Endoscopic vacuum therapy versus stent treatment of esophageal anastomotic leaks (ESOLEAK): study protocol for a prospective randomized phase 2 trial

Michael Tachezy, Seung-Hun Chon, Isabel Rieck, Marcus Kantowski, Hildegard Christ, Karl Karstens, Florian Gebauer, Tobias Goeser, Thomas Rösch, Jakob R Izbicki, Christiane J Bruns, Michael Tachezy, Seung-Hun Chon, Isabel Rieck, Marcus Kantowski, Hildegard Christ, Karl Karstens, Florian Gebauer, Tobias Goeser, Thomas Rösch, Jakob R Izbicki, Christiane J Bruns

Abstract

Background: Intrathoracic anastomotic leaks represent a major complication after Ivor Lewis esophagectomy. There are two promising endoscopic treatment strategies in the case of leaks: the placement of self-expanding metal stents (SEMS) or endoscopic vacuum therapy (EVT). Up to date, there is no prospective data concerning the optimal endoscopic treatment strategy. This is a protocol description for the ESOLEAK trial, which is a first small phase 2 randomized trial evaluating the quality of life after treatment of anastomotic leaks by either SEMS placement or EVT.

Methods: This phase 2 randomized trial will be conducted at two German tertiary medical centers and include a total of 40 patients within 2 years. Adult patients with histologically confirmed esophageal cancer, who have undergone Ivor Lewis esophagectomy and show an esophagogastric anastomotic leak on endoscopy or present with typical clinical signs linked to an anastomotic leak, will be included in our study taking into consideration the exclusion criteria. After endoscopic verification of the anastomotic leak, patients will be randomized in a 1:1 ratio into two treatment groups. The intervention group will receive EVT whereas the control group will be treated with SEMS. The primary endpoint of this study is the subjective quality of life assessed by the patient using a systematic and validated questionnaire (EORTC QLQ C30, EORTC QLQ-OES18 questionnaire). Important secondary endpoints are healing rate, period of hospitalization, treatment-related complications, and overall mortality.

Discussion: The latest meta-analysis comparing implantation of SEMS with EVT in the treatment of esophageal anastomotic leaks suggested a higher success rate for EVT. The ESOLEAK trial is the first study comparing both treatments in a prospective manner. The aim of the trial is to find suitable endpoints for the treatment of anastomotic leaks as well as to enable an adequate sample size calculation and evaluate the feasibility of future interventional trials. Due to the exploratory design of this pilot study, the sample size is too small to answer the question, whether EVT or SEMS implantation represents the superior treatment strategy.

Trial registration: ClinicalTrials.gov NCT03962244 . Registered on May 23, 2019. DRKS-ID DRKS00007941.

Keywords: Anastomotic leaks; Endoscopic vacuum therapy; Esophageal cancer; Esophagectomy; Interventional endoscopy; Self-expanding metal stents.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart illustrating the study design
Fig. 2
Fig. 2
Standardized documentation of diagnostic and therapeutic endoscopies
Fig. 3
Fig. 3
Timeline and important milestones of the study

References

    1. Low DE, Kuppusamy MK, Alderson D, Cecconello I, Chang AC, Darling G, Davies A, D’Journo XB, Gisbertz SS, Griffin SM, Hardwick R, Hoelscher A, Hofstetter W, Jobe B, Kitagawa Y, Law S, Mariette C, Maynard N, Morse CR, Nafteux P, Pera M, Pramesh CS, Puig S, Reynolds JV, Schroeder W, Smithers M, Wijnhoven BPL. Benchmarking complications associated with esophagectomy. Ann Surg. 2019;269(2):291–298. doi: 10.1097/SLA.0000000000002611.
    1. Rizk NP, Bach PB, Schrag D, Bains MS, Turnbull AD, Karpeh M, Brennan MF, Rusch VW. The impact of complications on outcomes after resection for esophageal and gastroesophageal junction carcinoma. J Am Coll Surg. 2004;198(1):42–50. doi: 10.1016/j.jamcollsurg.2003.08.007.
    1. Markar S, Gronnier C, Duhamel A, Mabrut JY, Bail JP, Carrere N, Lefevre JH, Brigand C, Vaillant JC, Adham M, Msika S, Demartines N, Nakadi IE, Meunier B, Collet D, Mariette C, FREGAT (French Eso-Gastric Tumors) working group, FRENCH (Fédération de Recherche EN CHirurgie), and AFC (Association Française de Chirurgie) The impact of severe anastomotic leak on long-term survival and cancer recurrence after surgical resection for esophageal malignancy. Ann Surg. 2015;262(6):972–980. doi: 10.1097/SLA.0000000000001011.
    1. Turkyilmaz A, Eroglu A, Aydin Y, Tekinbas C, Muharrem Erol M, Karaoglanoglu N. The management of esophagogastric anastomotic leak after esophagectomy for esophageal carcinoma. Dis Esophagus. 2009;22(2):119–126. doi: 10.1111/j.1442-2050.2008.00866.x.
    1. Low DE. Diagnosis and management of anastomotic leaks after esophagectomy. J Gastrointest Surg. 2011;15(8):1319–1322. doi: 10.1007/s11605-011-1511-0.
    1. Messmann H, et al. Endoscopic and surgical management of leakage and mediastinitis after esophageal surgery. Best Pract Res Clin Gastroenterol. 2004;18(5):809–827. doi: 10.1016/S1521-6918(04)00059-9.
    1. Lerut T, Coosemans W, Decker G, de Leyn P, Nafteux P, van Raemdonck D. Anastomotic complications after esophagectomy. Dig Surg. 2002;19(2):92–98. doi: 10.1159/000052018.
    1. Eroglu A, Turkyilmaz A, Aydin Y, Yekeler E, Karaoglanoglu N. Current management of esophageal perforation: 20 years experience. Dis Esophagus. 2009;22(4):374–380. doi: 10.1111/j.1442-2050.2008.00918.x.
    1. Grimminger PP, Goense L, Gockel I, Bergeat D, Bertheuil N, Chandramohan SM, Chen KN, Chon SH, Denis C, Goh KL, Gronnier C, Liu JF, Meunier B, Nafteux P, Pirchi ED, Schiesser M, Thieme R, Wu A, Wu PC, Buttar N, Chang AC. Diagnosis, assessment, and management of surgical complications following esophagectomy. Ann N Y Acad Sci. 2018;1434(1):254–273. doi: 10.1111/nyas.13920.
    1. Messager M, Warlaumont M, Renaud F, Marin H, Branche J, Piessen G, Mariette C. Recent improvements in the management of esophageal anastomotic leak after surgery for cancer. Eur J Surg Oncol. 2017;43(2):258–269. doi: 10.1016/j.ejso.2016.06.394.
    1. Dasari BVM, Neely D, Kennedy A, Spence G, Rice P, Mackle E, Epanomeritakis E. Role of esophageal stents in the management of esophageal anastomotic leaks and benign esophageal perforations. Ann Surg. 2014;259(5):852–860. doi: 10.1097/SLA.0000000000000564.
    1. Kuehn F, Loske G, Schiffmann L, Gock M, Klar E. Endoscopic vacuum therapy for various defects of the upper gastrointestinal tract. Surg Endosc Other Interv Tech. 2017;31(9):3449–3458. doi: 10.1007/s00464-016-5404-x.
    1. Virgilio E, Ceci D, Cavallini M. Surgical endoscopic vacuum-assisted closure therapy (EVAC) in treating anastomotic leakages after major resective surgery of esophageal and gastric cancer. Anticancer Res. 2018;38(10):5581–5587. doi: 10.21873/anticanres.12892.
    1. Plum PS, Herbold T, Berlth F, Christ H, Alakus H, Bludau M, Chang DH, Bruns CJ, Hölscher AH, Chon SH. Outcome of self-expanding metal stents in the treatment of anastomotic leaks after Ivor Lewis esophagectomy. World J Surg. 2019;43(3):862–869. doi: 10.1007/s00268-018-4832-2.
    1. Wedemeyer J, Schneider A, Manns MP, Jackobs S. Endoscopic vacuum-assisted closure of upper intestinal anastomotic leaks. Gastrointest Endosc. 2008;67(4):708–711. doi: 10.1016/j.gie.2007.10.064.
    1. Bludau M, Fuchs HF, Herbold T, Maus MKH, Alakus H, Popp F, Leers JM, Bruns CJ, Hölscher AH, Schröder W, Chon SH. Results of endoscopic vacuum-assisted closure device for treatment of upper GI leaks. Surg Endosc. 2018;32(4):1906–1914. doi: 10.1007/s00464-017-5883-4.
    1. Bludau M, Hölscher AH, Herbold T, Leers JM, Gutschow C, Fuchs H, Schröder W. Management of upper intestinal leaks using an endoscopic vacuum-assisted closure system (E-VAC) Surg Endosc. 2014;28(3):896–901. doi: 10.1007/s00464-013-3244-5.
    1. Berlth F, Bludau M, Plum PS, Herbold T, Christ H, Alakus H, Kleinert R, Bruns CJ, Hölscher AH, Chon SH. Self-expanding metal stents versus endoscopic vacuum therapy in anastomotic leak treatment after oncologic gastroesophageal surgery. J Gastrointest Surg. 2019;23(1):67–75. doi: 10.1007/s11605-018-4000-x.
    1. Dent B, Griffin SM, Jones R, Wahed S, Immanuel A, Hayes N. Management and outcomes of anastomotic leaks after oesophagectomy. Br J Surg. 2016;103(8):1033–1038. doi: 10.1002/bjs.10175.
    1. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg. 1997;38(6):563–576. doi: 10.1097/00000637-199706000-00002.
    1. Scognamiglio P, et al. Endoscopic vacuum therapy versus stenting for postoperative esophago-enteric anastomotic leakage: systematic review and meta-analysis. Endoscopy. 2020;52(8):632–642. doi: 10.1055/a-1149-1741.
    1. Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The comprehensive complication index: a novel continuous scale to measure surgicalmorbidity. Ann Surg. 2013;258(1):1–7. 10.1097/SLA.0b013e318296c732.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, Haes JCJM, Kaasa S, Klee M, Osoba D, Razavi D, Rofe PB, Schraub S, Sneeuw K, Sullivan M, Takeda F. The European Organization for Research and Treatment of Cancer QLQ-C30 - a Quality-Of-Life Instrument For Use In International Clinical-Trials In Oncology. J Natl Cancer Inst. 1993;85(5):365–376. doi: 10.1093/jnci/85.5.365.
    1. Blazeby JM, Conroy T, Hammerlid E, Fayers P, Sezer O, Koller M, Arraras J, Bottomley A, Vickery CW, Etienne PL, Alderson D, European Organisation for Research and Treatement of Cancer Gastrointestinal and Quality of Life Groups Clinical and psychometric validation of an EORTC questionnaire module, the EORTC QLQ-OES18, to assess quality of life in patients with oesophageal cancer. Eur J Cancer. 2003;39(10):1384–1394. doi: 10.1016/S0959-8049(03)00270-3.
    1. Schwarz R, Hinz A. Reference data for the quality of life questionnaire EORTC QLQ-C30 in the general German population. Eur J Cancer. 2001;37(11):1345–1351. doi: 10.1016/S0959-8049(00)00447-0.
    1. Vincent JL, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis- Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10. 10.1007/BF01709751.
    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–10. 10.1001/jama.2016.0287.

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