Endoscopic Treatment of Bronchopleural Fistulas

Endoscopic Treatment of Bronchopleural Fistulas Federico Varoli, MD, Giancarlo Roviaro, MD, Fabrizio Grignani, MD, Contardo Vergani, MD, Marco Maciocco, MD, and Carlo Rebuffat, MD Department of Surgery, University of Milan, San Giuseppe Hospital, Milan, Italy

Background. Bronchial fistula is one of the most serious complications of pulmonary resection. Methods. We present an endoscopic treatment that consists of multiple submucosal injections of polidocanol– hydroxypoliethoxidodecane (Aethoxysklerol Kreussler) on the margins of the fistula using an endoscopic needle inserted through a flexible bronchoscope. Results. From 1984 to 1995, 35 consecutive nonselected patients with a postresectional bronchopleural fistula were treated. All 23 partial postpneumonectomy or postlobectomy bronchopleural fistulas, ranging from 2 to

10 mm in diameter, healed completely. This did not occur in the 12 total bronchial dehiscences. No complications occurred due to the injection of the drug. Conclusions. In our opinion this treatment can be considered a valid therapeutic approach, as it is simple, safe, scarcely traumatic, and inexpensive, particularly considering that, in patients in stable condition, it can be performed as an outpatient treatment.

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sklerol Kreussler). All patients received thorough information on the procedure and provided their informed consent. There were 19 postpneumonectomy and 16 postlobectomy fistulas. The bronchial stump had been closed with mechanical suture in 19 patients, with Vicryl (Ethicon, Somerville, NJ) in 14, with Dexon (Davis & Geck, Wayne, NJ) in 1, and with silk in one of the very first patients. The operations had been performed for inflammatory lesions in 7 patients (2 pneumonectomies and 5 lobectomies) and for cancer in 28. The fistulas developed from 3 days to 25 years after operation. The fistulas were divided according to the modified classification of Le Brigand [12] into “early” (fistula occurring 1 to 7 days after the operation), “intermediate” (8 to 30 days after the operation), and “late fistula” (more than 30 days after the operation). According to the cited classification, we treated 1 early, 20 intermediate, and 14 late fistulas. The diameter of the fistulas ranged from 2 mm to total dehiscence of the bronchial stump. Fourteen patients had total dehiscence of the main or secondary bronchus, 7 had fistulas larger than 5 mm, and in the other 14 patients the diameter of the fistula was less than 5 mm. In 33 patients who also had an associated pleural empyema, a chest drain was positioned.

ronchial fistula is among the most dreaded and serious complications after pulmonary resection. Even after the introduction of bronchial staplers, it still occurs in 2% to 5% of all pulmonary resections, with a high mortality rate ranging between 18% and 50% [1–3]. The choice between surgical or conservative treatment of a bronchial fistula depends on the moment of appearance and on the clinical features [1, 2]. Today, many investigators attribute great importance to conservative bronchoscopic treatment [1]. The first experiences were accomplished by applying silver nitrate, but with uneven results [4]. In the past 10 years, fibrin and acrylic glues have been applied through flexible bronchoscopes, but again with uneven results [5– 8]. The evidence of granulation tissue in patients with esophageal varices submitted to endoscopic sclerosis with polidocanol (Aethoxysklerol Kreussler; Chemische Fabrik Kreussler & Co, GmbH, Wiesbaden, Germany) [9] prompted us to inject this drug within the bronchial submucosa on the edges of the fistula, in an attempt to stimulate the growth of granulation tissue and thereby seal the dehiscence [10]. This agent (polidocanol), mostly used for treating varicose veins, is also widely used for intravariceal or paravariceal injection to obtain sclerosis of esophageal varices [9, 11].

Material and Methods Patients From 1984 to 1995, we treated 35 consecutive nonselected patients with a postresectional bronchopleural fistula with endoscopic injections of polidocanol (AethoxyAccepted for publication Sep 11, 1997. Address reprint requests to Dr Varoli, Department of General Surgery, University of Milan, San Giuseppe Hospital FbF, Via San Vittore, 12, 20123 Milan, Italy.

© 1998 by The Society of Thoracic Surgeons Published by Elsevier Science Inc

(Ann Thorac Surg 1998;65:807–9) © 1998 by The Society of Thoracic Surgeons

Technique Endoscopic treatment consists of one or more sessions (carried out once every week) of multiple submucosal injections of polidocanol (Aethoxysklerol Kreussler) on the edges of the fistula. Under direct vision we advance an endoscopic needle through the bronchoscope’s operating channel and then administer several submucosal injections of 2% Aethoxysklerol Kreussler around the fistula. The amount of the drug used depends on the diameter of the fistula; we usually perform multiple injections until the ensuing swelling obtains the best 0003-4975/98/$19.00 PII S0003-4975(97)01427-6

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“mechanical” reduction of the lumen of the fistula. In almost all patients, no more than 4 to 5 mL of polidocanol is actually injected into the submucosa, but a larger dose is sometimes lost in the pleural cavity or aspirated by the bronchoscope. The injection generates a whitish reactive edema and a temporary reduction of the fistula. The edema regresses in 1 or 2 days when an intense inflammatory reaction takes over and the mucosa becomes hyperemic and remarkably thickened. After 6 to 7 days reactive tissue appears and proliferates from the edges toward the center of the fistula. The procedure may be repeated until a whitish fibrous tissue seals the fistula.

Results We did not observe any major complication during the treatment. Twenty-three of 35 patients (65.7%) recovered completely (11 postpneumonectomy and 12 postlobectomy fistulas). Operation had been undertaken in 4 patients for inflammatory disease (3 lobectomies and 1 pneumonectomy) and in 19 patients for lung cancer (10 pneumonectomies and 9 lobectomies). According to the modified Le Brigand classification [12], there were 1 early (postoperative day 6), 1 intermediate (postoperative day 14), and 21 late fistulas (range, 18 days to 25 years). The postpneumonectomy fistulas, which sealed completely, ranged between 2 and 10 mm, whereas the postlobectomy ones ranged from 2 to 6 mm. Healing time ranged from 2 to 8 weeks (mean, 5.5 weeks); only 1 patient recovered in 8 weeks but had chronic active hepatitis. After the bronchial stump had healed completely, we were able to obtain sterilization and complete recovery of the empyema. The remaining 12 patients had total dehiscence of a very short bronchial stump occurring after lobectomy (4 patients) or pneumonectomy (8 patients), and did not recover. Operation had been undertaken for tuberculosis (1 patient), for aspergilloma (1), for chronic empyema (1), and for cancer (9 patients). They were all intermediate and late fistulas (range, 14 to 92 days). After an apparent initial improvement, the granulation tissue did not develop. Five patients with postpneumonectomy fistulas died of cardiac or respiratory failure 1 to 2 weeks after the appearance of the fistula. In the remaining 7 patients, after an initial 50% reduction of the breach, treatment was discontinued after 6 to 8 weeks during which there were no signs of further improvement. Of these, in 1 patient with a postlobectomy fistula only a permanent chest drain was positioned due to poor general conditions; 6 underwent thoracoplasty (3 healed, 1 died of cardiorespiratory failure, and 2 were discharged with a permanent chest drain).

Comment Although the use of mechanical staplers has reduced the frequency of bronchial leakage, a fistula still remains a very serious complication of pulmonary resection [1–3]. The severity of clinical features and prognosis differ. After lobectomy, the expansion of the residual paren-

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chyma may minimize the consequences of the fistula. In contrast, in case of pneumonectomy, bronchial leakage always represents a very serious event with a high mortality rate, even up to 50% [3]. Among the several proposed classifications, Le Brigand [12] identifies fistulas according to the time of appearance after operation in early (1 to 4 days), intermediate (8 to 20 days), and late fistulas (more than 20 days). We have slightly modified his classification to include the periods of time not considered: early fistulas (1 to 7 days), intermediate fistulas (8 to 30 days), and late fistulas (more than 30 days). Early fistulas seem to be mainly related to technical errors, whereas intermediate and late fistulas seem mostly attributable to impaired healing of the bronchial stump. Aggressive treatment (assisted ventilation and surgical repair) is necessary in early bronchial fistulas when the clinical conditions are extremely severe due to unstable mediastinal structures [2, 12]. If the mediastinum is stable enough to allow sufficient spontaneous respiratory function, the first step is drainage so that conservative therapy may be carried out [2]. One early fistula (postoperative day 4) was also treated in this manner and healed within 4 weeks. In late and intermediate fistulas, because of the relative stability of mediastinal structures, many investigators now agree on conservative treatment as the first step [2, 3, 10]. Surgical approach (such as transternal mediastinal approach, thoracoplasty, omentopexy, intrathoracic muscle transposition) may be reserved for those patients with no tendency to healing. In our experience, 6 patients scarcely responsive to conservative treatment were submitted to thoracoplasty. Three patients healed, 1 patient died of respiratory failure, and the last 2 patients with persistent fistula died after 2 years. The surgical approach for intermediate and late fistulas after a conservative treatment has a success rate reported between 75% and 85% [13], but often it cannot be proposed to patients with poor general conditions and high operative risk. Conservative therapy requires drainage (as well as irrigation of the pleural cavity with antiseptic solutions if an empyema is present) and endoscopic treatment aimed at closing the bronchial fistula. Regarding the gluing materials, Glover and associates [7] reported 2 patients with bronchial leakage closed with fibrin glue; Torre and colleagues [6] reported 3 personal cases closed with acrylic glue, as well as 4 reported cases, 2 closed with acrylic glue and 2 with fibrin. In all patients the fistulas were successfully sealed [5, 14, 15]. Those researchers do not specify the total number of treated patients or the sizes of the fistulas. The largest reported diameter of a fistula healed with glue was 4.5 mm. To our knowledge, there are no reports of a total dehiscence treated with glue. A good success rate (83%) after application of methyl-2-cyanoacrylate has recently been reported, but only in very small postpneumonectomy fistulas (1 to 2 mm) or in postlobectomy fistulas less than 5.5 mm [16]. Torre and colleagues [17] has recently reported 16 patients treated with a 50% success rate, but healed fistulas were no more than 5 mm. According to the reports in literature, glues have the advantage of

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ensuring an immediate stop to the air leak, but involve remarkable technical difficulties because of the rapidity with which these materials solidify and the impossibility of applying this technique to all bronchi or to every kind of fistula. Furthermore, displacement of the glue plug causing obstruction of the bronchial tree with acute respiratory failure was repeatedly described [6]. The use of polidocanol submucosal injections affords no serious technical difficulties, and can be used on any bronchus, even the superior ones. We had no complications, such as tissue necrosis, that may rarely occur when an excessive dosage is injected into esophageal varicose veins. Furthermore, the occurrence of severe or fatal periesophagitis or mediastinitis (although described) is infrequent, and endoscopic sclerosis is thus considered a safe and convincing alternative for the treatment of esophageal varices. If we consider our field of application, the risk of complications seems even lower, as the injection is usually performed out of the mediastinum, on a bronchial stump generally already surrounded by conspicuous reactive inflammatory tissue. We obtained an average healing rate of 65% in all treated patients, which approaches the results of operation. Even more interesting is the 100% healing rate of partial fistulas as wide as 10 mm, or occurring after pneumonectomy. In our study the technique did not succeed in case of total dehiscence, but no other conservative technique proved useful in those cases either. In our opinion submucosal injection of polidocanol can easily be used in any bronchus, and gives better results than with the application of glue. Endoscopic gluing does not achieve such healing values, and healed fistulas are never larger than 5.5 mm originally. The 12 patients who did not recover had total dehiscence of the sutures applied close to the bronchial origin. In these patients the shortness of the bronchial stumps did not permit adequate submucosal injections around the fistula, and would probably also have precluded anchoring the glue plug. Submucosal injections of polidocanol have proved to be an easy, safe, relatively atraumatic, and very inexpensive method. Results were excellent and surpassed other techniques even with wide fistulas, whenever the bronchial stump was long enough to sustain the healing process. In contrast, total dehiscence of a suture close to the bronchial origin does not seem to permit sealing, but this also applies to other endoscopic treatments. We believe that the treatment of bronchopleural fistulas with bronchoscopic submucosal injections of polidocanol can be considered a valid therapeutic option in selected patients who do not have a total dehiscence of the bronchial stump. It may be advocated as the first thera-

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peutic step, especially as it does not preclude additional surgical procedures.

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