Robotic thymectomy for myasthenia gravis surgical techniques and outcomes

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies are produced against post-synaptic acetylcholine receptors, thereby causing impairment of neuromuscular transmission. Diagnosis of MG is confirmed with the AChR antibody test and via an Electromyography. Although medical treatment with acetylcholinesterase inhibitors remains the main treatment of MG, in recent years thymectomy has become an integral part of the treatment algorithm. Numerous factors such as the Patient’s age, presence of AChR antibodies, or MuSK antibody, the severity of disease affect the decision of preforming the thymectomy. Historically thymectomy was preformed via sternotomy associated with significant morbidity. Advancement in the minimally invasive approaches to thymic resection has led to more acceptance of thymectomy in the management of MG. Among these approaches, robotic thymectomy is gaining popularity across the globe due to the unique advantages of the robotic platform like 3D visibility, enhanced dexterity, and wrist like articulating movements of instruments. This has led to less post-operative pain and morbidity; faster recovery and shorter hospital stay. Successful treatment of MG requires a multi-modality approach, which has led to the formation of MG teams in most academic centers, comprising of a specialist neurologist, intensivist, and thoracic surgeon. In this article, we describe the techniques and outcomes of the robotic thymectomy for MG.     

Autoimmune thrombocytopenic purpura, autoimmune hemolytic anemia and gastric cancer appeared in a patient with myasthenia gravis

We report a case of myasthenia gravis (MG) associated with autoimmune thrombocytopenic purpura (AITP) and autoimmune hemolytic anemia (AIHA), and after that gastric cancer appeared. A 51-year-old man began to suffer from fluctuated muscle weakness in 1985. Muscle weaknesses became exacerbated, and he was admitted to our hospital in 1989. He was diagnosed as MG associated with AITP. After a thymectomy (hyperplasia), prednisolone therapy was started, subsequently his condition was satisfactory. In March 1995, he developed severe anemia and icterus. He was diagnosed as Evans' syndrome (AIHA and AITP) with MG. High-doses of immunoglobulin administration improved the anemia, but thrombocytopenia continued. In November 2002, he suffered marked petechia; the platelet count decreased to 1000/microl. Methylprednisolone pulse therapy and platelet transfusion were started. Gastrofiberscopy was performed and biopsy specimens revealed signet cell-type adenocarcinoma. On December 19, 2002, subtotal gastrectomy and splenectomy were performed. After that, his condition has remained satisfactory, without MG symptoms or thrombocytopenia. This is the first such case report in the literature.     

Protein-losing enteropathy and premature ovarian failure in a young woman with systemic lupus erythematosus

Protein-losing enteropathy (PLE) and autoimmune oophoritis are unusual manifestations of systemic lupus erythematosus (SLE). Autoimmune oophoritis may result in menstrual disturbance and spontaneous premature ovarian failure. However, there is no validated examination to confirm the diagnosis and it is easily neglected in patients with ovarian insufficiency. A 31-year-old woman with SLE presented with PLE and autoimmune oophoritis during the long course of flares and remissions in her lupus activity. The synchronism implied the association between the two. Moreover, both conditions simultaneously had a good response to cyclosporine A (CsA) therapy.     

Autoimmune oophoritis with multiple molecular targets mitigated by transgenic expression of mater

Primary ovarian insufficiency (POI) resulting from ovarian autoimmunity is a poorly understood clinical condition lacking in effective treatments. Understanding the targets of the autoimmune response and induction of ovarian-specific tolerance would allow development of focused therapies to preserve fertility in an at-risk population. MATER (maternal antigen that embryos require) is a known ovarian autoantigen targeted in autoimmune syndromes of POI. We attempt to induce ovarian-specific tolerance via transgenic expression of the MATER antigen on potentially tolerogenic antigen-presenting cells (APC), which typically present antigen via the major histocompatibility complex (MHC) class II molecule. We hypothesize that expression of MATER in a MHC class II-dependent manner on APC can mediate induction of ovarian tolerance. We utilized a well-characterized murine model of ovarian autoimmunity, whereby oophoritis develops after d 3 neonatal thymectomy (NTx). Wild-type and transgenic mice, carrying an MHC Class II-driven Mater gene (IE-Mater), were subjected to NTx and assessed for evidence of autoimmune oophoritis. After disease induction by NTx, female mice carrying the IE-Mater transgene had significant reductions in histological oophoritis (56%) and circulating ovarian autoantibodies (28%) compared with wild-type females (94% and 82%, respectively). Incidence of other autoimmunity was unaffected as assessed by antinuclear autoantibodies. Transgenic expression of MATER in APC can induce antigen-specific tolerance with a significant reduction in ovarian autoimmunity. Lack of complete disease protection suggests that other antigens may also play a role in autoimmune oophoritis. As a known autoantigen in the human APS1 (autoimmune polyglandular syndrome type 1), which is associated with POI, MATER may represent a relevant target for future diagnostic and therapeutic clinical interventions.     

Sevoflurane for trans-sternal thymectomy in myasthenia gravis

Myasthenic gravis (MG) is an autoimmune disease associated with acetylcholine receptor deficiency. Patients with MG exhibit increased sensitivity to non-depolarising muscle relaxants. In an attempt to avoid neuromuscular blockers, we used sevoflurane in two myasthenic patients undergoing trans-sternal thymectomy. Inhalation of 8% sevoflurane in oxygen using vital capacity technique produced rapid, pleasant and smooth induction and provided good tracheal intubating conditions. In both patients anaesthesia was maintained with 1.5-2% end-tidal concentration of sevoflurane and nitrous oxide in oxygen without adjunctive neuromuscular blocking agents. There were minimal changes in cardiovascular variables and recovery was faster. It is suggested that sevoflurane may be the main anaesthetic for both induction and maintenance in myasthenic patients undergoing trans-sternal thymectomy.     

A Case of Inflammatory Bowel Disease Accompanied by Myasthenia Gravis

Abstract: A 62-year-old female visited our unit complaining of persisting diarrhea. She underwent a thymectomy for myasthenia gravis (MG) and a thyroidectomy for malignancy at age 58, and she was treated medically for MG fbllowing surgery. She also received a partial ileo-colectomy because of an intramural suppurative abscess of the terminal ileum at age 60. In her laboratory data, the anti-acetylcholine receptor antibody and antinuclear antibody were positive, and IgG as well as IgA were a high titer. X-ray and endoscopic examinations revealed the presence of stiff and narrow lesions accompanied by longitudinal ulcers of the descending colon, and rough and granular mucosa of the rest of the colon and stomach. An elemental diet was not effective, but her condition was relieved by the oral administration of prednisolone. This case was considered a case of inflammatory bowel disease ac-companied by MG and systemic immunological disorders.     

Relapse of autoimmune hemolytic anemia in Evans syndrome after thymectomy for pure red cell aplasia

A 81-year-old woman was referred to our hospital with pure red cell aplasia (PRCA) associated with a thymoma in May 2005. She had previously suffered from Evans syndrome which had been improved by prednisolone in 1999. She underwent a thymectomy, however her anemia subsequently got worse. Reticulocytopenia was noted and a marrow erythroid series was aplastic. Furthermore, both direct and indirect Coombs tests were positive, and the serum haptoglobin level was low. Based on these findings, the patient was diagnosed as having PRCA complicated with relapsed autoimmune hemolytic anemia (AIHA). The PRCA and AIHA were successfully treated with prednisolone and cyclosporine. To our knowledge, only one case of the PRCA complicated with AIHA after thymectomy has been reported. FoxP3 positive regulatory T-cells (Treg), which maintain immunological self-tolerance, were readily detectable in the excised thymoma. Thus, thymectomy resulted in removal of the Treg pool and might explain the autoimmune activation, believed to be one of the mechanisms of the post-thymectomy recurrence of the AIHA in this case.     

免疫治疗对重症肌无力病人淋巴细胞亚型的影响

目的 研究重症肌无力（ＭＧ）患者细胞免疫的异常改变和糖皮质激素及胸腺切除对各淋巴细胞亚群的影响。方法 采用免疫荧光双标记技术和流式细胞仪对３９例ＭＧ患者和１８例健康对照者周围血中淋巴细胞表型分析,并对１５例ＭＧ患者经患者经糖皮质激素治疗前后和７例ＭＧ患者在胸腺切除前后淋巴细胞亚群的百分率的变化进行观察。结果（１）ＭＧ患者总Ｔ细胞,总Ｂ细胞（ＣＤ１９＾＋）,传统Ｂ细胞（ＣＤ５＾－ＣＤ１９＾＋）,ＣＤ     

Therapeutic Apheresis in Myasthenia Gravis

Abstract: Plasma exchange (PE) is an easily applicable technique for rapid and massive removal of antibodies, and its beneficial role is well established in the management of myasthenia gravis (MG), an antibody‐mediated disorder of the neuromuscular junction. PE is useful in myasthenic crisis, in most severe forms of MG before thymectomy, in the early postoperative period, and in cases of symptom worsening during tapering or initiation of immunosuppressive therapy. Clinical efficacy varies from 55% to 100%, and improvement rarely persists for more than 4–10 weeks; thus immunosuppressive therapy has to be associated. New apheretic techniques (double filtration plasmapheresis, immunoadsorption systems with staphylococcal protein A columns or thryptophan‐polyvinyl alcohol gel columns) that allow the selective removal of IgG and anti‐AChR antibody were recently used in the management of MG with positive effects. Whether their therapeutic effect and cost effect prove more favorable than those obtained by PE still must be demonstrated.     

Retrospective analyses of clinical features and therapeutic outcomes in thymectomized patients with myasthenia gravis at Shinshu University

OBJECTIVES: Thymectomy has become recognized as an integral element in the treatment of patients with myasthenia gravis (MG). Although the incidence of elderly-onset MG has recently been increasing, there is little data demonstrating the efficacy and complications of thymectomy in this population. To clarify this point, we divided the thymectomized patients with MG into young and elderly groups, and retrospectively examined their clinical features and therapeutic outcomes. PATIENTS AND METHODS: We reviewed 57 MG patients who had been admitted to our hospital between 1988 and 2002. The patients were classified into young (younger than 60) and elderly (60 or older) groups according to the age of onset, and the therapeutic outcomes of thymectomy were evaluated using myasthenic severity scales and the duration from operation to discharge. RESULTS: Myasthenic severity scales significantly improved after thymectomy in the elderly group both with (p<0.005) and without thymoma (p<0.05) compared with before. With regard to the duration from thymectomy to discharge, no significant difference could be found between the young and elderly groups, irrespective of associated thymoma. There were no serious complications during and after thymectomy in either the young or the elderly group. CONCLUSIONS: Despite various possible complications due to aging, thymectomy should be actively considered also in the treatment of elderly MG patients because it can reliably and safely improve myasthenic symptoms in combination with immunosuppressive agents, including corticosteroid.     

Multiple ovarian cysts in a young girl with severe hypothyroidism.

Case study of a young female patient with severe hypothyroidism due to autoimmune thyroiditis and multiple ovarian cysts is reported. A 14-year 7-month-old girl presented with pelvic and abdominal pain and severe asthenia. Her last menstrual period was 10 months before presentation. Physical examination showed obesity; apathetic and flat expression; periorbital puffiness; pale, cold, dry skin and slow sustained reflexes; swelling in the hands and feet; no galactorrhea; a hardly palpable thyroid gland; and ovaries with a palpable irregular surface. Her heart rate was 90 bpm with a blood pressure within the normal range (110/70 mmHg). Laboratory findings showed severe hypothyroidism (thyroid-stimulating hormone [TSH]: 960 mIU/L), gravis macrocytic anemia, hyperfibrinogenemia, and hyperprolactinemia. Imaging examinations revealed a normal-size thyroid with irregular echogenicity, strongly hypoechogenous area at the neck ultrasonography, bilateral multilocular ovarian masses with cystic components at pelvic ultrasound and computed tomography, and both anterior and posterior pericardial effusion at echocardiography. As soon as thyroid replacement therapy was initiated, all symptoms progressively disappeared and biochemical and hormonal values normalized, while the right ovary did not decrease in size during the follow-up period. For this reason, our patient underwent right ovarian wedge resection 14 months after the initiation of medication replacement. Ovarian histological examination showed a benign ovarian cyst with extensive hemorrhage and myxedematous infiltration. It is concluded that it is important to recognize early in young girls the association between large multiple ovarian cysts and high elevated levels of TSH in order to resolve this disorder with substitutive therapy.     

Primary ovarian insufficiency: a more accurate term for premature ovarian failure

Premature ovarian failure (POF) is a disorder with a complicated clinical presentation and course that is poorly defined by its name. A more scientifically accurate term for the disorder is primary ovarian insufficiency (POI), a term that can be appropriately modified to describe the state of ovarian function. In recent years, the known aetiologies of POI have expanded, although the cause of POI in a majority of clinical cases remains undefined. The most common aetiologies should be ruled out clinically including chromosomal abnormalities, fragile X premutations and autoimmune causes. Management should be directed at symptom resolution and bone protection, but most importantly should include psychosocial support for women facing this devastating diagnosis.     

A comparative study of ocular and generalized myasthenia gravis

We compared the relations and therapeutic outcomes of ocular and generalized types of myasthenia gravis (MG) and used retrospective analysis for 65 patients with myasthenia gravis during a mean follow-up time of 30.4 months. There were 35 ocular and 30 generalized MG patients. Items of comparison included sex, age, clinical presentations, serum antibody titer, the association with thymus status, and therapeutic outcome. Of the patients with generalized MG, males were significantly older than females. Ptosis and diplopia were the most common symptoms in patients with MG, but there were no significant differences between the two types of MG. The eyelid levator muscle and lateral rectus muscle were the most commonly involved extraocular muscles in patients with MG. The associations with thymoma or thymus hyperplasia were more common in generalized MG than in ocular MG, and more common in younger than in older patients. The result of positive neostigmine test was 93.8% in all patients, but there were no significant differences between the two types of MG. Acetylcholine receptor antibody (AchRAb) presented an 81.1% positive rate and was significantly higher in generalized MG than that in ocular MG (96.2% vs 66.7%). There were no significant differences between the two types of MG regarding successful treatment strategies in both initial therapy and maintenance therapy. Only two of 16 patients had complete remissions after thymectomy. From the viewpoint of clinical presentations or from the therapeutic strategy outcome, the boundary between both types of MG seems to be vague. Both types of MG probably share the same entity in nature and the difference is just a matter of degree of severity. The benefit of thymectomy in treatment of MG needs further investigation.     

A sequence of pathologic events in a patient after thymectomy for myasthenia gravis

The case of a rare coexistence of myasthenia gravis (MG) with systemic lupus erythematosus (SLE) is described. MG was diagnosed prior to SLE which developed after thymectomy. The patient was affected by HCV viremia. Therefore, there were therapeutic problems. Metylase treatment was continued for several years and dopamine receptor agonist was effectively administered as adjunctive therapy in SLE.     

Hormonal therapy in a patient with ovarian agenesis and possible SLE: a choice to be made

Systemic lupus erythromatosus (SLE) is an autoimmune disease, which affects mainly women in the reproductive age and is influenced by hormonal changes. Therefore, hormone supplementation for patients with SLE either as contraceptives or as postmenopausal supplementation remains a controversial issue. Herein, we report a case of a 22-year-old woman with a history of ovarian agenesis, treated for several years with hormone therapy in order to reduce the risk of osteoporosis and other estrogen-deficient disorders. At the current evaluation, she met 3 of 11 diagnostic criteria for SLE along with a strong familial autoimmune predisposition. Precipitation of SLE in patients treated with hormonal therapy has been previously described. This prompted us to seek alternative drug therapies that prevent both the onset of overt SLE as well as the progression of estrogen-deficient phenomena. This unique case illustrates the dilemma of using hormone therapy in patients at risk to develop SLE and the current therapeutic alternatives.

     

Hormonal therapy in a patient with ovarian agenesis and possible SLE: a choice to be made

Systemic lupus erythromatosus (SLE) is an autoimmune disease, which affects mainly women in the reproductive age and is influenced by hormonal changes. Therefore, hormone supplementation for patients with SLE either as contraceptives or as postmenopausal supplementation remains a controversial issue. Herein, we report a case of a 22-year-old woman with a history of ovarian agenesis, treated for several years with hormone therapy in order to reduce the risk of osteoporosis and other estrogen-deficient disorders. At the current evaluation, she met 3 of 11 diagnostic criteria for SLE along with a strong familial autoimmune predisposition. Precipitation of SLE in patients treated with hormonal therapy has been previously described. This prompted us to seek alternative drug therapies that prevent both the onset of overt SLE as well as the progression of estrogen-deficient phenomena. This unique case illustrates the dilemma of using hormone therapy in patients at risk to develop SLE and the current therapeutic alternatives.     

Thymomes et maladies auto-immunes

The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection.     

Fertilit?tserhaltende Ma?nahmen bei jungen Frauen mit Autoimmunerkrankung vor zytotoxischer Therapie

In cases of severe exacerbation of autoimmune diseases (AID) cytotoxic therapy, in particular with cyclophosphamide (CYC) is needed. As the peak occurrence of such AIDs occurs in young women during the childbearing years, preservation of fertility and the hormonal function of the ovaries are an interdisciplinary challenge.For ovarian protection several options exist. Gonadotropin-releasing hormone analogues in parallel with CYC treatment seem to reduce the cytotoxic effect on the ovaries. Fertilized and unfertilized oocytes can be conserved by cryoconservation after ovarian stimulation. A relatively new strategy uses cryopreservation and autotransplantation of human ovarian tissue prior to cytotoxic therapy. As all these methods are accompanied with side-effects and possible delays in the necessary CYC treatment, a close collaboration of gynecologists and internists is needed. The decision for the optimal preservation therapy should always be based on the individual patient.     

Autoimmune hemolytic anemia as the presenting manifestation of malignant thymoma

Severe autoimmune hemolytic anemia is described as the presenting manifestation of malignant thymoma. The hemoglobin level was 5.7 g/dl, the direct IgG antiglobulin test (direct Coombs' test) was strongly positive and the indirect Coombs' test was weakly positive. Prompt remission of the hemolytic process was achieved by thymectomy combined with corticosteroid therapy; the hemoglobin level rose to 12.2 g/dl and both the direct and indirect Coombs' tests became negative. To our knowledge, this is the first case to be described in which autoimmune hemolytic anemia was the presenting manifestation of malignant thymoma. Autoimmune hemolytic anemia may be considered as a manifestation associated with malignant thymoma.     

Prognosis of patients with myasthenia gravis

AIM: To study the correlation between therapy and outcome of patients with late adult onset and ocular type myasthenia gravis (MG). METHODS: The 58 MG patients admitted to our hospitals from 1991 to 2003 were classified into juvenile (younger than 20), early adult onset (20-64) and late adult onset (65 or older) groups, or also ocular and generalized types. We evaluated their therapeutic outcomes. RESULTS: The late adult onset group consisted of 11 patients, classified as 4 ocular and 7 generalized types. There were more women than men in both the late and early adult onset groups. Anti-acetylcholine receptor (anti-AchR) antibodies were positive in all patients. Four patients had thymus lesions. Ten patients received treatment as follows: steroid therapy in 6, thymectomy in 4 and only choline-esterase (ChE) inhibitor therapy in 4 patients. However 4 patients worsened after treatment because of inadequate steroid therapy, 2 of whom experienced myasthenic crisis. On the other hand 21 patients were ocular type, of whom anti-AchR antibodies were positive in 12. They received treatments of the 21, steroid therapy was given to 12, thymectomy was performed in 4 and only ChE inhibitor therapy was given to 8 patients. One ocular type patient progressed to the generalized type. Six of 16 improved patients showed distinct recovery. CONCLUSION: In the late adult onset group careful assessment concerning timings of administration and reduction of steroid are required to avoid side effects and complications. One ocular type patient progressed to the generalized type and most patients had a good outcome, which might be related to steroid therapy.