Sever, C

Starzl, TE

Stieber, AC

English

PubMed

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33€ TRANSPLANTATION \\ t () J,No.2 HR BPM BP mmHQ PA mmHg CVP mmHg ETC02 mmH9 ICVP mmHg 100------------0-200-0-40-.. _' rt.' • "", , 0-10- I ~twDlfD l-~ ______________ __40-30-K~ ....... 0-FIGURE 4. The abrupt rise in BP is associated with calcium chloride therapy just before reperfusion of the new liver. Reperfusion is associ-ated with a drop in BP and filling pressures, but no rise in IVCP pressure, suggesting myocardial depression and/or hemorrhage as etiol-ogies, rather than impaired venous return. Time, in minutes, is indi-cated by the vertical marks on the dark horizontal line at the bottom of the CVP tracing. (HR) heart rate; (BP) blood pressure; (PAl pul-monary artery; (CVP) central venous pressure; (ETC02) end-tidal carbon dioxide; (lCVP) inferior vena ca,,'a pressure. TABLE 2. Relative magnitude of Clinical Events on Measured Pressures" Blood loss Retraction or VVB occlusion Myocardial depression IVCP 1 t -t CVP 1 -! t-GRAD " Width of arrow shaft indicates relative magnitude of event on meas-ured pressure. - indicates no effect; GRAD, IVCP - CUP. rhage, all common occurrences during OLT. Increases in IVCP suggest the former two problems as a cause, and dictate me-chanical (rather than pharmacologic) fluid or blood product therapy. (Table 2). It is intuitive that maximizing VVB pump flows should lead to higher VR, CO and blood pressure as well, while minimizing the gradient to venous return. Finally, it is possible to assess the quality of vena caval anastomosis since normal flow should yield a low gradient. We conclude that IVCP and the gradient to venous return are simple to measure and that knowledge of acute and chronic trends provides valuable adjunctive hemodynamic information during OLT. WILLIAM T. MERRITT CHARLES BEATTIE ROBERT PECK JAMES F. BURDICK ANDREW S. KLEIN Ross DICKSTEIN Departments of Anesthesiology/Critical Care Medicine The Johns Hopkins Hospital Baltimore, Maryland 21205 REFERENCES 1. Kang YG, Gelman S. Liver transplantation. In: Gelman S, ed. Anesthesia and organ transplantation. Philadelphia: Saunders, 1987. 2. Shaw BW, Martin DJ, Marquez JM, et aI. Venous bypass in clinical liver transplantation. Ann Surg 1984; 200: 524. 3. Paulsen AW, Whitten CW, Ramsay MAE, et al. Considerations for anesthetic management during veno-\'enous bypass in adult hepatic transplantation Anesth Analg 1989; 68: 489. 4. Regulation of venous return. In: Guyton AC. Jones CE, Coleman TO, eels. Circulatory physiology: cardiac output and its regula-tion. Philadelphia: Saunders, 1973: 174. Received 27 November 1989. Accepted 29 January 1990. 11-/ I fJ LIVER TRANSPLAJI.;"TATION IN PATIENTS WITH LANGERHANS' CELL HISTIOCYTOSIS! Langerhans' cell histiocytosis (LCH)* is an uncommon dis-ease, characterized by an abnormal proliferation of histiocytic cells of the dendritic family. Some patients with systemic LCH have primary liver involvement that may resemble sclerosing ! This work was supported by resean:h grants from the Veterans Administration and by Project Grant AM 29961 from the National Institutes of Health, Bethesda, MO. • Abbreviation: LCH, Langerhana' cen hystiocyt.ollis. cholangitis. Others may develop end-stage liver disease as a result of the chemotherapeutic agents used to control the primary disorder. We have performed liver transplantation in two children and one adult with this disease, the largest single-center experience in the world. A follow-up of these cases may be of special interest for two reasons. YInt, perturbations in the immune system are common in this disease. Second, light can be shed on whether immunosuppression can influence a disease with a possible autoimmune etiology. ... _---,._+------_ ... August 1990 BRIEF COMMUNICATIONS 339 Two children and one adult with a history of LCH underwent orthotopic liver transplantation at the University o( Pittsburgh since 1984. As noted, the diagnosis of the disease preceded their end-stage liver disease by 5-15 years. All three bad received some form of chemotherapy that succeeded in controlling the active disease. In two of the patients (RW. and H.C.), the end-stage liver disease was a direct result of the LCH. In the third patient (G.C.), the cirrhosis was the result of the chemotherapy treatment with methotrexate. The LCH seemed to be in com-plete remission at the time of the transplantation in the two pediatric cases, but appeared to be still active, at least in the liver (by histology) in the adult case. No tissue from pretransplant pathological studies was avail-able to us at the time of the preoperative evaluation. The patients were referred to us with a diagnosis of LCH that had been previously established in other centers. The first pediatric patient (RW.), was initially diagnosed with an eosinophilic granuloma of the skull. Subsequently he had skin in.olvement, with Langerhans' cell infiltration. At the age of 6 years, he also developed diabetes insipidus. The adult patient (H.C.) was diagnosed as having LCH on the basis of an open-lung biopsy. There is no evidence that the immunological markers were searched for. Multiple intrahepatic masses by CT scan were interpreted as LCH. The removed livers were thoroughly ex-amined for the presence of the typical Langerhans cells (below) with hematoxyilin-eosin staining as well as staining for tbe characteristic surface markers. The hilar areas and peripheral sections of the resected livers were searched for evidence of LCH. Only the adult specimen contained histiocytes that stained positively (or the 5-100 pro-tein, and all the specimens were negative (or clusters of ovoid cells bearing class II T6 surface antigen markers. All three patients underwent orthotopic liver transplantation according to a technique amply described (1). One o( the children required two retransplants due to repeated episodes of rejection. All three received the standard immunosuppressive regimen in place at the time at the University of Pittsburgh, based on cyclosporine (Sandimmune) and steroids. Rejection was treated with either a temporary increase of the steroid doses or with the antithymocyte monoclonal antibody prepa-ration OKT3 (Orthoclone). Small doses of azathioprine (lmu-ran) were added as needed for persistent low-grade rejection. All three patients did well intraoperatively and sunived for at least 1 year. The adult patient died 14 months after his transplant from pulmonary embolism following a trsumatic long bone fracture. The two pediatric patients are still alive, 5 and e~ years later. There is no evidence of recurrence of LCH in the pediatric patients. In the adult patient, there was no clinical evidence of recurrence of the disorder at the time of his death. Unfortunately, the family denied permission for autopsy, 10 no tissue was available for analysis. All three patients had repeated episodes of acute cellular rejection. The first child liven a transplant by us necessitated two retransplants, both because of uncontrollable rejection. All three patients required treatment with OKT3, two of them more than once. Langerhans' cell histiocytosis, previously known as histio-cytosis X2, is a term that covers a range of disorders character-ized by abnormal proliferation of Langerhans' histiocytic cella (3). Terms such as histiocytosis merely describe histological findings, and do not clarify the confusion that still reigns in defining the etiology and pathogenesis of these disorders (3). The classic Letterer-Siwe (4, 5) and Hand-Schuller-Christian (6,7) diseases and the eosinophilic granuloma of the bone were integrated into a single entity by the landmark research of Lichtenstein in 1953 (8). The etiology of the disorder is still unclear, although immunologic (and possibly autoimmunologic) mechanisms obviously play a role. Several hypotheses have been advanced regarding the pathogenesis of LCH (3). The characteristic Langerhans' cells are dendritic cells usually found in the skin where they act as antigen-presenting cells (9) in a different way from monocytes and macrophages (10). These cells contain the S-1OO protein (11), a calmodulin-like substance and have characteristic surface antigen markers. The Ia antigen is coded for by the HLA-DR locus (12). Its expres-sion is not influenced by microbial or lymphokine stimulation, as in macrophages (13). The T6 surface antigen may also be present on the surface membrane of the Langerhans' cell; its significance remains unclear (11). Intracytoplasmatic organ-elles called "Birbeck granules" are characteristic of these cells but their significance is unclear (14). The majority of patients are of pediatric age, although LCH has been described in adults. It is not known what causes the histiocytes to proliferate abnormally and infiltrate a variety of organs and sites. The protean nature of the disorder is evidenced by the variability of infiltration sites. When the involvement is in one place (bony or nonbony), the term eosinophilic granuloma may be used. Multifocal involvement produces the eponymous syn-dromes (Hand-Schuller-Christian or Letterer-Siwe disease). The infiltrates of histiocytes may produce "punched-out" lesions of the skull, vertebrae, and other bones (15, 16). Hy-pothalamic involvement occurs with diabetes insipidus in 25-50% of the patients (17). Extensive invasion of lymph nodes, spleen, and liver is relatively common (18-20). Bone marrow involvement, especially with thrombocytopenia (21) is partic-ularly ominous. The hepatic involvement can range from mild cholestasis to progressively more severe pictures of histiocytic infiltration and bile duct involvement-and, ultimately, scle-rosing cholangitis (22, 23). In fact, the last can eventually lead to severe fibrosis and liver failure (24,25). Primary sclerosing cholangitis has been described as associated with LCH in adults (26) and in up to 15% of the pediatric cases (27). The severity and prognosis of the disease is determined by the age of onset, extent of organ infiltration, number of involved sites, and rapidity of the progression of lesions. Staging of the disorder has been used for prognostic and therapeutic purposes (3). Although not classified as a malignancy (28), LCH has many elements in common with malignant lymphomas, especially the abnormal cellular proliferation and the immunologic changes (11, 29-32), especially thymic (33, 34) and immunoglobulin (35) abnormalities. A suppressor T cell deficiency seems to be characteristic of the disease (36, 37). LCH is a relatively infrequent disease that usually has a relatively benign course, particularly if appropriately treated. Local radiation therapy, steroids, chemotherapeutic agents-and, more recently, immunotherapy have been the treatment modalities most widely used (38-41). However, chemotherapy administered for diffuse histiocytic lesions, especially metho-trexate, may result in irreversible toxic liver damage (11). The relative decrease in the number of T suppressor cells in LCH may, in part, explain the severity and/or frequency of rejection that we observed in our patients. Unfortunately, the T4/T8 ratio is not routinely measured in our transplant popu-lation, either pre- or postoperatively, so this can be construed as mere speculation. Also, it is not clear whether successful 340 TRANSPLANTATIOS Vol. 50, No.2 treatment of the syndrome results into a restoration of the immunological parameters (including the T4(fS ratio) to nor-mal. although there is some preliminary evidence that this may occur with immunotherapy. Whether LCH itself or the therapy previously administered to treat it (in particular, immunother-apy) predisposes to rejection more severe than normally ex-pected can only be answered by better monitoring in the few cases that exist. On the other hand. there has been no recurrence of the disease in our two living patients after up to 5 years of follow-up. As immunosuppressive drugs. including cyclosporine are a part of the usual armamentarium in the treatment of LCH. it is possible that the posttransplant immunosuppression may prevent recurrence. Although the number of patients is very small and the follow up relatively brief. the absence of recur-rence is encouraging and leads us to believe that liver trans-plantation may be indicated for end-stage liver disease associ-ated with LCH. Acknowledgments. Histopathology and phenotyping of the pediatric cases was done in the Department of Pathology. Children's Hospital of Pittsburgh, by E. Yunis, M.D. and Ron Jaffe, M.D. ANDREI C. STIEBER2 CORDELIA SEVER3 THOMAS E. STARZL' The Department of Surgery The Department of Pathology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 2 For reprints, write to Andrei C. Stieber, M.D., University of Pitts-burgb School of Medicine, Department of Surgery, Division of Trans-plantation, Falk Clinic 5 C, 3601 5th Avenue, Pittsburgh, PA 15213. • Department of Surgery. 3 Department of Pathology. REFERENCES 1. Makowka L, Stieber AC, Sher L, et al. Surgical technique of orthotopic liver transplantation. Gastroenterol Clin North Am 1988; 17: 33. 2. Favara BE, Jaffe P. Pathology of Langerhans cell histiocytosis. 1987; 75. 3. Osband ME. Histiocytosis X. Hematol Oncol Clin North Am 1987; 737. 4. Letterer E. Aleukamische Retikulose (ein Betrag zu den prolifera-tiven Erkrankung des retikuloendothelial Apparatus). Frankf Ztschr Path 1924; 30: 377. 5. Siwe SA. Die Retikuloendotheliose-ein neues Krankcheitsbild unter den Hepatosplenomegalien. Ztschr Kinderh 1933; 55: 212. 6. Hand A. Polyuria and tuberculosis. Arch Pediatr 1893; 10: 673. 7. Schuller A. Ueber eigenartige Schadeldeferte in Jugendalter. Fortschr a.d. Ged d. Roentgenstrallen 1915; 23: 12. 8. Lichtenstein L. Histiocytosis X: integration of eosinophilic gran-uloma of bone, -Letterer-Siwe disease~ and "Schuller-Christian disease~ as related manifestations of a single nosologic entity. Arch Pathol 1953; 56: 84. 9. Wolff K. The Langerhans' cell. Curr Prohl Dermatol1972; 4: 79. 10. Ishii E, Watanabe S. Biochemistry and biology of the Langerhans cell. 1987; 99. 11. Favara BE, McCarthy RC, Miersu GW. Histiocytosis-X. In: Fine,old M, ed. Pathology of neoplasia in children and adoles-cents. Philadelphia: Saunders, 1986; 126. 12. Unanue ER, Beller 01, Ly CY, et a1. Antigen presentation: com-ments on its regulation and mechanisms. J Immunol 1984; 132: 1. 13. Steinman RM. Dendritic cella. Transplantation 1981; 31: 155. 14. Wolff HH. Subtle clues to diagnosis of skin disease by electron microscopy: Langerhans' cell granules in histiocytosis-X. Am J Dermatopathol 1979; 1: 77. 15. Geiser CF. The histiocytosis syndrome. Pediatr Ann 1979; 8: 54. 16. Bartholdi N, Thommesen P. Histiocytosis-X: VIII. Prognostic significance of skull lesions. Acta Radiol (Oncol] 1983; 22: 125. 17. Lieberman PH, Jones CR, Dargeon HWK, et al. A reappraisal of eosinophilic granuloma of bone, Hand-Schuller·Christian syn-drome and Letterer-Siwe syndrome. Medicine 1969; 48: 375. 18. Lipton JM_ The pathogenesis, diagnosis and treatment of histio-cytosis syndromes. Pediatr DermatoI1983; 1: 112. 19. Crocker AC. The histiocytosis syndromes. In: Vaughan VC, McKay JR, Behrman RE, Nelson WE, eds. Textbook of pediatrics. 11th ed. Philadelphia: Saunders, 1979: 1983. 20. Nesbit ME Jr, Krivit W. Histiocytosis. In: Bloom HJG et aI., eds. Cancer in children. New York: Springer 1975: 193. 21. Lucaya J. Histiocytosis-X. Am J Dis Child 1971; 121: 289. 22. Grosfeld JL. Fitzgerald JF, Wagner VM, et a1. Portal hypertension in infants and children with histiocytosis X. Am J Surg 1976; 131: 108. 23. Leblanc A., Hadchouel M, Jehan P, et al. Obstructive jaundice in children with histiocytosis X. Gastroenterol 1981; 80: 134. 24. Parker JW, Lichtenstein L. Sever hepatic involvement in chronic disseminated histiocytosis X: report of a case with necropsy. Am J Clin Pathol 1963; 40: 624. 25. Iwai M, Kashiwadani M, Okuno T, et al. Cholestatic liver disease in a 20-yr-old woman with histiocytosis X. Am J Gastroenterol 1988; 83: 164. 26. Tbompson HH, Pitt HA, Lewin KJ, et al. Sclerosing cholangitis and histiocytosis X. Gut 1984; 25: 526. 27. Sisto A, Feldman p, Garel L, et al. Primary sclerosing cholangitis in children: study of five cases and review of the literature. Pediatrics 1987; 80: 918. 28. Berry DH, Becton DL. Natural history of histiocytosis X. Hematol Oncol Clin North Am 1987; 1: 23. 29. Gotoff SP, Esterly NB. Histiocytosis. J Pediatr 1974; 85: 592. 30. Kragballe K, Zachariae H, Herlin T, et al. Histiocytosis-X: an immune deficiency disease? Studies on antibody·dependent mon-ocyte-mediated cytotoxicity. Br J Dermatol 1981; 105: 13. 31. Nesbit ME, O'Leary M, Dehner LP. et a\. Histiocytosis continued: the immune system and histiocytosis syndrome. Am J Pediatr HematolOncol 1981; 3: 141. 32. Vawter GF. Does Letterer-Siwe disease exist? Or who's not afraid of infantile histiocytosis? In: Vuksanovic MM, ed. Clinical pe-diatric oncology: research, diagnosis, treatment and prognosis of malignant tumors. Mt. Kisco, NY: Futura, 1972: 165. 33. Hamoudi AB, Newton WA, Mancer K, et al. Thymic changes in histiocytosis. Am J Clin Pathol 1982; 77: 169. 34. Ne"'"ton WA Jr, Hamoudi AB, Shannon BT. Role of the thymus in histiocytosis-X. Hematol Oncol Clin North Am 1987; 1: 63. 35. Lahey ME, Heyn R, Ladisch S, et al. Hypergammaglobulinemia in histiocytosis-X. J Pediatr 1985; 107: 572. 36. Shannon BT, Newton WA. Suppressor cell dysfunction in children with histiocytosis-X. J Clin ImmunoI1986; 6: 510. 37. Eckstein R, Huhn D, Schneider D, et al. Influence on immune function parameters in histiocytosis· X of thymostimulin. An-neimittelforschung 1985; 35: 155. 38. Cassady JR Radiation therapy in the management of histiocytosis-X. Hematol Oncol Clin North Am 1987; 1: 123. 39. Starling KA. Chemotherapy of histiocytosis-X. Hematol Oncol Clin North Am 1987; 1: 119. 40. Starling KA, Donaldson MH, Haggard ME, et al. Therapy of histiocytosis-X with vincristine, vinblastine and cyclophospha-mide. Am J Dis Child 1972; 123: 105. 41. Osband ME. Immunotherapy of histiocytosis X. Hematol Oneol Clin North Am 1987; 1: 131. Received 26 October 1989. Accepted 29 January 1990. 

Liver transplantation in patients with langerhans’ cell histiocytosis

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Liver transplantation in patients with langerhans’ cell histiocytosis

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