Thymic carcinomas and thymic neuroendocrine tumors: a tribute to Dr. Juan Rosai.

Throughout his career, Dr. Juan Rosai greatly impacted our understanding of mediastinal tumors, both as a scientist and as a teacher. This review highlights his manifold contributions in the field of thymic carcinomas and thymic neuroendocrine tumors from a historical perspective.

Surgery of the thymus in Japan.

The thymus has long been an organ of mystery. Today, it is known to be central to the construction of our immune system. I focus on the days when no one was sure what the thymus's function was. I review the Japanese literature regarding the beginnings of surgery of the thymus, especially the surgery for thymoma and thymectomy, which was performed as a treatment for myasthenia gravis.

[Forty-year experience of surgical treatment of generalized myasthenia]. / Sorokaletnii opyt khirurgicheskogo lecheniia generalizovannoi miastenii.

Forty-year experience with surgical treatment of generalized myasthenia (GM) based on 2977 cases is analyzed. Role of special methods of mediastinum examination (CT, MRT) is demonstrated, indications to thymectomy are validated. It is noted that developed diagnostic algorithm, surgical technique, management before and after surgery improved significantly immediate and long-term results. Development of clinical, immunological and morphologic criteria of thymectomy effect permitted to predict course of GM and to optimize complex therapy after surgical treatment.

[Surgery of the thymus]. / A thymus sebészete.

On the occasion of the 50th anniversary of Gyula Sebestény's death, an overview was prepared on the surgery of the thymic gland that was closely connected to his thoracic surgical activity. His results with thymectomy in myasthenia gravis were published as the second study on this topic in Europe and the first in Hungary. The early thymic surgery was based on pathological observations. Myasthenia gravis, a well-known disease for long, occurred frequently with pathological lesions of the thymus. Autopsies suggested potential causative relationship. The early period of thymic surgery was characterised by sporadic interventions and high mortality. The new period of the thymic surgery started with the American Blalock's 20 operations, and accomplished by the operative activity of Keynes including 281 thymectomies. They were followed by many European, American and Asian surgeons. Even today, there are many hotly debated topics, like indication and type of operation, prognostic factors, perioperative care, diagnosis, treatment and pathology of the thymic tumor. With fine-tuning the indication, the development of operation techniques, neurology, anaesthesiology and intensive care, imaging techniques and oncology and with introduction of new drugs the early and late results are improving. Thanks to Dr. Sebestény, Hungarian thoracic surgeons joined early the international thoracic surgical activities. Currently in Hungary there are two major centers for myasthenia gravis surgery, and all important thoracic surgical departments in the country treat thymic tumor cases.

Cellular immunology in a historical perspective.

Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems are distinct from each other in humans - thymus-dependent cell-mediated immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus lymphoid organ of rabbits, like the bursa of Fabricius, represents a central lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that phagocytosis killing of catalase-positive microorganisms employ oxidative burst. Bone marrow transplantation (BMT) proved life saving in severe combined immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a complicating aplastic anemia launching BMT as a treatment of many diseases. Now 75 fatal diseases have been cured by myeloablative BMT. BMT also cured experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell) transplants cured these diseases. Autoimmune diseases and lethal glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2-year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem cells (stromal cells) was effective treatment for a form of collagen-vascular disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an opsonin that activates the complement system when mutated and at low levels in blood, opens a door to frequent infections throughout childhood and adult life. This new immunodeficiency is based on genetic mutations that involve a native defense system.