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PubMed2005

Factors influencing the outcome of transsternal thymectomy for myasthenia gravis.

BACKGROUND: Thymectomy is one of the current treatment strategies for patients with myasthenia gravis (MG); however, the selection criteria for surgery remain controversial. METHODS: The demographic data and the surgical results of 168 patients with MG who underwent transsternal thymectomy from June 1986 to December 2000 were retrospectively reviewed. Follow-up information was obtained by review of the hospital records or telephone contact. The postoperative status of MG was assessed at the interval of 1, 3 and 6 months and then annually. The complete remission rate (CRR) between groups was compared. RESULTS: A total of 168 patients, including 69 male patients and 99 female patients, with a mean age of 38.3 years (range 13-80 years), were analyzed. The symptom duration before operations was from 1 to 312 months with a mean of 33.8 months. Complete follow-up information was obtained on 154 patients (91.6%) with a mean follow-up duration of 98.9 months. Complete remission was achieved in 89 of 154 patients (57.8%) and marked clinical improvement in 47 patients (30.5%). Total improvement rate was 88.3%. Seventeen of 24 patients (70.8%) with ocular MG and 18 of 35 patients (51.4%) with thymoma had reached complete remission during the follow-up period. The CRR increased with each consecutive year and reached the plateau in the fourth postoperative year. There was no surgical mortality. The complication rate was 16.6%. Univariate analysis demonstrated that age <35 years old (P = 0.0001), symptom duration before operation <24 months (P = 0.01) and absence of preoperative steroid treatment (P = 0.04) were favorable prognostic factors. Multivariate Cox regression analysis revealed age <35 years old (odds ratio = 3.645, P = 0.001), symptom duration before operation <24 months (2.311, P = 0.041) were favorable prognostic factors for patients having transsternal thymectomy. CONCLUSIONS: Transsternal thymectomy is feasible in the management of patients with MG at all stages with high improvement rate and low surgical morbidity. Those patients aged 35 years or less at operation, with symptoms developed <24 months before operation, may benefit more from thymectomy. MG patients with thymoma did as well as patients without thymoma, and 18 of 35 patients with thymoma had reached complete remission during the follow-up period. Thymectomy seems to be beneficial also for ocular MG.

Adolescent↗
PubMed1991

Actuarial analysis of the occurrence of remissions following thymectomy for myasthenia gravis in 400 patients.

The role of thymectomy in the treatment of myasthenia gravis (MG) was analysed in 400 patients affected with generalised MG operated on between 1974-83, and prospectively followed up for five years after surgery. The occurrence of stable remission (SR) (that is, complete clinical drug-free remission that remains stable for all the subsequent follow up) was the endpoint of survival analyses and the distribution of SR time (SRT, that is, the interval from thymectomy to the occurrence of SR) was assessed by actuarial and Cox multivariate analyses. SRT distribution after surgery showed a slow progressive increase of cumulative SR rate that could both be ascribed to a delayed effect of thymectomy as well as reflect the natural history of MG, itself characterised by an increasing probability of spontaneous remission with time. SRT distribution was similar after stratification for all variables studied except when patients without thymoma were stratified for the need for immunosuppressive treatment in addition to thymectomy. Patients without thymoma who did not require additional immunosuppressive therapy (n = 130) had the highest SR rate occurring in the two years after thymectomy, and differed from patients treated with immunosuppressive drugs who showed the highest SR rate five years after surgery. Actuarial analysis has therefore identified a subgroup of patients where SR, occurring in the first years after surgery, is more likely to be ascribed to thymectomy than merely reflect the natural course of the disease.

Actuarial Analysis↗
PubMed1993

Thymectomy and azathioprine have no effect on the phenotype of CD4 T lymphocyte subsets in myasthenia gravis.

The influence of thymectomy and long term immunosuppression on the phenotype of CD4 T lymphocyte subsets, which were defined by the restricted expression of CD45RA and CD45RO markers, was studied by double immunofluorescence in 29 patients in different clinical stages of generalised myasthenia gravis. In the acute stage of myasthenia, before thymectomy and immunosuppression, no differences in CD4 subsets were observed in the peripheral blood from nine patients and 21 matched controls. Four to seven weeks after thymectomy, there was a slightly decreased proportion of CD4+CD45RO+ (UCHL1+) memory cells (p < 0.05, paired t test). Patients on steroids showed a more pronounced decrease of CD4+CD45RO+ cells suggesting, in addition, a drug-related effect. CD4 subsets (CD45RA, CD45RO, and CD29 positive) in the peripheral blood compartment remained largely stable over 18 to 24 months thereafter. In addition, CD4 subsets were examined in 20 patients with myasthenia gravis who had had a thymectomy between two and 17 years before. With the exception of patients on steroids, there were no differences in CD4 subsets in patients on or off azathioprine. These data did not show any relation of CD4 T cell subsets to the clinical course of myasthenia, or significant changes due to thymectomy, or immunosuppression with azathioprine. These results also complement the authors' clinical experience that thymectomy in adults does not leave a deficit in cell-mediated immunity. The slight change associated with steroid treatment might deserve further attention.

Adolescent↗
PubMed2005

Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis.

STUDY OBJECTIVES: Minimal-access thymectomy has become increasingly popular as surgical treatment for patients with nonthymomatous myasthenia gravis (NTMG) because of its comparable efficacy, safety, and lesser degree of tissue trauma compared with conventional open surgery. We reviewed and analyzed our data on video-assisted thoracic surgery (VATS) thymectomy and present the clinical outcomes according to the Myasthenia Gravis Foundation of America classification. DESIGN: A retrospective review of VATS thymectomy for NTMG in a university hospital over a 12-year period. Data were collected from the medical records and supplemented with telephone surveys. The impact of surgery and other variables potentially affecting complete stable remission (CSR) were calculated using Kaplan-Meier survival curves; comparisons between survival curves was performed using the log-rank test. RESULTS: A total of 38 consecutive patients underwent VATS thymectomy for NTMG. Median postoperative stay was 3 days. Pathologic examination revealed thymic hyperplasia in 61.1% of cases, normal thymus in 22.2%, and thymic atrophy in 16.6%. There was no perioperative mortality; complications occurred in four patients. After a median follow-up of 69 months, 91.6% of patients experienced improvement, with crude CSR achieved in 22.2%. Kaplan-Meier survival curve demonstrated a 75% CSR rate at 10-year follow-up. On univariate analysis, only disease duration < or = 12 months (p = 0.03) was associated with a statistically significant improvement in CSR. CONCLUSIONS: VATS thymectomy for NTMG results in symptomatic improvement in the vast majority of patients, with a high rate of CSR. The procedure is associated with low morbidity and no perioperative mortality. Future studies on thymectomy for myasthenia gravis should be reported in a standardized manner to allow accurate comparisons between results in the absence of randomized prospective trials.

Adult↗
PubMed1975

Transcervical thymectomy in myasthenia gravis.

Since 1967, transcervical thymectomy has been the procedure of choice for all patients with nonthymomatous myasthenia gravis and a selected group of patients with thymomatous myasthenia gravis operated upon at the Mount Sinai Hospital. A total of 180 transcervical thymectomies have been performed. In 12 patients, a pre-existing tracheostomy was present. Morbidity was minimal, limited to three instances of bleeding, five of pneumothorax, one of self-limited chylothorax, and one wound infection. One postoperative death from an unrelated cause occurred in 1967. The postoperative course has been smoother and the management of the myasthenia gravis considerably easier than those following transthoracic approaches. Consequently, routine elective tracheostomy at the time of thymectomy has been abandoned. The average period of hospitalization does not exceed one week. As a result of the minimal risk involved, indications for thymectomy now include all patients with generalized myasthenia gravis, and the procedure is performed earlier in the course of disease. Postoperative electromyographic findings show immediate improvement in the majority of patients operated upon during the first year in which symptoms occur. Transcervical thymectomy arrests the progress of the disease, decreases the mortality rate, and has long term results equal to those of transthoracic approaches. Earlier remissions, fewer germinal centers, and a smaller number of thymomas were noted in patients operated upon early in the course of the disease. A decrease in neoplasms outside the thymus gland and in neonatal myasthenia gravis was also noted following thymectomy.

Breast Neoplasms↗
PubMed1977

Lymphocyte-mediated cytotoxicity: effects of ageing, adult thymectomy and thymic factor.

Adult thymectomy, as well as ageing, depressed splenic lymphocyte-mediated cytotoxicity (LMC) in the mouse. Ageing depressed significantly LMC as early as 19 weeks of age, independently of the number of cells used for immunization. Thymectomy affected LMC only when supoptimal numbers of immunizing allogeneic cells were used. This effect peaked at 6 to 12 weeks after thymectomy. No difference between thymectomized and normal mice was observed when LMC was tested 16 to 20 weeks after thymectomy, at an age when normal control mice themselves already showed a lowered LMC due to ageing. The effect of in vivo treatment with a circulating thymic factor (TF), which was shown to disappear with ageing as well as after adult thymectomy, has been tested in adult thymectomized mice and normal young and ageing mice. TF treatment prevented LMC depression in adult thymectomized mice, whereas it depressed paradoxically splenic LMC in normal young and old mice. The possible mechanisms of the effects of adult thymectomy, ageing, and thymic factor on the different T cell subsets involved in allogeneic killer cell generation are discussed.

Aging↗
PubMed2003

Thoracoscopic thymectomy in children with myasthenia gravis.

Although conservative medical management is the mainstay in the treatment of myasthenia gravis (MG), severest forms of the disease often require surgical thymectomy. Thoracoscopic thymectomy (TT) represents a minimally invasive alternative to traditional thymectomy via sternotomy. We present our preliminary experience with TT as definitive treatment for severe forms of MG. The charts of 5 children (4 girls and 1 boy; age range, 11-17 years) who underwent TT for MG were retrospectively reviewed. TT was typically performed via left thoracoscopy using 4- or 5-mm ports with 1 of the ports enlarged at the end of the procedure for specimen retrieval. Thymic veins were identified and ligated with surgical clips in all cases. Surgical parameters assessed were the following: operating time, intra- and postoperative complications, length of postoperative stay, and resolution of symptoms. Follow-up ranged from 6 months to 2 years. All 5 TTs were successfully completed. In 1 case, right-sided thoracoscopy was added to ensure complete gland excision. Surgical pathology in all cases demonstrated complete excision. Mean operating time was 121 minutes (range 88 minutes to 188 minutes). There were no intra- or postoperative complications. Length of postoperative stay averaged 1.6 days (range, 1 to 3 days). Four of 5 (80%) had clear resolution of symptoms with 1 showing minimal resolution at 6 months. Thoracoscopic thymectomy is a safe and potentially attractive alternative to traditional thymectomy via median sternotomy in severe forms of myasthenia gravis. Complete thymectomy, the goal of traditional surgical treatment for myasthenia gravis, can effectively by achieved via this minimally invasive technique.

Adolescent↗
PubMed2004

[Thymectomy and muscle antibodies in myasthenia gravis].

BACKGROUND: Thymectomy as a treatment for myasthenia gravis (MG) is widely carried out as there is good clinical evidence for post-thymectomy improvement in younger MG patients. MATERIAL AND METHODS: We examined the relationship between thymectomy, MG severity, the occurrence of muscle autoantibodies against acetylcholine receptor (AChR), titin, and ryanodine receptor (RyR), and pharmacological treatment in 52 early and 43 late-onset MG patients. RESULTS AND INTERPRETATION: Thymectomy in early-onset MG gave a rapid, highly significant, and long-lasting improvement during the first one to two years after surgery. Several patients had a remission. In late-onset MG, thymectomy did not provide the same improvement, but these patients responded well to immunosuppressive drug treatment, which was necessary in 75% of late-onset MG patients compared to only 25% of early-onset patients. The concentration of AChR, titin, and RyR antibodies did not predict the outcome of thymectomy. The occurrence of titin/RyR antibodies in late-onset MG indicated a less favorable prognosis.

Adolescent↗
PubMed1989

Cervical thymectomy in the treatment of myasthenia gravis.

Treatment modalities in myasthenia gravis consist of surgery, chemotherapy and plasmapheresis. Thymectomy can be accomplished either through a median sternotomy or through a small, transverse cervical incision. Forty patients who underwent cervical thymectomy for non-thymomatous myasthenia gravis were studied retrospectively. Twenty-six patients (65%) showed a favourable response to thymectomy and there were statistically significant improvements in myasthenic symptoms and reductions in medication requirements. Age, sex, duration of symptoms and thymic histology were not predictive of response to thymectomy. Operative mortality was zero and operative morbidity was minimal. During the last 6 years, only two of 22 patients required admission to the intensive care unit postoperatively. The postoperative hospital stay ranged from 2 to 23 days. Cervical thymectomy does not preclude later sternotomy in those patients who fail to respond favourably. We therefore recommend cervical thymectomy as the initial surgical procedure in the treatment of non-thymomatous myasthenia gravis.

Adolescent↗
PubMed1988

"Maximal" thymectomy for myasthenia gravis. Results.

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation has been complete removal of the thymus, but there has been controversy about the surgical technique and its relation to results. Surgical-anatomic studies have shown gross and microscopic thymus widely distributed in the neck and mediastinum. We believe that an en bloc transcervical-transsternal "maximal" thymectomy is required to remove all thymic tissue predictably. Ninety-five patients with generalized myasthenia gravis underwent "maximal" thymectomy consecutively between 1977 and 1985 and were evaluated 6 months to 89 months after operation. In Group A (N = 72), myasthenia gravis without thymoma, the uncorrected data revealed that 96% (69) had benefited from operation: 79% (57) had no symptoms; 46% (33) were in remission; 33% (24) were symptom free when receiving minimal doses of pyridostigmine; and none were worse. Life table analysis yielded a remission rate of 81% at 89 months. In group B (N = 8), myasthenia gravis without thymoma for which patients underwent reexploration for incapacitating weakness after earlier transcervical or transsternal operations, residual thymus was found in all. One patient was in remission, two were symptom free when receiving medication, one was unchanged, and none were worse. In group C (N 15), myasthenia gravis and thymoma, two patients were in remission and nine were symptom free when receiving medication. Two patients in this group died 2 and 4 years postoperatively in crisis. Response to thymectomy in group A was greater in patients with mild myasthenia gravis and may have been better in patients who had symptoms for less than 60 months preoperatively, but the response did not depend on age, sex, presence or absence of thymic hyperplasia or involution, or titers of acetylcholine receptor antibodies. The response to thymectomy in group B was striking but slower than in group A, perhaps because symptoms were more severe and of longer duration. The response in group C was also less good than in group A and proportionately fewer benefited. These results support the recommendation for thymectomy in the treatment of patients with generalized myasthenia gravis and indicate the desirability of a maximal procedure. For persistent or recurrent severe symptoms after previous transcervical or submaximal transsternal resections, reoperation by this technique is also recommended.

Actuarial Analysis↗
PubMed1988

The outcome of thymectomy in nonthymomatous myasthenia gravis.

From October 1979 to December 1984, 77 patients with nonthymomatous myasthenia gravis underwent thymectomy and 74 patients were available for careful follow-up study in this review. Among these 74 patients, 18 were male and 56, female. Their ages ranged from 13 to 68 years with an average age of 30.2 years. Men tend to be affected at a later age than women (an average age of 38.0 versus 26.1 years). Duration of the disease was from one to 30 years, with an average of 4.2 years. A sternal-splitting incision was performed for all patients. Thymectomy was made by removal of all anterior mediastinal fat between the pleuropericardial reflection and phrenic nerve bilaterally. Seventy of the 74 patients benefited from thymectomy. Of these, 34 patients had remission and 36 patients had substantial improvement; three patients did not improve after thymectomy but did not increase in severity of symptoms or medication requirement. There was no postoperative death. Myasthenic crisis developed in four patients and five patients had pulmonary complications. These nine patients were among the 21 patients who did not receive either plasmapheresis preoperatively or a high dose of steroids perioperatively. Early thymectomy is recommended for patients with nonthymomatous myasthenia gravis. We also recommend that patients undergoing thymectomy should be treated either with plasmapheresis preoperatively or with high doses of steroid perioperatively.

Adult↗
PubMed1984

The effect of thymectomy on lupus-prone mice.

The effect of neonatal thymectomy on the induction and/or modification of murine SLE disease was examined in several representative groups of mice with early-life SLE (MRL/Mp-lpr/lpr females, BXSB males, (NZB X W)F1 females, (NZW X BXSB)F1 males and females), late-life SLE (MRL/Mp-+/+ and BXSB females), and normal strains (BALB/c and C57BL/6 females). Our results indicated that thymectomy prevented disease only in the MRL/Mp-lpr/lpr SLE mice, and that this effect diminished as thymectomy was delayed beyond 3 wk post-natally. In the other SLE mice studied, neonatal thymectomy did not modify disease symptoms to any significant degree. Moreover, depletion of mature T cells from donor BXSB male bone marrow did not affect the expression of early-life SLE in thymectomized BXSB female recipients. Neonatal thymectomy did not induce SLE in normal mice. Of note, neonatal thymectomy did not completely deplete the Thy-1.2+ cell population, i.e., 10 to 15% remained in the spleens of the thymectomized mice. This incomplete T cell depletion, together with the previously demonstrated dependence on and hyperresponsiveness of BXSB and (NZB X W)F1 B cells to T helper cell-derived accessory signals, cast doubts on earlier conclusions that B cells from some SLE mice can autonomously proliferate and differentiate to autoantibody-secreting cells. It seems more appropriate to conclude that B cells from the various SLE mice vary in their degree of response to, and production of, T cell-derived helper signals, and thus in their expression of B cell hyperactivity and disease.

Aging↗
PubMed1978

Thymectomy in patients more than forty years of age with myasthenia gravis.

Until recently, thymectomy has been reserved for patients with myasthenia gravis in the younger age groups. The use of transcervical thymectomy, with its reduction in morbidity and mortality, has allowed us to study the effects of thymectomy in the older age group. The records of 525 patients who underwent thymectomy were reviewed and divided into two groups: those less than and those more than 40 years of age. The incidence of thymomas was greatest in the older than 40 year group. This age group without thymoma was also noted to have a high incidence of absent germinal centers. The postoperative remission rates as well as the electromyographic improvement rates were comparable for both age groups. The evidence presented indicates that thymectomy improves the clinical course of myasthenia gravis in all age groups studied. We recommend transcervical thymectomy for all patients with generalized myasthenia gravis, regardless of age.

Adult↗
PubMed1983

Thymectomy in multiple sclerosis. Two preliminary trials.

In two preliminary trials, thymectomy was performed on 35 multiple sclerosis (MS) patients, with (Group 1) or without (Group II) azathioprine therapy for 1 year. Formal studies of clinical neurologic status were conducted at yearly intervals after operation. Each group was compared with carefully matched control patients. Group I patients showed significant improvement in total functional groups (Kurtzke scale) and pyramidal functions 1 and 2 years following thymectomy. Other individual functions showed no significant difference. There was a statistical improvement in disability status (Kurtzke) for patients with relapsing-remitting MS 1 and 2 years following thymectomy. This subset also had a significant decrease in MS exacerbations. Group II patients showed none of the favorable trends seen in Group I. Functional groups, disability status scale, and exacerbations were similar to those of the control patients. Several studies indicate azathioprine therapy alone is of questionable benefit in MS. In myasthenia gravis (MG), the full immunosuppressive effect of thymectomy may not be realized for several years. Therefore, it is possible that in Group I patients a dual mechanism of immunosuppression--azathioprine and thymectomy--is yielding a favorable response not yet apparent in the Group II patients having thymectomy alone. If our data still appear favorable after a third follow-up year, a formal pilot study will be undertaken.

Adult↗
PubMed1975

Transcervical thymectomy in renal transplant recipients: surgical complications and possible effect on long-term allograft survival.

Between January 1963 and December 1967, 59 renal transplant recipients underwent thymectomy with or without splenectomy as an adjuvant to standard immunosuppression. All thymectomies were performed transcervically. By internal comparison long-term renal allograft survival was better in recipients who had thymectomy, when compared to those who did not. There were no significant surgical complications associated with transcervical thymectomy and the completeness of thymectomy was judged satisfactory. The role of thymectomy as an adjuvant operation in human renal transplant recipients should be re-examined.

Cadaver↗
PubMed1993

Prevention by thymectomy of tolerance induced by intrathymic injection of donor splenocytes.

BACKGROUND: We have recently demonstrated indefinite donor-specific cardiac allograft survival after the intrathymic injection of donor splenocytes and simultaneous injection of antilymphocyte serum (ALS) in a fully major histocompatibility complex-mismatched rat combination. In this study we performed thymectomy to determine the length of time required for donor alloantigen to be present in the recipient thymus to induce tolerance. METHODS: Male Buffalo (BUF; RT1b) rats at 4 to 8 weeks of age underwent intrathymic injection of 25 x 10(6) Lewis (LEW; RT1(1)) splenocytes and simultaneously received an intraperitoneal injection of 1 ml ALS. To determine the kinetics of tolerance induction, the BUF recipients underwent thymectomy on days 1, 3, or 7 after the initial intrathymic injection of alloantigen and intraperitoneal ALS. Twenty-one days after intrathymic alloantigen injection and ALS, all rats underwent transplantation with a heterotopic LEW cardiac allograft. RESULTS: Thymectomy performed 1 (mean survival time, 6.8 days) and 3 (mean survival time, 8.0 days) days after donor alloantigen injection and ALS did not affect the normal rejection of LEW cardiac allografts. In contrast, thymectomy 7 days after intrathymic alloantigen injection and ALS resulted in indefinite survival of cardiac allografts in 75% of recipients (mean survival time > 77.0 days). In addition, allospecific cytotoxic T lymphocyte activity and interleukin-2 production were markedly decreased in those recipients undergoing thymectomy after 7 days compared with untreated control rats and recipients undergoing thymectomy 1 and 3 days after alloantigen injection. CONCLUSIONS: The presence of the thymus for at least 7 days after intrathymic alloantigen injection and intraperitoneal ALS allows the development of indefinite donor-specific cardiac allograft tolerance.

Animals↗
PubMed1989

[Clinical examinations of thymic abnormalities and significance of thymectomy in the patients with autoimmune disease].

Results and significance of thymectomy in 427 patients with autoimmune disease, which include myasthenia gravis, ulcerative colitis. Behçet's syndrome and others, were studied. Preoperative pneumomediastinography was useful to delineate the outline of the nontumorous thymus and small "latent thymoma". The thymus was almost always successfully removed by our procedure "thymectomy via the suprasternal notch" (Method I), but the procedure combined with dissection through a parasternal incision (Method II) was frequently performed. Method II has been routinely adopted since 1976. Thymectomy was performed on a series of 180 patients with myasthenia gravis associated with nontumorous thymic abnormalities. In the resected thymuses, lymphoid follicle formations, which are often encountered in other autoimmune diseases, were found in 74% of cases. Follow-up observation, ranging 2 to 17 years after surgery, revealed complete recovery and significant improvement in 100 (75%) out of 133 patients with nontumorous thymic abnormalities. Thymectomy was also performed in 44 myasthenia gravis patients with thymoma, including 13 small "latent thymoma". Seventy-seven thymectomized patients with ulcerative colitis were also studied, and in these resected thymuses lymphoid follicle formations were fond in 45%. Follow-up observation revealed 84% inactive condition (counted by patient year) after thymectomy compared with 50% before operation. In the patients with Behçet's syndrome, recurrence and progression of skin, oral and genital lesions were markedly suppressed after thymectomy.

Adolescent↗
PubMed1984

Thymectomy and chronic relapsing experimental allergic encephalomyelitis in guinea pigs.

Chronic relapsing experimental allergic encephalomyelitis (EAE) was induced in young Dunkin Hartley guinea pigs by a single sensitization with guinea pig spinal cord homogenate. The effect of either newborn thymectomy or young adult thymectomy on the clinical course of chronic and relapsing EAE was studied and evaluated statistically by Student's t test. All the animals that underwent thymectomy showed a significant delay in the onset of the disease compared with control groups. In addition, in the young adult guinea pigs in which thymectomy was done, the incidence of clinical disease was decreased. No substantial differences, however, were observed in the severity of the disease and number of remissions or relapses between guinea pigs in which thymectomy was done and in which clinical symptoms developed and controls.

Animals↗