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Successful Factor XIII Administration for Persistent Chylothorax After Lung Transplantation for Lymphangioleiomyomatosis

2009; Elsevier BV; Volume: 88; Issue: 3 Linguagem: Inglês

10.1016/j.athoracsur.2009.01.048

1552-6259

Norihisa Shigemura, Tomohiro Kawamura, Masato Minami, Noriyoshi Sawabata, Masayoshi Inoue, Tomoki Utsumi, Tomoyuki Nakagiri, Goro Matsumiya, Yoshiki Sawa, Meinoshin Okumura,

Eosinophilic Disorders and Syndromes

Lung transplantation has emerged as a viable treatment option for patients with end-stage lymphangioleiomyomatosis (LAM), and therapeutic outcome results reported thus far have been satisfactory. However, persisting chylothorax after transplantation for LAM remains a challenging problem, and the optimal management has not been decided. We present the case with persistent chylothorax after lung transplantation for LAM, in which the intravenous administration of a tissue repair factor (human factor XIII) resulted in complete resolution of chylous effusion without performing additional invasive treatments, leading to a successful transplant outcome. Lung transplantation has emerged as a viable treatment option for patients with end-stage lymphangioleiomyomatosis (LAM), and therapeutic outcome results reported thus far have been satisfactory. However, persisting chylothorax after transplantation for LAM remains a challenging problem, and the optimal management has not been decided. We present the case with persistent chylothorax after lung transplantation for LAM, in which the intravenous administration of a tissue repair factor (human factor XIII) resulted in complete resolution of chylous effusion without performing additional invasive treatments, leading to a successful transplant outcome. Chylothorax is a well-known complication of lymphangioleiomyomatosis (LAM) in both preoperative and postoperative lung transplantation cases [1Ryu J.H. Doerr C.H. Fisher S.D. Olson E.J. Sahn S.A. Chylothorax in lymphangioleiomyomatosis.Chest. 2003; 123: 623-627Crossref PubMed Scopus (102) Google Scholar, 2Pechet T.T. Meyers B.F. Guthrie T.J. Battafarano R.J. Trulock E.P. Cooper J.D. Patterson G.A. Lung transplantation for lymphangioleiomyomatosis.J Heart Lung Transplant. 2004; 23: 301-308Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar]. Without adequate treatment for postoperative chylothorax, it can become a critical problem and cause an unsuccessful transplant outcome. However, most conventional treatment modalities have some risks and limitations. Herein, we describe a novel therapy for persistent chylothorax after lung transplantation for LAM that uses a tissue repair factor (human factor XIII) that may be useful for complete resolution of chylous effusion leading to a successful transplant outcome. A 35-year-old woman diagnosed with end-stage LAM was referred to our center for lung transplantation in April 2008. Lymphangioleiomyomatosis had been diagnosed 5 years before because of bilateral chylothoraxes, which required tube thoracostomy placement in the right pleural space and pleurodesis in the left pleural space. At the time of listing, she had severely limited pulmonary reserve with a forced vital capacity of 1.71 L (59% of predicted), a forced expiratory volume in 1 second of 0.93 L (38% of predicted), and a diffuse capacity for carbon monoxide of 3.57 L/min/kpa (26% of predicted). Furthermore, blood gas on room air showed Po2 of 48 mm Hg and Pco2 of 30 mm Hg. Six-minute walk results were 920 feet on 4 L of oxygen through a nasal cannula with significant desaturation to 73%. A chest radiograph on admission is shown in Figure 1. During the following months, the patient had a progressive decline in pulmonary status, after which a donor became available and she underwent right single-lung transplantation. During that operation, moderate symphysis was noted in the native right chest cavity with a mild amount of chylous effusion (300 mL), which is commonly foun in LAM cases. The lung transplant surgery was completed uneventfully, and the patient was breathing spontaneously and was extubated on postoperative day 3. From the first postoperative day, a moderate amount of pleural effusion was observed from the right chest tubes. When the patient re-started oral intake, the effusion showed an evident conversion to chylous effusion on the same side (500 mL/day). We initially provided conservative management, which included total parenteral nutrition with no oral intake and aggressive diuresis, and the amount of pleural effusion decreased gradually, although it remained greater than 200 mL/day. On postoperative day 23, we commenced intravenous injections of human recombinant factor XIII (Fibrogammin HS [Aventis Behring, Marburg, Germany]) 12 mL per day for the following 5 days, as recommended by the manufacturer. The pre-treatment value of factor XIII in plasma was 75% (normal, 70% to 100%). Twenty-four hours later, a significant decrease in chylous pleural effusion was noted, and several days after completing administration, the chest tubes were removed and a chest roentgenogram was taken at that time, which revealed excellent expansion of the lung. No recurrence of chylous effusion within the next 6 months of follow-up was observed. Chest radiographs 1 week after patient was off chest drain and 6 months after transplantation are shown in Figures 2A and 2B. At the time of writing, 8 months after transplantation, the patient was leading an independent, active lifestyle and was able to perform normal activities of daily living without dyspnea or the need for oxygen. Recent pulmonary function tests showed a forced vital capacity of 1.85 L (65% of predicted) and a forced expiratory volume in 1 second of 1.44 L (78% of predicted). Lymphangioleiomyomatosis is a rare destructive lung disease characterized by an abnormal proliferation of smooth muscle-like cells (LAM cells) in the lung and along the axial lymphatics, which leads to progressive, diffuse, and cystic changes in the lung parenchyma, obstruction of the airways and lymphatics, and loss of pulmonary function. Lung transplantation has emerged as a viable treatment option for patients with end-stage LAM, and therapeutic outcome results reported thus far have been satisfactory [1Ryu J.H. Doerr C.H. Fisher S.D. Olson E.J. Sahn S.A. Chylothorax in lymphangioleiomyomatosis.Chest. 2003; 123: 623-627Crossref PubMed Scopus (102) Google Scholar, 2Pechet T.T. Meyers B.F. Guthrie T.J. Battafarano R.J. Trulock E.P. Cooper J.D. Patterson G.A. Lung transplantation for lymphangioleiomyomatosis.J Heart Lung Transplant. 2004; 23: 301-308Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar]. However, persisting chylothorax after transplantation for LAM remains a challenging problem, and the optimal management has not been decided, although it is a well-described, yet uncommon complication. Furthermore, this complication, if treated inadequately, can severely affect transplant outcome. In general, postoperative chylothorax causes nutritional deficiencies, respiratory dysfunction, and dehydration, while it also affects immunosuppression, thus increasing vulnerability for infections [3Fahimi H. Casselman F.P. Mariani M.A. Boven W.J. Knaepen P.J. Swieten H.A. Current management of postoperative chylothorax.Ann Thorax Surg. 2001; 71: 448-451Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. After transplantation and the use of many of the available immunosuppressive agents, chylothorax may result in a fatal outcome. Thus, the condition requires prompt action and thoracic surgical input, as well as transplant expertise. Treatment modalities for chylothorax generally include a total parenteral or low-fat diet and chest tube drainage, followed by chemical or mechanical pleurodesis. In addition, more aggressive surgical options, such as thoracic duct ligation or clipping have also been effectively used [4Dauriat G. Brugiere O. Mal H. Camuset J. Castier Y. Leseche G. Fournier M. Refractory chylothorax after lung transplantation for lymphangioleiomyomatosis.J Thorac Cardiovasc Surg. 2003; 126: 875-877Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 5Hamdan M.A. Gaeta M.L. Ocreotide and low-fat breast milk in postoperative chylothorax.Ann Thorac Surg. 2004; 77: 2215-2217Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 6Christodoulou M. Ris H.B. Pezzetta E. Video-assisted right supradiaphragmatic thoracic duct ligation for non-traumatic recurrent chylothorax.Eur J Cardiothorac Surg. 2006; 29: 810-814Crossref PubMed Scopus (38) Google Scholar]. Also, Fremont and colleagues [7Fremont R.D. Milstone A.P. Light R.W. Ninan M. Chylothoraces after lung transplantation for lymphangioleiomyomatosis: review of the literature and utilization of a pleurovenous shunt.J Heart Lung Transplant. 2007; 26: 953-955Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar] recently reported the interesting option of using a pleurovenous shunt for refractory chylous effusions, which can be placed without difficulty. Unfortunately, medical management alone is frequently unsuccessful or provides only minor or inconsistent benefits. Pleurodesis may damage the transplanted organ, leading to worsened pulmonary function, despite invasive treatment. Surgical options, even if they are less invasive by being performed under video-assisted thoracic surgery, may be the last resort after transplantation, as they carry their own risk. Pleurovenous shunt placement may be a promising and less invasive intervention, although a number of complications such as bleeding, air embolism, infection, and pump occlusion, as well as shunt failure as a long-term complication, can accompany that procedure. When considering the best treatment for chylothorax after lung transplantation for LAM, we suggest that the original disease characteristics be taken into consideration, as well as the special conditions after transplantation. Lymphangioleiomyomatosis is a destructive disease [8Johnson S.R. Lymphangioleiomyomatosis.Eur Respir J. 2006; 27: 1056-1065Crossref PubMed Scopus (183) Google Scholar], and the capacity for tissue repair and remodeling after injury may be limited and insufficient in affected patients. In general, the role of factor XIII in coagulation and clot stabilization has been well established based on accumulated evidence [9Lorand L. Factor XIII: structure, activation, and interactions with fibrinogen and fibrin.Ann NY Acad Sci. 2001; 936: 291-311Crossref PubMed Scopus (191) Google Scholar]. It has been reported that this factor contributes to reducing chylous effusion after pediatric cardiac surgery only for the first 24 hours after treatment, whereas it did not alter the further clinical outcome such as chest tube drainage during the 3 days or time to chest tube removal [10Schroth M. Meibner U. Cesnjevar R. Weyand M. Singer H. Rascher W. Klinge J. Recombinant factor XIII reduces severe pleural effusion in children after open-heart surgery.Pediatr Cardiol. 2006; 27: 56-60Crossref PubMed Scopus (15) Google Scholar]. In addition, human factor XIII is a transglutaminase that plays a pivotal role in wound healing and repair process with its proliferative and anti-apoptotic effects on endothelial and epithelial cells [11Carlo E. Goebell H. Dignass A.U. Factor XIII modulates intestinal epithelial wound healing in vitro.Scand J Gastroenterol. 1999; 34: 485-490Crossref PubMed Scopus (31) Google Scholar]. Although the detailed mechanisms of the factor XIII-mediated effects on tissue repair have not been fully elucidated, these findings, taken together, seem to show that in addition to clot stabilization, factor XIII administration may compensate for lack of the capacity for tissue repair in LAM, leading to the successful, long-lasting resolution of chylothorax after transplantation. It is reasonable to assume that a single administration of factor XIII has some limitations, particularly in patients with high-output chylous effusion. In such cases, agents such as somatostatin (Sandostatin [Novartis Pharmaceuticals, East Hanover, NJ]), which may help to diminish lymph flow through the inhibition of pituitary and gastrointestinal hormone release and reductions in gastrointestinal blood flow and hepatic venous pressure [12Kelly R.F. Shumway S.J. Conservative management of postoperative chylothorax using Somatostatin.Ann Thorac Surg. 2000; 69: 1944-1945Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar] should be used together with factor XIII. Furthermore, in a personal communication, the authors learned that a combined administration of somatostatin and factor XIII was useful in a case with postoperative high-output chylothorax after aortic surgery. Administration of factor XIII, as an option for use in conservative management of chylothorax, is a relatively new concept. It may be of particular benefit in susceptible or unstable situations, such as after transplantation. Persistent chylothorax after lung transplantation for LAM may be the result of injuries to the lymphatic ducts followed by a limited capacity for tissue repair, conditions often seen in patients with this destructive disease. Therefore, the present results showing that supplementation with factor XIII, a key factor in wound healing and tissue repair, as well as clot stabilization, may provide a mechanistic explanation for enhanced repair of damaged lymphatic tissues, leading to an effective treatment for chylothorax occurring in LAM patients. This supplementation is a noninvasive treatment that makes it possible to avoid damaging the transplanted organs is possibly the most important point; thus it is a useful adjunct to conservative treatment in the special situations after transplantation.