A case of chylothorax treated curatively with Sapylin, a streptococcus preparation

A case of chylothorax treated curatively with Sapylin, a streptococcus preparation first-author corresp ‡Corresponding Author ‡Corresponding Author †E-mail:xufeng99@yahoo.com †E-mail:xufeng99@yahoo.com xufeng99@yahoo.com Department of Respiratory Diseases, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Department of Respiratory Diseases, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Chylothorax is an uncommon disease where fatty fluid accumulates within the chest cavity. Conservative management, including repeated thoracentesis or pleurodesis, seems to be suitable to most cases. Herein, we present a case of efficacious pleurodesis by intrapleural injection of Sapylin, a streptococcus preparation, for the treatment of chylothorax. A 52-year-old non-smoking female farmer was diagnosed as idiopathic chylothorax after we ruled out possible causes including chest trauma, lymphoma, lung cancer, filariasis, tuberculosis, and etc. Two-time intra-thoracic injection of 3 Klinische Einheit (KE) Sapylin achieved rapid and effective control of chylothorax with no severe side effects. Sapylin may facilitate pleurodesis by producing a strong inflammatory response. Chylothorax Sapylin Streptococcus preparation INTRODUCTION 1 Chylothorax refers to the presence of fatty fluid (chyle) with increased triglyceride levels in the pleural space, secondary to leakage from the thoracic duct or one of its main tributaries. Patients with chylothorax can be normally treated by conservative therapy or surgery. Some agents such as bleomycin, talc, and tetracycline have been used in pleurodesis (Dikensoy and Light, 2005 2005 ; Tan et al., 2006 2006 ). However, the streptococcus preparation was rarely reported in the treatment for chylothorax. Here, we present a case of efficacious pleurodesis by intrapleural injection of Sapylin, a streptococcus preparation, in a patient with chylothorax. CASE REPORT 1 A 52-year-old non-smoking female farmer was hospitalized because of chest distress for 4 months. She had no cough, bloody sputum, chest pain, fever and also no history of chest trauma. Physical examination showed the respiratory sound of right lung degraded remarkably. Ultrasound and X-ray examination showed massive right pleural effusions. Thoracentesis was performed and the level of triglyceride of pleural fluid was 1 104 mg/dl whereas cholesterol concentration was 64 mg/dl. Our findings indicate a chylothorax. Pulmonary computed tomography (CT) scan, pleural biopsy and brochoscopy revealed no important finding. Other examinations including schistosoma antibody, cysticercus specific antibody, acid-fast bacilli of sputum and microfilaria of peripheral blood had no positive results. “Idiopathic chylothorax” was designated after we ruled out all possible causes including chest trauma, lymphoma, lung cancer, filariasis, tuberculosis, and etc. The chest tube was inserted and fat-free diet was given for 2 weeks. But these managements seemed to have no effect and draining volume of chyle remained more than 1000 ml daily. Therefore, 3 Klinische Einheit (KE) of Sapylin with 50 mg lidocaine and 10 mg dexamethasone in 50 ml of physiological saline was injected into the right pectoral cavity via chest tube. The chest tube was clamped and the patient was repositioned every 30 min for 4 h. The volume of chylous fluid decreased gradually from 1 000 ml to 100 ml daily within 5 d. An additional 3 KE of Sapylin was administered subsequently. There was no chyle again after the second injection. She was discharged after 3 d of observation and the chest radiograph revealed no effusion (Fig. 1 1 ). Ultrasound examination also revealed no reaccumulation of chylothorax during 6 months follow-up. DISCUSSION 1 Chylothorax is a relatively uncommon disorder whose etiopathogenisis is divided into traumatic chylothorax and non-traumatic chylothorax, and the latter includes tumor, filariasis, tuberculosis, and etc. However, some cases still have no clear cause, so idio-chylothora is designated. Patients with chylothorax can be treated by conservative therapy or surgery. Sometimes radiotherapy may promote resolution of chylothorax and should be used in patients with malignant chylothorax who are not surgical candidates (Duffy et al., 2005 2005 ). Conservative management, including repeated thoracentesis or pleurodesis, seems to be suitable to most cases (Jimenez et al., 2007 2007 ). Pleurodesis has been successfully implemented using various agents such as bleomycin, talc, tetracycline, thrombin, and etc. However, other local and systemic side effects, such as pulmonary fibrosis with bleomycin, make most sclerosants unsatisfactory forms of treatment (Laranne et al., 2002 2002 ). Sapylin, made in Lukang Pharmaceutical Co., China, is a lyophilized biological preparation of streptococcus (strain 722) treated with penicillin. 1 KE of Sapylin contains 0.1 mg of dried cocci. Sapylin is an analogue of OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo), which has been used in Japan primarily as immunotherapy for malignant tumors and lymphangiomas. The streptococcus preparations can activate natural killer cells and T cells, as well as inducing the production of cytokines such as tumor necrosis factor, interleukin-6, vascular endothelial growth factor and transforming growth factor β 1 . Therefore, the intrathoracic injection of these agents promotes the development of fibrin clots, and this is thought to facilitate pleurodes (Ogita et al., 1996 1996 ; Fujino et al., 2003 2003 ). Sapylin/OK-432 produces an inflammatory reaction leading to the destruction of the epithelial lining and the subsequent sclerosis and cicatricial contraction of the lesion, too. It is reported that after continuous aspiration of pleural effusion and the infusion of 10 KE of OK-432 into the pleural cavity, the chylothorax of lymphangioleiomyomatosis disappeared (Adachi et al., 2004 2004 ). In addition, patients with chylothorax due to the right pulmonary transplantation and lung cancer were successfully treated by intra-thoracic infusion with streptococcus preparations (Koga et al., 1999 1999 ; Fujimura and Kondo, 2000 2000 ). Shimizu et al.( 1994 1994 ) demonstrated that six adult patients with chylothorax after chest surgery showed an improvement without the need for thoracic duct ligation by intra-pleural injection of 0.1~0.5 mg of OK-432. In the present report, the patient with idiopathic chylothorax was successfully controlled by two-time intra-thoracic infusion of 3 KE Sapylin. Sapylin injection achieved rapid and effective control of pleural effusions with no severe adverse effects. The common side effects of streptococcus preparations reported in previous studies were fever and a local inflammatory reaction. Pleurodesis by intra-pleural injection of OK-432 was even used for the treatment of fetal chylothorax, showing no teratogenicity or fetal toxicity (Tsukihara et al., 2004 2004 ). In summary, pleurodesis with intrapleural injection of Sapylin, a streptococcus preparation, could be an effective treatment for chylothorax. However, more cases in randomized studies need to be further observed. References H Adachi , T Hashimoto , M Komiyama , Y Miyao , A Sudou , H Nakamura , T Matuoka . Lymphangioleiomyomatosis (LAM) causing chylothorax . Nihon Kokyuki Gakkai Zasshi , 2004 . 42 ( 1 ): 80 - 83 . (in Japanese) 14768369 . Lymphangioleiomyomatosis (LAM) causing chylothorax O Dikensoy , RW Light . Alternative widely available, inexpensive agents for pleurodesis . Curr Opin Pulm Med , 2005 . 11 ( 4 ): 340 - 344 . 15928503 DOI: 10.1097/01.mcp.0000166587.24127.91 http://doi.org/10.1097/01.mcp.0000166587.24127.91 . Alternative widely available, inexpensive agents for pleurodesis BM Duffy , R Manon , RR Patel , JS Welsh . A case of Gorham’s disease with chylothorax treated curatively with radiation therapy . Clin Med Res , 2005 . 3 ( 2 ): 83 - 86 . 16012125 . A case of Gorham’s disease with chylothorax treated curatively with radiation therapy S Fujimura , T Kondo . The lung transplantation has come to be done in Japan . Kyobu Geka , 2000 . 53 ( 12 ): 986 - 991 . (in Japanese) 11079300 . The lung transplantation has come to be done in Japan A Fujino , Y Moriya , Y Morikawa , K Hoshino , T Watanabe , N Shimojima , M Kitajima . A role of cytokines in OK-432 injection therapy for cystic lymphangioma: an approach to the mechanism . J Pediatr Surg , 2003 . 38 ( 12 ): 1806 - 1809 . 14666473 DOI: 10.1016/j.jpedsurg.2003.08.041 http://doi.org/10.1016/j.jpedsurg.2003.08.041 . A role of cytokines in OK-432 injection therapy for cystic lymphangioma: an approach to the mechanism CA Jimenez , AD Mhatre , CH Martinez , GA Eapen , A Onn , RC Morice . Use of indwelling pleural catheter for the management of recurrent chylothorax in patients with cancer . Chest , 2007 . 132 ( 5 ): 1584 - 1590 . 17890482 DOI: 10.1378/chest.06-2141 http://doi.org/10.1378/chest.06-2141 . Use of indwelling pleural catheter for the management of recurrent chylothorax in patients with cancer K Koga , Y Mita , K Dobashi , T Masuo , M Aihara , Y Shimizu , Y Umegae , M Mori . Lung cancer with chylothorax successfully treated by chemical pleurodesis with OK-432 . Nihon Kokyuki Gakkai Zasshi , 1999 . 37 ( 8 ): 627 - 630 . (in Japanese) 10496102 . Lung cancer with chylothorax successfully treated by chemical pleurodesis with OK-432 J Laranne , L Keshi-Nisula , R Rautio , M Rautiainen , M Airaksinen . OK-432 (Picibanil) therapy for lymphangiomas in children . Eur Arch Otorhinolaryngol , 2002 . 259 ( 5 ): 274 - 278 . 12107533 DOI: 10.1007/s00405-001-0438-6 http://doi.org/10.1007/s00405-001-0438-6 . OK-432 (Picibanil) therapy for lymphangiomas in children S Ogita , T Tsuto , K Nakamura , E Deguchi , K Tokiwa , N Iwai . OK-432 therapy for lymphangioma in children: why and how does it work? . J Pediatr Surg , 1996 . 31 ( 4 ): 477 - 480 . 8801295 DOI: 10.1016/S0022-3468(96)90478-9 http://doi.org/10.1016/S0022-3468(96)90478-9 . OK-432 therapy for lymphangioma in children: why and how does it work? J Shimizu , Y Hayashi , M Oda , K Morita , Y Arano , S Nagao , S Murakami , H Urayama , Y Watanabe . Treatment of postoperative chylothorax by pleurodesis with the streptococcal preparation OK-432 . Thorac Cardiovasc Surg , 1994 . 42 ( 4 ): 233 - 236 . 7825162 . Treatment of postoperative chylothorax by pleurodesis with the streptococcal preparation OK-432 C Tan , A Sedrakyan , J Browne , S Swift , T Treasure . The evidence on the effectiveness of management for malignant pleural effusion: a systematic review . Eur J Cardiothorac Surg , 2006 . 29 ( 5 ): 829 - 838 . 16626967 DOI: 10.1016/j.ejcts.2005.12.025 http://doi.org/10.1016/j.ejcts.2005.12.025 . The evidence on the effectiveness of management for malignant pleural effusion: a systematic review A Tsukihara , M Tanemura , Y Suzuki , T Sato , T Tanaka , K Suzumori . Reduction of pleural effusion by OK-432 in a fetus complicated with congenital hydrothorax . Fetal Diagn Ther , 2004 . 19 ( 4 ): 327 - 331 . 15192291 DOI: 10.1159/000077960 http://doi.org/10.1159/000077960 . Reduction of pleural effusion by OK-432 in a fetus complicated with congenital hydrothorax 10.1631/jzus.2007.B0885 Project (No. 30500229) supported partly by the National Natural Science Foundation of China 2007-09-24 2007-11-09 2022-01-05 Copyright © 2007, Journal of Zhejiang University Science 2007 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 12 08