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(Chest. 2000;117:902-905.)
© 2000 American College of Chest Physicians

Conservative Treatment of Postsurgical Lymphatic Leaks With Somatostatin-14*

Jean-Marie Collard, MD; Pierre-François Laterre, MD; Freddy Boemer, MD; Marc Reynaert, MD and Robert Ponlot, MD

* From the Departments of Surgery (Drs. Collard and Ponlot) and Intensive Care (Drs. Laterre and Reynaert), St-Luc Academic Hospital, Brussels, and Department of Internal Medicine (Dr. Boemer), Queen Astrid Hospital, Malmedy, Belgium.

Correspondence to: J.M. Collard, MD, Department of Surgery, St-Luc Academic Hospital, Hippocrate Avenue, 10, B–1200 Brussels, Belgium; e-mail: Collard{at}chir.ucl.ac.be


   Abstract
TOP
 Abstract
Report of Cases
 Discussion
 References
 
Successful management of lymphatic leaks by continuous IV administration of somatostatin was first reported by Ulibarri and coworkers in Spain,1 and more recently by authors from Italy2 and Switzerland.3 The present article reports the clinical history of two patients in whom postsurgical lymphatic leak was successfully treated after the administration of either somatostatin-14 alone (case 1) or combined somatostatin-14 and total parenteral nutrition (TPN; case 2). Although further pathophysiologic studies are needed for the elucidation of its mechanisms of action, somatostatin-14 seems to be an intriguing therapy against postsurgical lymphatic leaks that may make potentially risky transthoracic reoperation unnecessary.

Key Words: fistula • somatostatin • thoracic duct


   Report of Cases
TOP
 Abstract
 Report of Cases
Discussion
 References
 
Case 1
A 54-year-old man with multiple mediastinal masses had been admitted for pretherapeutic check-ups in the Department of Internal Medicine. He underwent conventional mediastinoscopy through a small suprasternal incision in the neck. Several macro biopsies of the masses were taken for histologic examination. A polyvinyl drain was left in the anterosuperior mediastinum for drainage. The day after, drainage outflow reached 210 mL of lymphocyte-rich fluid. Despite the fact that the patient was fasting and being maintained on TPN, injury to the thoracic duct was suspected as drainage outflow progressively increased (Fig 1 ). Therefore, it was decided to clip the lower segment of the thoracic duct thoracoscopically.4 Under general anesthesia, four trocars were inserted through the right chest wall, one for the optical device, one for a lung retractor, and two for working instruments or a clip applier. The thoracic duct was identified, lying between the right azygous vein and the descending aorta just in front of the spine. After division of the duct between metal clips, a chest tube was left in the right chest cavity for drainage. The day after, fluid outflow through the cervical drain dropped from 940 to 330 mL/d without any further decrease during the next days (350 mL/d 7 days after the thoracoscopy). Persistent weeping was ascribed to injury to paratracheal lymphatic vessels draining pulmonary-in-origin lymphatic fluid.5 6 Therefore, somatostatin-14 (UCB S.A. Pharma sector; Braine-L’Alleud, Belgium) was administered by continuous IV infusion at the doseage of 6 mg/d. Cervical drain outflow dropped from 400 to 90 mL/d within 36 h, and it reduced progressively to 3 mL/d within a 5-day period. Somatostatin therapy was maintained for an additional 6-day period, ie, at the doseage of 6 mg/d for 4 days and of 3 mg/d for the last 2 days, after which the drug was discontinued, and the cervical drain was removed. Measurement of the glucose blood level four times per day did not show any major disturbance in the glucose regulatory mechanisms.



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  		Figure 1.. Lymphatic fluid outflow profile after substernal mediastinoscopy in case 1, showing an initial outflow reduction after thoracoscopic division of the thoracic duct between metal clips (black boxes), and a second drop after somatostin-14 administration (hatched boxes).

 
Case 2
A 56-year-old man with cancer arising in Barrett’s esophagus7 underwent transthoracic esophagectomy and gastric pull-up to the neck.8 Esophagectomy included resection of the esophageal tube en bloc with the vagus nerves, the thoracic duct, and the right azygous vein.9 The thoracic duct was firmly ligated just above the cisterna chyli. The immediate postoperative course was uneventful, oral feeding was started on postoperative day 8, and the patient was discharged home 5 days later. Three weeks after discharge, he was readmitted to the hospital for progressive respiratory insufficiency characterized by shortness of breath and dyspnea. Standard chest radiograph showed an extensive left pleural effusion that justified transthoracic needle aspiration. Thirteen hundred milliliters of lipid- and lymphocyte-rich milky fluid was aspirated with subsequent symptomatic relief and discharge. However, routine chest radiographs performed a few days later showed recurrence of the left pleural effusion, which testified to the existence of a chronic lymphatic weeping, probably originating from accessory lymphatic pathways in the posterior mediastinum.6 After transthoracic needle aspiration of the recurrent effusion, somatostatin-14 was administered by continuous IV infusion at 6 mg/d, while the patient was maintained in the fasting state and given TPN. Somatostatin therapy was maintained for a 14-day period, after which oral feeding was started again without subsequent recurrence of the pleural effusion. No adverse effect of the drug was observed during or after treatment. Six months after the initial operation, the patient takes a normal diet without experiencing any dysphagia, and the standard chest radiograph is unremarkable.


   Discussion
TOP
 Abstract
 Report of Cases
 Discussion
References
 
Leak of lymphatic fluid is a rare but embarrassing complication of thoracic or cervical surgery. It is indeed difficult to treat, and it results most of the time in an expensive, prolonged in-hospital stay. Moreover, we know from continuous drainage of the thoracic duct in organ transplantation10 that prolonged loss of proteins and lymphocytes alters immunologic defense mechanisms, a condition that may predispose critically ill patients to systemic infection.

Various therapeutic methods have been used against such lymphatic fluid weepings. Since the first ligation of the thoracic duct at the cervical level by Cushing11 > 100 years ago and at the thoracic level by Lampson12 50 years later, the classic method consists of repeat thoracotomy for ligation of the lymphatic vessel together with all fatty and fibrous tissues lying between the right azygous vein and the aorta just above the diaphragm.13 14 More recently, right thoracoscopy4 has been shown to be an elegant technical modality for approaching the thoracic duct, allowing division of the vessel between metal clips under videoscopic control. A few years ago, Japanese surgeons reported successful management of a thoracic duct injury after pneumonectomy by application of fibrin glue on the site of laceration through the working channel of a bronchofiberscope that had been inserted into the pleural cavity through a 28F chest tube.15 Talc-induced pleurodesis is an alternative to repeat thoracotomy.16 Likewise, leakage from the cervical segment of the thoracic duct has successfully been treated by local injection of tetracycline hydrochloride.17 In another report, mediastinal radiotherapy has been shown to be effective in resolving chylothorax secondary to neoplastic obstruction of the superior vena cava and thoracic duct.18 Recently, IV administration of an {alpha}-adrenergic drug such as etilefrin hydrochloride has been shown to be capable of drying up intra-abdominal lymphatic weeping after resection of the esophagus en bloc with the thoracic duct.19

Case 1 of the current article confirms data from other authors1 2 3 that the administration of somatostatin-14 may be very effective against thoracic surgery-related lymphatic leaks that do not respond to TPN alone. Within a few days indeed, lymphatic fluid outflow reduced dramatically, and no rebound effect was observed while the dose of the drug was reduced progressively until complete discontinuation. In case 2, the role of somatostatin-14 in drying up lymphatic leakage was less unequivocal than in case 1, inasmuch as TPN, which was started as the same time as somatostatin-14 therapy was initiated, might have contributed to reducing lymphatic fluid outflow.

Little is known about the mechanism of action of somatostatin regarding chyle production on the one hand and intraluminal pressure in the lymphatic system on the other. Although somatostatin reduces intestinal absorption of fats20 21 as well as triglyceride concentrations in thoracic duct lymph,22 the question of whether the drug acts on nutrient absorption by direct interference with the transport process in the gut wall, or indirectly by lowering intestinal blood flow23 or motility,24 remains unanswered to date. Nakabayashi and coworkers22 have shown in animal studies that somatostatin infusion through either the portal or the femoral vein exerts an attenuating effect on thoracic duct lymph flow, probably in relation to changes in the splanchnic lymph dynamics. The same authors also showed that the attenuating effect was abolished by truncal vagotomy. However, the fact that our second patient had had truncal vagotomy contradicts the second observation of this group.

In any case, although further pathophysiologic studies are needed for the elucidation of the mechanism of action of the drug, somatostatin-14 infusion appears to be an intriguing alternative method for drying up postsurgical lymphatic leaks. Because of the poor general condition of most of the patients concerned, this medical treatment should be attempted before reopening of the chest for lymphostasis and, in any case, in the presence of residual lymphatic weeping after primary ligation of the thoracic duct. However, because somatostatin modulates the blood glucose regulatory system,25 26 we recommend monitoring of blood glucose every 6 h during treatment. In addition, the standard doseage of 6 mg/d must be reduced to 3 mg/d during at least a 48-h period to prevent any rebound effect.


   Footnotes
 
Abbreviation: TPN = total parenteral nutrition

Received for publication March 23, 1999. Accepted for publication September 7, 1999.


   References
TOP
 Abstract
 Report of Cases
 Discussion
 References
 

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  5. Riquet, M, Hidden, G, Debesse, B (1989) Les collatérales du canal thoracique d’origine ganglio-pulmonaire. Etude anatomique et chylothorax après chirurgie pulmonaire. Ann Chir 43,646-457[ISI][Medline]
  6. Lachapele, AP, Hugues, A, Lagarde, C (1964) De l’étude anatomo-radiologique du canal thoracique d’après 60 opacifications sur l’être humain vivant. J Radiol Electrol 45,1-10
  7. Collard, JM, Romagnoli, R, Hermans, BP, et al (1997) Results of radical esophageal resection for adenocarcinoma arising in Barrett’s esophagus. Am J Surg 174,307-311[CrossRef][ISI][Medline]
  8. Collard, JM, Tinton, N, Malaise, J, et al (1995) Esophageal replacement: gastric tube or whole stomach? Ann Thorac Surg 60,261-267[Abstract/Free Full Text]
  9. Collard, JM, Otte, JB, Reynaert, M, et al (1995) Extensive lymph node clearance for cancer of the esophagus or cardia: merits and limits in reference to 5-year absolute survival. Hepatogastroenterology 42,619-627[Medline]
  10. Starzl, TE, Weil, R, Koep, LJ, et al (1979) Thoracic duct drainage before and after cadaveric kidney transplantation. Surg Gynecol Obstet 149,815-821[ISI][Medline]
  11. Cushing, H (1898) Operative wounds of the thoracic duct: report of a case with suture of the duct. Ann Surg 27,719-728[Medline]
  12. Lampson, RS (1948) Traumatic chylothorax. J Thorac Surg 17,778-791[Medline]
  13. Milson, JW, Kron, IL, Rheuban, KS, et al (1985) Chylothorax: an assessment of current surgical management. J Thorac Cardiovasc Surg 89,221-227[Abstract]
  14. Simpson, L (1988) Chylothorax. Jamieson, GG eds. Surgery of the esophagus ,873-876 Churchill Livingstone Edinburgh, UK.
  15. Shirai, T, Amano, J, Takabe, K (1991) Thoracoscopic diagnosis and treatment of chylothorax after pneumonectomy. Ann Thorac Surg 52,306-307[Abstract]
  16. Adler, RH, Levinsky, L (1978) Persistent chylothorax. J Thorac Cardiovasc Surg 76,859-864[Abstract]
  17. Metson, R, Alessi, D, Calcaterra, TC (1986) Tetracycline sclerotherapy for chylous fistula following neck dissection. Arch Otolaryngol Head Neck Surg 112,651-653
  18. Heaton, RW, Arnold, IR, Howard, N, et al (1987) Successful treatment of chylothorax and superior vena cava obstruction by radiotherapy. Thorax 42,153-154[ISI][Medline]
  19. Collard, JM, Laterre, PF, Reynaert, M, et al (1992) Unusual but severe complications following en-bloc resection of the oesophagus for cancer. Gullet 2,129-231
  20. Marki, F (1981) Effect of somatostatin on intestinal absorption of nutrients in the rat. Regul Pept 2,371-381[CrossRef][ISI][Medline]
  21. Hengl, G, Prager, J, Pointner, H (1979) The influence of somatostatin on the absorption of triglycerides in partially gastrectomized subjects. Acta Hepato-Gastroenterol 26,392-395
  22. Nakabayashi, H, Sagara, H, Usukura, N, et al (1981) Effect of somatostatin on the flow rate and triglyceride levels of thoracic duct lymph in normal and vagotomized dogs. Diabetes 30,440-445[ISI][Medline]
  23. Wahren, J, Felig, P (1976) Influence of somatostatin on carbohydrate disposal and absorption in diabetes mellitus. Lancet 2,1213-1216[ISI][Medline]
  24. Cohen, ML, Wiley, KS, Yaden, E, et al (1979) In vitro actions of somatostatin, D-Val1, D-Trp8-somatostatin and glucagon in rabbit jejunum and guinea-pig ileum. J Pharmacol Exp Ther 211,423-429[Free Full Text]
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