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PubMed2002

Paradigm shift in surgical approaches to thymectomy.

BACKGROUND: Thymectomy is an established therapy in the management of myasthenia gravis (MG) used in conjunction with medical treatment. The optimal surgical approach to thymectomy, however, has remained controversial. METHOD: The present review discusses the author's experiences of and the literature regarding the management of MG using the video-assisted thoracic surgery (VATS) approach. RESULTS: This approach was shown to be technically safe in experienced hands and associated with less postoperative pain, better preservation of lung function in the early postoperative period and better cosmetic results than alternative techniques. The intermediate term results of VATS are comparable to those of more radical approaches. It is hoped that this patient-friendly approach will lead to greater support by patients and their neurologists, for earlier surgery. CONCLUSION: VATS is an attractive, alternative approach to thymectomy.

Adolescent↗
PubMed2002

Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis.

Thymectomy is still widely carried out in myasthenia gravis (MG) patients, but its role, especially in late-onset MG patients, is not established. These patients are immunologically heterogeneous, some with thymoma-like and others with early onset-like features. We evaluated whether any therapeutic effects of thymectomy correlate with the presence of non-acetylcholine receptor (AChR) muscle antibodies. The severity of MG, and titin and ryanodine receptor (RyR) antibodies, were assessed yearly starting from MG onset in 21 thymectomized and 22 non-thymectomized AChR antibody positive late-onset MG patients, who were followed for 2, 3 and 5 years. Clinical or pharmacological remission were seen in six of 11 titin antibody negative but none of the 10 titin antibody positive thymectomized patients, however, the non-thymectomized cases showed an opposite trend. The three MG-related deaths were all in patients with titin antibodies. There was no significant difference in MG severity between thymectomized and non-thymectomized patients; 2 years after MG onset, both groups were significantly improved. This study showed no dramatic benefit from thymectomy in late-onset MG in general. Any limited improvement appeared less likely in cases with titin and/or RyR antibodies.

Age of Onset↗
PubMed2006

Microscopic polyangiitis associated with thymoma, exacerbating after thymectomy.

A variety of autoimmune diseases has been associated with thymoma, and thymectomy does not always induce remission of these disorders. This case report describes a 50-year-old man who presented with migratory polyarthritis and an anterior mediastinal mass that proved to be a thymoma. Five months after thymectomy, the patient presented with worsening polyarthritis, hematuria, and azotemia. Based on elevated titers of antineutrophil cytoplasmic antibodies directed against myeloperoxidase and renal biopsy showing crescentic necrotizing glomerulonephritis, microscopic polyangiitis was diagnosed. After remission-induction therapy with prednisone and cyclophosphamide, articular symptoms and renal manifestations resolved. Microscopic polyangiitis was not associated previously with thymoma, and this case broadens the spectrum of autoimmune disorders seen with this tumor. Progressive disease seen after thymectomy in this patient has potential implications regarding the pathophysiological characteristics of microscopic polyangiitis and management of patients with this clinical association.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Morbidity after transsternal thymectomy for myasthenia gravis: a changing perspective?

A detailed assessment of recent changes in morbidity and mortality after transsternal thymectomy for myasthenia gravis is pending. To this end, a retrospective analysis was carried out of morbidity and mortality rates in 125 patients subjected to transsternal thymectomy for myasthenia gravis in the periods 1976-85 (1st decade) and 1986-95 (2nd decade). Composition of patients did not change much over time, except for more concomitant preoperative disease in the second decade (p = 0.001). None the less, complication rates were not higher, nor did the pattern of complications alter. Mortality was nil in both decades. There was no difference over the decades as to length of ventilation, intensive care treatment, or overall hospitalization. Most complications did not reveal a monocausal relationship, suggesting that a combination of risk factors was implicated. Further reductions in future morbidity rates after transsternal thymectomy for myasthenia gravis seem unlikely as patient preoperative state is unlikely to improve. In the light of the deteriorating preoperative patient condition, constant postoperative morbidity rates indicate that patient care has in fact improved.

Adult↗
PubMed1983

Myasthenia gravis. Immunological studies in a young child treated with thymectomy and immunosuppressive drugs.

A case of severe myasthenia gravis diagnosed in a 12-month-old girl is described. Thymectomy at 15 months of age had only a negligible effect on the course of the disease. Treatment with cholinesterase inhibitors, prednisolone and azathioprine was started. After one year of combined treatment she was symptomfree and 3 years later treatment with cholinesterase inhibitors and prednisolone was discontinued. Attempts to withdraw azathioprine have so far been unsuccessful, leading to relapse of the disease. IgG-antibodies against cholinergic receptors were lowered to near normal, whereas the levels of total plasma immunoglobulins remained normal. The proportion of T-lymphocytes in peripheral blood was reduced during the first weeks after thymectomy, but has since been normal. Lymphocyte function measured by PHA stimulation remained normal all the time. The girl grew and developed normally without complicating infectious diseases in spite of her severe disease, thymectomy and immunosuppressive treatment.

Autoantibodies↗
PubMed1982

Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirement of Lyt-1 cells in normal female mice for the prevention of oophoritis.

Autoimmune oophoritis that develops in A/J mice after neonatally thymectomy (NTx) was prevented by a single intraperitoneal injection of spleen cells or thymocytes from normal adult female mice. Prevention of oophoritis was achieved when spleen cells were given within 2 wk after Tx. When spleen cells were obtained from neonatally oophorectomized mice, four times more cells were required for the prevention of oophoritis, but those from the mice oophorectomized on day 7 after birth had equivalent capacity to prevent oophoritis to those from normal female mice. The spleen cells from normal A/J mice that prevented the development of oophoritis in NTx A/J mice were Thy-1+, Lyt-1+,23-, Ia-, Qa-1-, sensitive to in vitro irradiation with 400 rad, resistant to administration of cyclophosphamide or anti-thymocyte serum, and were not eliminated by adult thymectomy. Thymocytes with oophoritis-preventing capacity were also found to be Lyt-1+,23- and TL-1,2,3-. These results seem to correlate well with the finding that the Lyt-1 subpopulation is substantially decreased in NTx mice. The results suggest that, in this post-thymectomy autoimmune oophoritis, NTx abrogates the Lyt-1 T cell subpopulation that serves as suppressive or regulatory cells over developing self-reactive cells directed toward ovarian antigens, and eventually may cause autoimmune oophoritis.

Aging↗
PubMed1998

Three day neonatal thymectomy selectively depletes NK1.1+ T cells.

Neonatal thymectomy of mice 3 days after birth but not at birth leads to T cell-mediated, organ-specific, autoimmune disease in a strain-dependent manner. The mechanisms that lead to disease in this model remain unknown, but the answer may lie in a deficiency of thymus-dependent cells or factors. One candidate is the relatively rare population of NK1.1 + T cells (NKT cells). Conventional alphabetaTCR+ T cells appear in the thymus from days 17-18 of embryogenesis and start emigrating to the periphery around birth, whereas the development of NKT cells is thought to be delayed until at least 1 week after birth. We have confirmed this to be the case in both (BALB/c x C57BL/6)F1 (autoimmune susceptible) and C57BL/6 (autoimmune resistant) mice. Moreover, examination of T cells (in spleen, lymph nodes, liver and bone marrow) from mice following 3 day neonatal thymectomy revealed a significant reduction in the presence of NKT cells in all tissues. However, the extent of depletion was generally more pronounced in (BALB/c x C57BL/6)F1 than in C57BL/6 mice, and the few remaining NKT cells in C57BL/6 mice were enriched for a CD4-CD8int subset which is absent from the thymus and may represent a distinct lineage of thymus-independent NKT cells. Given mounting evidence of a role for NKT cells in protection from autoimmune disease, it is possible that their specific removal by neonatal thymectomy may contribute to the susceptibility of these mice to autoimmune disease.

Animals↗
PubMed1991

Extubation after transsternal thymectomy for myasthenia gravis: a prospective analysis.

Recommendations concerning postoperative extubation after thymectomy for myasthenia gravis are presently based upon retrospective chart reviews. We present the results of a prospective investigation of time to extubation after thymectomy for 14 patients over a 12-month period based upon a protocol that included preoperative immunologic therapy, combined epidural and general anesthesia, postoperative epidural narcotic analgesia, and a standardized approach to discontinuation of ventilatory support. After a neurologist took measures to optimize preoperative neuromuscular function, all 14 patients received agents to produce lumbar epidural anesthesia and light general anesthesia. Muscle relaxants were avoided in all but one patient. Postoperative analgesia was initially maintained with epidural hydromorphone, then therapy was switched to patient-controlled intravenous morphine sulfate. Criteria for weaning from mechanical ventilation, first measured at the end of anesthesia, were partial pressure of oxygen (arterial) greater than or equal to 90 mm Hg (fraction of inspired oxygen = 0.40), partial pressure of carbon dioxide (arterial) less than or equal to 50 mm Hg, pH greater than or equal to 7.30, and respiratory rate less than or equal to 30 breaths/min. If these criteria were not met, ventilatory support was continued postoperatively with intermittent mandatory ventilation, and the patient was weaned gradually from this support. Criteria for extubation included meeting the criteria for weaning, vital capacity greater than or equal to 10 mL/kg, and inspiratory pressure better than -30 cm H2O. Criteria for reintubation included tachypnea (respiratory rate greater than 40 breaths/min), respiratory acidosis not due to narcotics, or vital capacity less than or equal to 8 mL/kg. The mean time to extubation was 9 hours (range, 0.75 to 25 hours). Mean preoperative vital capacity was 2.59 +/- 0.64 L (range, 1.90 to 4.20), which decreased approximately 50% to 1.19 +/- 0.39 L (range, 0.70 to 2.0) at the time of extubation. No patient required reintubation. Half of the patients required postoperative anticholinesterase therapy based upon serial neurologic examinations; there were no instances of cholinergic crisis. Thirteen patients returned to the ward on the first postoperative day, and one on the second day. Thirteen patients preferred epidural analgesia to patient-controlled analgesia. The time to extubation and average length of stay in an intensive care setting were markedly reduced compared to those reported in previous retrospective studies. We conclude that a multidisciplinary approach that optimizes neuromuscular function and decreases poststernotomy pulmonary insult will shorten the time to extubation and decrease the length of stay in the intensive care or recovery room after thymectomy.

Adolescent↗
PubMed1975

Thymectomy as immunosuppression in uremic patients.

Five uremic patients awaiting renal transplantation underwent transcervical thymectomy in an evaluation of the immunosuppressive effect of removal of the thymus in such transplantations. A number of immunological parameters, including lymphocyte transformation tests, were followed in these patients for up to 30 weeks after thymectomy. The number of B lymphocytes in the blood, stem cells in bone marrow, and T lymphocytes in lymph nodes decreased, whereas IgG, IgA, and IgM in four cases and C3 complement in all five cases increased. Blood leucocyte and lymphocyte counts did not show any characteristic changes. The T cell response of circulating lymphocytes was determined after stimulation with mitogens, specific antigens, and allogeneic cells in mixed lymphocyte culture, and showed a large increase. Thymectomy of uremic patients results in a considerable increase in immunocompetence in the first 30 weeks, indicating that it is not suitable as an immunosuppressive treatment.

Adult↗
PubMed1977

Allograft rejection in larval and adult Xenopus following early thymectomy.

The effect of thymectomy (performed on 7- to 8-day old larvae) on the development of alloimmunity in the clawed toad is examined. Rejection of first-set skin grafts applied in larval life (30 days of age) and at intervals following metamorphosis (70 to 370 days of age) was always impaired following thymectomy. However, most of the thymectomized animals, even those grafted as larvae and blocked in the larval state by thiourea treatment, were able to destroy the transplants, albeit with prolonged rejection times. The pattern of graft rejection in thymectomized larvae was similar to that seen in adults. After thymectomy, these seemed to be no improvement or impairment of the alloimmune response with the passage of time. Experiments with second-set grafts applied subsequent to first-set destruction demonstrated the existence of an alloimmune memory component throughout ontogeny in both control and thymectomized animals. The results indicate that a population of cells involved in graft rejection develops early in ontogeny, independent of the thymus and the emergency of bone marrow at metamorphosis.

Aging↗
PubMed2004

Thymectomy impairs but does not uniformly abrogate long-term acceptance of semi-identical liver allograft in inbred miniature Swine temporarily treated with FK506.

BACKGROUND: Long-term acceptance of semi-identical orthotopic liver transplants (OLTs) in inbred swine is induced by a 12-day course of FK506. To study whether acceptance is attributable to central or peripheral immune mechanisms, the effect of complete thymectomy was determined. METHODS: Total thymectomy was performed in 15 swine 3 to 4 weeks before OLT. Twelve of these animals received a 12-day course of FK506 after OLT, and three animals did not receive immunosuppression. Five additional nonthymectomized pigs received OLT and a FK506 regimen. Graft survival, liver function, histology, and cellular and humoral responses were assessed. RESULTS: Nonthymectomized, FK506-treated animals uniformly showed long-term acceptance of OLT and developed stable donor unresponsiveness. Of the 12 thymectomized, FK506-treated pigs, seven died of non-immunologic causes within 3 postoperative months, and five maintained their OLT for more than 6 months (range 180-450 days). Among these survivors, two developed a complete anti-donor response (mixed lymphocyte reaction [MLR], cell-mediated lymphocytotoxicity [CML], and immunoglobulin [IgG] antibodies) and eventually rejected their OLT at postoperative day 180. The three remaining pigs kept their liver allografts up to 450 days and developed a donor-specific unresponsiveness (a transient anti-donor MLR was observed during the follow-up but never an anti-donor CML or IgG antibodies). All three thymectomized, untreated animals rejected their allografts acutely and displayed a complete anti-donor response (MLR, CML, and IgG antibodies). CONCLUSIONS: Complete thymectomy before OLT impaired but did not uniformly abrogate long-term acceptance of semi-identical OLT, suggesting that peripheral immune mechanisms may be sufficient to induce long-term acceptance of liver allografts in some recipients.

Animals↗
PubMed1978

Modulation of age-related development of contact sensitivity in mice by adult thymectomy.

The effect of adult thymectomy on antibody production and on the development of contact sensitivity to picryl chloride in mice of different ages was studied. An age-dependent decline in the ability to develop contact sensitivity was found to be counteracted by thymectomy. In contrast, antibody production was regularly decreased by thymectomy in mice of all ages. A hypothesis is put forward in which the development of contact sensitivity may be regulated by long-lived thymus-dependent suppressor cells which do not affect antibody formation.

Age Factors↗
PubMed1997

Alopecia areata associated with myasthenia gravis and thymoma: a case of alopecia with marked improvement following thymectomy and high level prednisolone administration.

A 57-year-old Japanese woman who suffered from alopecia areata associated with myasthenia gravis (MG) and thymoma responded well to thymectomy and high doses of glucocorticosteroid administration. Several treatments for alopecia areata including administration of systemic prednisolone were attempted, but loss of hair on the scalp progressed. After thymectomy and high level glucocorticosteroid administration for MG, the lesions on the scalp improved within four weeks. Consequently, we suggest that this thymectomy and high level glucocorticosteroid administration assisted in improving the immune dysfunction causing the alopecic lesions in this patient.

Alopecia Areata↗
PubMed1992

Antibodies to acetylcholine receptors in myasthenia gravis. In vitro synthesis by peripheral blood lymphocytes before and after thymectomy.

Pokeweed mitogen (PWM)-driven in vitro synthesis of antibodies to the acetylcholine receptor (PSA) was studied in non-thymoma patients with myasthenia gravis. In a group of 46 patients, the occurrence of PSA was related to the presence of the thymus or, in operated patients, the absence of a clinical effect of thymectomy. Sixteen patients were followed before and soon after thymectomy. PSA disappeared in all patients, at least temporarily, between 6 weeks and 1 year afterwards, independent of the clinical course and eventual clinical effect of the operation. A recurrence was found only in one of the five patients who derived no benefit from the operation. These findings support the hypothesis that the therapeutic effect of thymectomy can be explained by removal of a source of autoreactive lymphocytes. There was no correlation between the changes in serum levels of a-AChR and clinical improvement, suggesting a minor role of circulating peripheral blood lymphocytes (PBL) and the thymus in the total production of a-AChR.

Adult↗
PubMed1981

Development of natural killer cell activity and genetic resistance to bone marrow transplantation with age: effect of neonatal thymectomy.

The effect of neonatal thymectomy on the development of splenic and bone marrow natural cell-mediated cytotoxicity and on genetic resistance to bone marrow transplantation was examined in mice. Natural cytotoxicity was measured by a 51Cr release assay; the ability to engraft foreign bone marrow was assayed by the spleen colony method. The natural cytolytic response of spleen cells increased progressively from youth to early adulthood, whereas that of the bone marrow declined during the same age period. Neonatal thymectomy significantly elevated the natural killer cell response of young mice only (4 weeks, spleen; 6 weeks, bone marrow). In other experiments, neonatally thymectomized and sham-operated mice were lethally irradiated at 4 or 6 weeks of age and injected with 2.5, 5.0 or 10 million rat marrow cells. Six days later spleen colonies were markedly reduced in both 4- and 6-week-old neonatally thymectomized mice with all rat marrow cell doses tested. Neonatal thymectomy did not alter the percentage of erythroid verus other colonies at either 4 or 6 weeks. In both thymectomized and sham-operated mice the number of colonies increased with increases in marrow cell dose. The data are suggestive of a production and dissemination to the spleen of cels involved in the natural cytotoxic response from the bone marrow.

Aging↗
PubMed1995

Long-term change of anti-acetylcholine receptor antibody in patients with myasthenia gravis after thymectomy.

Anti-acetylcholine receptor antibody (AChR Ab) plays an important role in the pathogenesis of myasthenia gravis (MG). We investigated the change of anti-AChR Ab titer after thymectomy of 10 MG patients including five patients whose age at onset was younger than 16 years. Anti-AChR Ab titer was increased in four of six patients with remission and three of four patients without remission. Change of anti-AChR Ab titer in individual patients showed an increase occurred 1-4 years after thymectomy. It is likely that thymectomy influences immune response and induces autoreactive lymphocytes and autoantibodies.

Adolescent↗
PubMed1991

Effect of thymectomy and immunosuppressive therapy on anti-neuroblastoma antibody levels in patients with myasthenia gravis.

Antibodies reacting with human neuroblastoma cells (NBL) are distinct from the "classical" anti-acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG). The influence of therapeutic interventions on serum anti-NBL antibody levels was followed in 42 MG patients. Thymectomy alone was performed in 28 patients while immunosuppressive medication was given to 14 patients out of whom 10 also had a thymectomy. In most patients serum anti-NBL antibody titers declined after thymectomy and/or during immunosuppressive treatment, though individual variations in the antibody response could be observed. Sequential examinations of individual patients revealed an association between the clinical severity of MG and anti-NBL antibody levels. No correlation between the treatment-induced changes of anti-NBL and anti-acetylcholine receptor (AChR) antibody titers could be observed during the follow-up period in MG patients positive for both types of antibodies. These findings further emphasize the immunological complexity of MG. Anti-NBL antibodies represent a pathogenic marker of the disease and display a regulation different from that of the anti-AChR antibodies.

Adolescent↗
PubMed1997

Post-thymectomy murine experimental autoimmune oophoritis is associated with reduced natural killer cell activity.

PROBLEM: Natural killer (NK) cells can influence the immune response by secreting potent lymphokines. It has been suggested that NK cells have a suppressive action on B cells, and that impaired NK cell activity may play a role in some types of autoimmunity. NK cell abnormalities have been reported in women with premature ovarian failure. We therefore examined NK cell activity during the development of murine experimental autoimmune oophoritis, which serves as a model for autoimmune ovarian failure in women. METHOD OF STUDY: Neonatally thymectomized and sham-operated C57B1/6 x A/J (B6A) mice were prepared and sacrificed at 4, 6, 8, and 10 weeks after surgery. Splenic NK cell activity was determined in groups of five or more mice by measuring the percent specific lysis of target YAC-1 lymphoma cells using a standard 4-hr chromium release cytotoxicity assay. The number of splenic NK cells in neonatally thymectomized and sham-operated animals was also compared using flow cytometry. In a subsequent experiment, interleukin 12 (IL-12; NK cell-stimulating factor) was administered to neonatal mice before neonatal thymectomy. RESULTS: Neonatally thymectomized mice with associated autoimmune oophoritis had a 75% reduction in the number of splenic NK cells, and 50% or greater reduction in splenic NK cell activity at 4, 6, and 8 weeks after surgery. IL-12 treatment before neonatal thymectomy maintained NK cell activity and was shown to ameliorate the associated autoimmune oophoritis. CONCLUSION: Murine post-thymectomy autoimmune oophoritis is associated with reduced NK cell number and impaired NK cell activity, and in these respects the model is similar to premature ovarian failure in women. Research to define the relationship between NK cell abnormalities and the mechanism of ovarian failure in this model might lend insight into the pathogenesis of premature ovarian failure in women.

Animals↗