involve axial and limb musculature.1,2 Herein we report a case of anesthetic management of a patient with SPS for thymectomy and review several other cases.