Topical Mitomycin C 2017

Topical Mitomycin C Application in Pediatric Patients with Recurrent Esophageal Strictures-Report on Unfavorable Results.

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Abstract

OBJECTIVE:

Recurrent esophageal strictures (ESs) following esophageal atresia repair or caustic ingestion represent a common clinical problem. Recently, Mitomycin C was reported to improve the outcome of patients by reducing the number of endoscopic dilatations. However, other groups failed to exhibit a beneficial effect. We report on our experience with topic Mitomycin C application following endoscopic dilatation for recurrent ES.

METHODS:

Retrospective chart review of patients with ES treated at the Hannover Medical School (Location A) and the University of Leipzig (Location B) between 2009 and 2015. A Mitomycin C-soaked cotton swab was endoscopically placed at the area of stricture in all subjects. Successful treatment was defined as resolution of stricture after Mitomycin C therapy with not more than three dilatations thereafter. Our results were compared with published outcomes of alternative studies that involved 10 or more patients.

RESULTS:

A total of 11 children received Mitomycin C concurrently with endoscopic dilatations. Seven children (64%) had gross type C esophageal atresia, two patients (18%) gross type A esophageal atresia, and two children (18%) caustic injury.After a median follow-up of 34 months (range, 14-75 months) and a median number of 3 ± 2.5 dilatations with Mitomycin C application per patient (range, 1-9), 6 of 11 patients (55%) achieved a resolution of their structures. Five patients (45%) did not respond to Mitomycin C therapy, of which two needed esophageal redo-surgery.

CONCLUSION:

We failed to confirm the high success rates of Mitomycin C treatment for recurrent ESs. Given the fact that there is limited data to prove the beneficial effect of Mitomycin C treatment, pediatric surgeons should carefully consider whether the advantages of this therapy outweigh the necessity of life-long endoscopic follow-ups. Further randomized controlled studies are recommended.

https://www.ncbi.nlm.nih.gov/pubmed/29270948

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Use of Mitomycin C for Refractory Esophageal Stricture following Tracheoesophageal Fistula Repair

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Esophageal stricture is a well-described complication following tracheoesophageal fistula repair. Herein, we report two patients who had persistent esophageal strictures after several months of repeat balloon dilatations. Each patient was treated with a single application of topical mitomycin C in addition to esophageal dilatation, which resulted in complete resolution of the stricture.

Introduction

Tracheoesophageal fistulas (TEFs) are treated with operative ligation of the distal fistula and anastomosis of the esophageal limbs. The development of an esophageal stricture at the anastomosis is a well-described complication after repair, occurring in approximately one-third of patients.1 Endoscopic balloon dilatation is currently the preferred method of treatment for both initial and recurrent esophageal strictures. Recently, the use of topical mitomycin C (MMC) for the treatment of esophageal strictures after surgical repair and caustic injury has been reported. In these studies, MMC treatment was largely successful in the resolution of esophageal strictures with a minimal complication profile. However, the vast majority of the reported cases of MMC use in esophageal strictures have been secondary to caustic injury, with a paucity of reported cases after newborn TEF repair. Herein, we report the successful use of topical MMC in combination with balloon dilatation for the treatment of refractory esophageal strictures following TEF repair in two neonates with complete resolution of the stricture without complications.

Case 1

A 39-week infant girl, born with VACTERL syndrome, was initially diagnosed with a long-gap pure esophageal atresia due to inability to pass a nasogastric tube and a gasless abdomen on abdominal radiograph. Shortly after birth, the patient underwent a gastrostomy tube placement and end colostomy for imperforate anus. Two months later, she underwent a right-sided thoracotomy, where a Type C TEF was encountered, as opposed to a pure esophageal atresia. She underwent ligation of the distal fistula, resection of a nonpatent fibrous cord of the distal esophageal limb with subsequent anastomosis of the esophageal limbs under tension. A postoperative esophagram revealed an anastomotic leak, which eventually resolved. Four months postoperatively, she underwent a follow-up esophagram which revealed a tight stricture at the anastomosis. She underwent endoscopic balloon dilatation with fluoroscopic guidance every month for four consecutive months with persistence of the stricture at the anastomosis and no improvement.

Case 2

A 31-week twin infant girl underwent repair of a Type C TEF. Before thoracotomy, the patient’s clinical condition deteriorated with marked distention of her abdomen. An open gastrostomy was first performed and placed to water seal, and a thoracotomy with ligation of a distal TEF and esophagoesophagostomy was performed under moderate tension. One month later, she developed symptoms of feeding intolerance, reflux, and tracheal aspiration. A repeat esophagram demonstrated a near-obstructing stricture in the midesophagus. The stricture was short, circumferential, and located at the site of the anastomosis. She was taken to the operating room for endoscopic balloon dilatation with fluoroscopic guidance, and subsequently underwent three more monthly balloon dilatations; however, there was no interval improvement in the stricture.

At 5 months of age, MMC was applied during the fifth esophageal dilatation in the same manner as described above. The patient underwent a follow-up surveillance endoscopy, which demonstrated no evidence of residual stricture. Two and a half years after the sole MMC application and dilatation, she remains asymptomatic.

Discussion

Esophageal stricture after TEF repair can develop when anastomoses are performed under the vascular compromise or when esophageal limbs are joined under tension. Recurrent strictures may occur in patients with a predisposition for intense fibrinogenesis during anastomotic healing or as a wound healing response after esophageal dilatation treatment. Based on this model, MMC may be an ideal treatment to break the cycle of fibrosis and recurrent stricture formation.

MMC is an antineoplastic agent isolated from Streptomyces caespitosus, which can reduce scar formation by suppression of fibroblast proliferation and fibroblastic collagen synthesis via inhibition of DNA-dependent RNA synthesis. The anti-fibroblast properties of MMC have been applied to limit scar formation. A review of 31 pediatric patients with refractory esophageal strictures due to a variety of etiologies treated with MMC reports an 87.7% rate of improvement in symptoms.

With regards to MMC use for esophageal strictures, there have been only five previously reported cases following surgical repair in the neonatal period for variants of TEF with esophageal atresia: three after Type C TEF repair and two after pure esophageal atresia repair. Of these reported cases, the authors attributed the refractory esophageal stricture to concomitant reflux in three cases and to a repair performed under tension in one case. In four of the five cases reported, three to eight esophageal dilatations were performed before the application of MMC. All had successful resolution of the strictures without procedural complications. Similarly, our patients likely formed strictures due to repair performed under tension. We recommend the prompt addition of MMC after a moderate amount of dilatations with the rationale to break the proposed cycle of fibrinogenesis and refractory stricture formation.

Initial reports of the use of MMC demonstrate a good safety profile. However, one study of six pediatric patients with refractory esophageal stenosis discovered evidence of de novo gastric metaplasia on follow-up esophageal biopsy in two patients. Furthermore, MMC can be absorbed mucosally causing systemic side effects, which include bone marrow suppression and hypersensitivity reactions. The majority of the literature describes the procedure as being safe without adverse effects.

Conclusion

This case report supports the utility and safety of MMC treatment as an adjunct to endoscopic balloon dilatation in managing refractory esophageal strictures following TEF repair. Despite multiple failed esophageal dilatation attempts, our two patients have remained asymptomatic and stricture-free over 2 years after a single application of MMC, potentially saving these children from additional procedures.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335951/

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