Ann Thorac Surg 2008;86:e7-e8. doi:10.1016/j.athoracsur.2008.07.062
© 2008 The Society of Thoracic Surgeons
Case Reports
Sirolimus Ameliorated Post Lung Transplant Chylothorax in Lymphangioleiomyomatosis
Toshiaki Ohara, MDa,
Takahiro Oto, MDa,*,
Kentaro Miyoshi, MDa,
Hiroyuki Tao, MDa,
Masaomi Yamane, MDa,
Shinichi Toyooka, MDa,
Megumi Okazaki, RNa,
Hiroshi Date, MDb,
Yoshifumi Sano, MDa
a Department of Thoracic Surgery, Okayama University Hospital, Okayama, Japan
b Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
Accepted for publication July 9, 2008.
* Address correspondence to Dr Oto, Department of Thoracic Surgery, Okayama University Hospital, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan (Email: oto{at}md.okayama-u.ac.jp).
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Abstract
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We report a successful case of sirolimus treatment for chylous pleural and peritoneal effusions of lymphangioleiomyomatosis after lung transplantation. A 32-year-old woman underwent living donor lung transplantation. Persistent chylous pleural and peritoneal effusions were seen postoperatively. Pleurodesis by intrathoracic injection of OK-432, minomycin, and somatostatine analog failed to control chylous effusions. However, sirolimus treatment reduced the amount of chylous drainage and improved both chylous pleural and peritoneal effusions.
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Introduction
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Lymphangioleiomyomatosis (LAM) is a rare disease characterized by abnormal proliferation of abnormal smooth-muscle cells leading to obstruction of airways and lymphatics (eg, chylous pleural and peritoneal effusions) [1]. Lung transplantation is an option for patients with end-stage LAM, but chylous pleural and peritoneal effusions remain problematic even after lung transplantation [2]. Chylous effusion is seen in 10% to 25% of patients with LAM [1, 3–5]. Intravenous hyperalimentation and fasting and pleurodesis have been performed to treat chylous effusions in patients with LAM. In the present case, sirolimus therapy successfully controlled post-transplant chylous effusion after failure of conventional therapies.
A 32-year-old woman (height, 156 cm; weight, 47 kg) underwent bilateral living donor lung transplantation due to end-stage LAM. After bilateral pneumonectomy under cardiopulmonary bypass support, bilateral living donor lung transplantation was performed using two lobes from two healthy donors. After transplantation, persistent chylous pleural and peritoneal effusions with high levels of triglyceride (2,000 to 3,000 mL/day) were seen (Fig 1A), and prolonged bilateral pleural drainage was required along with intravenous hyperalimentation and fasting (Fig 2). Despite repeated pleurodesis with the combination of OK-432 and minomycin or the single use of somatostatine analog (100 mg/day), the amount of chylous drainage was not decreased. Therefore, oral administration of sirolimus (1 mg/day) was initiated 66 days after transplantation. After the initiation of sirolimus therapy, the amount of chylous drainage was decreased (Fig 2) and bilateral chest tubes were removed 35 days later. An abdominal computed tomographic scan also showed reduced chylous peritoneal effusions after initiation of the sirolimus therapy (Fig 1B). No obvious side effects of sirolimus therapy, including bronchial anastomotic problems, were seen.
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Fig 1. Abdominal computed tomographic scan shows reduced chylous peritoneal effusions after initiation of the sirolimus therapy. (A) Before and (B) after sirolimus therapy.
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Fig 2. Amount of total drainage of chylous pleural effusion was reduced after initiation of sirolimus therapy. (Arrows = pleurodesis with minomycin only, OK-432 only, and combined use of minomycin and OK-432; SSTN = somatostatine analog administration.)
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Comment
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Lymphangioleiomyomatosis is a rare disease associated with loss of function of the tumor suppressor gene tuberous sclerosis (TSC)1 and TSC2, resulting in constitutive activation of the mammalian target of rapamycin [6, 7]. Loss of TSC2 GTPase Activating Protein activity or disruption of the TSC1/TSC2 complex deregulates ribosomal protein S6 kinase 1 activation, which leads to abnormal cell proliferation [6].
Recently, sirolimus, a specific S6 kinase 1 inhibitor that blocks growth factor-driven cell proliferation, was introduced as a therapy for lung transplant recipients with LAM [8]. Because sirolimus, a mammalian target of rapamycin inhibitor, can correct cellular abnormalities produced by loss of function of TSC1/2, it could prevent LAM development and chylous production.
The role of sirolimus administration for angiomyolipoma in tuberous sclerosis complex or LAM has been described previously [7]. In that case, prolonged bilateral pleural drainage was required after transplantation due to a high amount of chylous pleural effusion (2,000 to 3,000 mL/day), despite treatment with conventional therapies. A role for sirolimus in routine post-lung transplant immunosuppression for LAM [9] or for recurrent LAM after lung transplant has also been suggested [10]. However, using sirolimus for patients waiting for lung transplant or for patients in the early post-transplant period is not recommended due to its potential risk of inhibition of bronchial anastomotic healing [11].
Even a small amount of pleural effusion occupying the pleural spaces may affect the recipient's lung function in lobar lung transplantation. Therefore, controlling the production of pleural effusion is more important in lobar lung transplantation than in whole lung transplantation. The present study showed an association between sirolimus therapy and reduced chylous pleural and peritoneal effusions in a lobar lung transplant patient. Sirolimus may control chylous effusions in patients with LAM before and after lung transplant.
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References
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- Corrin B, Liebow AA, Friedman PJ. Pulmonary lymphangiomyomatosis Am J Pathol 1975;79:348-392.[Medline]
- Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphagioleiomyomatosis N Engl J Med 1996;335:1275-1280.[Medline]
- Urban T, Kuttenn F, Gompel A, et al. Pulmonary lymphangiomyomatosis. Follow-up and long-term outcome with antiestrogen therapy; a report of eight cases. Chest 1992;102:472-476.
- Chu SC, Horiba K, Usuki J, et al. With lymphangioleiomyomatosis comprehensive evaluation of 35 patients Chest 1999;115:1041-1052.[Medline]
- Ryu JH, Doerr CH, Fisher SD, et al. Chylothorax in lymphangioleiomyomatosis Chest 2003;123:623-627.[Medline]
- Goncharova EA, Goncharov DA, Spaits M, et al. Abnormal growth of smooth muscle-like cells in lymphangioleiomytosis role for tumor suppressor TSC2 Am J Respir Cell Mol Biol 2006;34:561-572.[Abstract/Free Full Text]
- Bissler JJ, McCormack FX, Young LR, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis N Engl J Med 2008;358:140-151.[Medline]
- Dennis PB, Fumagalli S, Thomas G, et al. Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degradation Curr Opin Genet Dev 1999;9:49-54.[Medline]
- Morton JM, McLean C, Booth SS, et al. Regression of pulmonary lymphangioleiomyomatosis (PLAM)-associated retroperitoneal angiomyolipoma post-lung transplantation with rapamycin treatment J Heart Lung Transplant 2008;27:462-465.[Medline]
- Sugimoto R, Nakao A, Yamane M, et al. Sirolimus ameliorated clinical symptoms of recurrent lymphangiomyomatosis (LAM) after living-donor lobar lung transplantation J Heart Lung Transplant 2008;27:921-924.[Medline]
- Groetzner J, Kur F, Spelsberg F, et al. Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression J Heart Lung Transplant 2004;23:632-638.[Medline]
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Abstract
Introduction
