Visceral fistula as a complication of endoscopic treatment of esophageal and gastric varices using isobutyl-2-cyanoacrylate: Report of two cases

Visceral fistula, complication of sclerotherapy using isobutyl-2-cyanoacrylate

Visceral fistula as a complication of endoscopic treatment of esophageal and gastric varices using isobutyl-2-cyanoacrylate: report of two cases Giorgio Battaglia, MD, Tiziana Morbin, MD, Elisabetta Patarnello, MD, Carlo Merkel, MD, Matteo Chiesura Corona, MD, Ermanno Ancona, MD

G Battaglia, T Morbin, E Patarnello, et al.

rience, major non-hemorrhagic complications after the use of bucrylate were rare and, apart from the visceral fistulae in the two cases described in this report, these included four cases of pulmonary microembolism and one of pelvic microembolism, all of which were asymptomatic.9 CASE REPORTS Case 1

Endoscopic treatment of gastric varices by injection of bucrylate was first proposed by Soehendra et al.1 in 1986. Published results of this method of therapy have usually been excellent,2-6 especially when it is used for emergency treatment. Although not widely accepted, we generally dilute isobutyl-2cyanoacrylate (1:1) with lipiodol (an oily contrast medium). The intravariceal injection of a tissue glue has potential complications. Bucrylate-specific complications reported include pulmonary microembolism and cerebral embolism as described by See et al.7 in two patients. Fabiani et al.8 have also described autopsy findings in three patients who died as a consequence of undiagnosed mediastinitis. In our expeFrom the 4th Department of Surgery, 5th Department of Medicine, and Department of Radiology, University of Padua, Padua, Italy. Reprint requests: Giorgio Battaglia, MD, 4th Dept. of Surgery, University of Padua, Via Giustiniani 2, Padova, 35128 Italia. Copyright © 2000 by the American Society for Gastrointestinal Endoscopy 0016-5107/2000/$12.00 + 0 37/4/105080 doi:10.1067/mge.2000.105080 VOLUME 52, NO. 2, 2000

A 65-year-old woman with liver cirrhosis of mixed etiology (alcoholic and viral) presented with upper GI hemorrhage, manifested by hematemesis and melena, that had begun 48 hours earlier. Six years earlier she had undergone sclerotherapy for esophageal varices with 1.5% polidocanol at our hospital and eradication had been achieved. Her liver function status was Child C. On admission, the patient underwent upper endoscopy which showed eradication of esophageal varices and an F3 gastric varix extending toward the lesser curvature with a fibrin plug (NEC classification of gastric varices).9,10 A total of 6 mL of bucrylate-lipiodol (1:1) was therefore injection and hemostasis was achieved. The clinical course was complicated by recurrent hemorrhage from the gastric fundal varices, and another session of injection treatment with bucrylate proved to be necessary. After 6 months of follow-up, a thoracoabdominal CT was performed. CT of the chest and abdomen was initially included in our post-treatment protocol to look for evidence of pulmonary or pelvic micro-embolism. Because this complication occurred in only 5 of our patients, we now use conventional x-ray of the chest and abdomen. CT revealed hyperdense areas in the fundus of the stomach corresponding to the location of the short gastric vessels GASTROINTESTINAL ENDOSCOPY

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Visceral fistula, complication of sclerotherapy using isobutyl-2-cyanoacrylate

Figure 1. Gross appearance of spleen. that were a result of the previous treatment. There was splenomegaly with parenchymal features compatible with an intra-parenchymal subcapsular hematoma of the spleen. In the days that followed, abdominal US showed distortion of the subcapsular features and, because we suspected a rupture of the spleen, the patient underwent splenectomy. During surgery it was impossible to explore the abdominal cavity because the gastric fundus was closely attached to the diaphragm and was hypervascular. This was interpreted, also on the strength of the CT findings, as the result of a perivisceritis due to injection treatment performed 6 months earlier, and it was thought best to avoid further surgical exploration as this would entail considerable risk. Macroscopically, there were large yellowish areas on the surface of the spleen that we initially interpreted as cancerous lesions (Fig. 1). However, histopathologic evaluation demonstrated that these were necrotic areas due to ischemic events with numerous arteries that already exhibited organized thrombi. Postoperatively, the patient’s respiration became impaired and a left pleural empyema was diagnosed (Fig. 2). A thoracic drainage tube was inserted and treatment with antibiotics was initiated. The pulmonary findings persisted with periods of recrudescence. An x-ray film with the injection of a contrast medium through the chest drain revealed a fistula between the gastric cavity and the pleural cavity. To verify this diagnosis, methylene blue was injected through the drainage tube and was seen to pour out of a tiny hole in the gastric fundus (Fig. 3). A nasogastric tube was positioned in the stomach for aspiration and then the thoracic drainage tube was used for lavage of the empyematous cavities and for aspiration. Complete healing of the fistula was thus achieved within 3 weeks. Case 2 A 68-year-old man with hepatocellular carcinoma and hepatitis C–related liver cirrhosis presented with a major relation of upper GI hemorrhagic that was controlled by balloon tamponade. Comorbid conditions included insulindependent diabetes mellitus and severe ischemic cardiomyopathy. His liver function status was Child C. Endoscopy revealed blue, F3 varices with active bleeding. Sclerotherapy was attempted using a total of 24 mL of 1.5% polido268

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Figure 2. CT of chest showing empyema involving the left pleura. canol injected both intravariceally and perivariceally; this failed to stop the hemorrhage. Intravariceal injection of cyanoacrylate was therefore performed and this achieved hemostasis. Follow-up endoscopy 7 days later showed distension of the varices and an area of necrosis about 1 cm in diameter (Fig. 4). The presence of this area of necrosis aroused a suspicion that there might be an esophageal fistula, although this was not apparent from contrast x-ray films of the digestive tract made with a water-soluble medium. The patient underwent conservative treatment (nasogastric tube aspiration, total parenteral nutrition). A followup endoscopy performed on day 14 showed a deeper necrotic area and severe sloughing of the mucosa (Fig. 5). Contrast esophagography was not performed because of the onset of a severe attack of angina. Despite the lack of clinical findings, conservative treatment measures were continued for 7 days and then the patient resumed oral feeding. Endoscopy 1 month later disclosed the presence of a profound esophageal eschar; contrast esophagography with a water-soluble medium confirmed the suspicion at endoscopy of fistula and chest x-ray showed right paramediastinal exudate (Fig. 6). A trans-fistular probe was consequently inserted under fluoroscopic guidance for the dual purpose of lavage with an antibiotic solution and drainage of the exudate. Endoscopy on day 45 showed a reduction in the fistula, but a CT of the chest confirmed the paramediastinal opacity. A thoracic drainage tube was therefore inserted. A few days later, the patient suffered a severe episode of hemoptysis associated with severe respiratory deficiency. The patient underwent surgery 50 days after the initial endoscopic treatment session. A right thoracotomy was performed which revealing extensive excavation and destruction of the pulmonary parenchyma and exposure of the pulmonary vessels. The right lower lobe was decorticated, the breaches in the airways were sutured, and VOLUME 52, NO. 2, 2000

Visceral fistula, complication of sclerotherapy using isobutyl-2-cyanoacrylate

Figure 3. Endoscopic view of the fundus of the stomach showing methylene blue dye that had been injected via a drain in the thorax.

G Battaglia, T Morbin, E Patarnello, et al.

Figure 5. Endoscopic view of the esophagus showing sloughing of the mucosa.

Figure 4. Endoscopic view of the esophagus showing area of necrosis with suspected fistula. drainage tubes were positioned in areas where there was an accumulation of pus. The patient died 6 days after surgery (56 days after the initial endoscopic treatment) due to multiple organ failure. Autopsy revealed pulmonary abscesses, a completely re-epithelized esophageal mucosa, but total destruction of the muscle layer of the esophagus.

DISCUSSION These two cases differed in their evolution and especially their final outcome, but they had in common the complication of a fistula due to endoscopic injection treatment with bucrylate. The slow progression in the first case allowed for a different, more balanced therapeutic approach compared with the second case where there was a rapid clinical course. An analysis of these two cases leads to the following conclusions: First, bucrylate produces major VOLUME 52, NO. 2, 2000

Figure 6. Lateral chest x-ray showing fistula and paramediastinal collection.

inflammatory reactions that can involve all layers of the esophageal wall and the arterial vessels. In the first case, there was no evidence of bucrylate embolism in the spleen; this could mean either that the resin had occluded some branches of the splenic vascularization or that it had embolized intraGASTROINTESTINAL ENDOSCOPY

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parenchymal vessels and had then been eliminated by macrophage action. Second, in the event of a complication, it is essential to provide complete and immediate treatment, even if only conservative. In case 2, our basic mistake was to underestimate the severity of the complication, which led to treatment with inadequate drainage, thus allowing the infectious process to damage the pulmonary parenchyma and vessels. Another observation concerns the macroscopic lesions usually found after injection of tissue glue: once the plug has fallen away, the esophageal wall appears severely damaged, revealing profound ulcers, but there is usually a rapid process of re-epithelization and healing occurs quickly. Even at autopsy there was complete closure of the fistula despite widespread destruction of the surrounding tissue. Although traditional methods of sclerotherapy have been thoroughly studied and their possible complications are well known,11,12 the use of cyanoacrylate for treating esophageal or gastric varices has yet to become routine. Severe complications have been described and, as in our cases, these may become evident several weeks after implementing the treatment. Close follow-up of the locus of injection is consequently of fundamental importance. We now use endoluminal US and careful baseline clinical evaluation so that the occurrence of a complication can be detected immediately. REFERENCES 1. Soehendra N, Nam VC, Grimm H, Kempeneers I. Endoscopic obliteration of large esophagogastric varices with bucrylate. Endoscopy 1986;18:25-6.

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2. Ramond MJ, Valla D, Mosnier JF, Degott C, Bernuau J, Rueff B, et al. Successful endoscopic obliteration of gastric varices with butyl-cyanoacrylate. Hepatology 1989;10:488-93. 3. D’Imperio N, Piemontese A, Baroncini D, Billi P, Borioni D, Dal Monte PP, et al. Evaluation of undiluted N-butyl-2-cyanoacrylate in the endoscopic treatment of upper gastrointestinal tract varices. Endoscopy 1996;28:239-43. 4. Ramond MJ, Valla D, Gotlib JP, Rueff B, Benhamou JP. Obturation endoscopique des varices oesogastriques par le Bucrylate. Etude clinique de 49 malades. Gastroenterol Clin Biol 1986;10:575-9. 5. Ramond MJ. Tecniques et indications du traitement endoscopique des varices oeso-gastriques en 1995. Gastroenterol Clin Biol 1995;19:921-34. 6. Soehendra N, Grimm H, Nam VC, Berger B. N-butyl-2-cyanoacrylate: a supplement to endoscopic sclerotherapy. Endoscopy 1987;19:221-4. 7. See A, Florent C, Lamy P, Levy VG, Bouvry M. Cerebrovascular accidents after endoscopic obturation of esophageal varices with isobutyl-2-cyanoacrylate in 2 patients [in French]. Gastroenterol Clin Biol 1986;10:604-7. 8. Fabiani B, Degott C, Ramond MJ, Valla D, Beniamou JP, Potet F. Obturation endoscopique des varices oeso-gastriques par le Bucrylate. Etude morphologique a partir de 12 cas autopsies. Gastroenterol Clin Biol 1986;10:580-3. 9. Battaglia G, Morbin T, Patarnello E, Carta A, Coppa F, Ancona A. Diagnostic et traitement endoscopique des varices gastrique. Acta Endoscopica 1999;29:116-7. 10. Battaglia G, Gerunda GE. NIEC classificatione of gastric varices. In: Spina GP, Arcidiacono R, editors. Gastric endoscopic features in portal hypertension. Milan: Masson; 1994. p. 69-72. 11. Ng EKW, Chung SCS, Leong HT, Li AKC. Perforation after endoscopic injection sclerotherapy for bleeding gastric varices. Surg Endosc 1994;8:1221-2. 12. Södelund C, Wiechel KL. Oesophageal perforation after sclerotherapy for variceal haemorrage. Acta Chir Scand 1983; 149:491-5.

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