Trial on Delay Phenomenon Utility in Preventing Anastomotic Leakage After an Esophagectomy

Esophageal Anastomotic Leak Clinical Trial

— APIL_2013  

Official title:

Prospective Randomized Clinical Trial on Delay Phenomenon Utility in Preventing Oesophagogastric Anastomotic Dehiscence After Ivor-Lewis Esophagectomy. Pilot Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02432794
• Other study ID #: APIL_2013
• Status: Completed
• Phase: N/A
• Start date: May 2015
• Est. completion date: June 2019

Study information

• Verified date: August 2019
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized clinical trial to clarify if the delay phenomenon could reduce the incidence of oesophagogastric dehiscence after an esophagectomy for esophageal cancer comparing an experimental group vs control group. The delay phenomenon will be performed by an arteriographic approach.

Description:

Subtotal esophagectomy with tubular gastroplasty to upper mediastinum and esophagogastric anastomosis (Ivor-Lewis procedure) is a very complex surgical technique. It is performed in patients with infracarinal esophageal carcinoma and is associated with a high morbidity rate in specialized centers (up to 60% in some groups). One of the most important postoperative complications is the oesophagogastric anastomotic leakage which leads to high morbidity (mediastinitis, respiratory failure, pleural effusion) and mortality rate (up to 60% depending on the reports).

The most important cause of anastomotic leakage is the stomach's extreme sensitivity to ischemic injury. There are several experimental studies that have demonstrated that the delay phenomenon before the esophageal resection surgery aims to improve blood perfusion after a period of time. Few studies, only case-reports, describe a decrease in the incidence of intrathoracic and cervical anastomotic leakage. May the delay phenomenon reduce the incidence of anastomotic intrathoracic leakage?. There aren't any prospective randomized controlled trials to answer this question.

For this reason the investigators propose to perform a prospective randomized controlled trial in patients who underwent a subtotal esophagectomy (Ivor-Lewis procedure), comparing two groups: one of them will be submitted to a delay phenomenon by arteriographic procedure before esophageal resection surgery, and the other one will be operated on directly, to demonstrate if the delay phenomenon can reduce the incidence of anastomotic esophagogastric leakage.

We decided to conduct this trial as a pilot study due to the fact that the number of patients needed to achieve statistical significance was to high and would have taken almost 10 years. We established a recruitment period of 3 years, in wich we intend to include 60 patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: June 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients requiring a subtotal esophagectomy with en-bloc resection and an intrathoracic esophagogastrostomy for esophageal cancer

• 18 or above years old

• Acceptance and signing the full informed consent

Exclusion Criteria:

• Absence of pancreatitis

• Anatomic vascular alteration that contraindicate the embolization (congenital celiac trunk stenosis, presence of arcuate ligament,etc,..)

• refuse to collaborate in the study

Related Conditions & MeSH terms

• Anastomotic Leak
• Esophageal Anastomotic Leak

Intervention

Procedure:
• delay phenomenon by arteriographic approach
we improve the microvascularization of the gastric fundus occluding the right and left gastric artery, and splenic artery two weeks before surgery by arteriography

Locations

Country	Name	City	State
Spain	Leandre Farran Teixidor	L'Hospitalet De Llobregat	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitari de Bellvitge

Country where clinical trial is conducted

Spain, 

References & Publications (15)

Akiyama S, Kodera Y, Sekiguchi H, Kasai Y, Kondo K, Ito K, Takagi H. Preoperative embolization therapy for esophageal operation. J Surg Oncol. 1998 Dec;69(4):219-23. — View Citation

Boyle NH, Pearce A, Hunter D, Owen WJ, Mason RC. Scanning laser Doppler flowmetry and intraluminal recirculating gas tonometry in the assessment of gastric and jejunal perfusion during oesophageal resection. Br J Surg. 1998 Oct;85(10):1407-11. — View Citation

Farran L, Miro M, Alba E, Bettonica C, Aranda H, Galan M, Rafecas A. Preoperative gastric conditioning in cervical gastroplasty. Dis Esophagus. 2011 May;24(4):205-10. doi: 10.1111/j.1442-2050.2010.01115.x. Epub 2010 Oct 11. — View Citation

Farran Teixidor L, Llop Talaverón J, Galán Guzmán M, Aranda Danso H, Miró Martín M, Bettónica Larrañaga C, Estremiana García F, Biondo S. [Surgical outcomes of esophageal cancer resection since the development of an Oesophagogastric Tumour Board]. Cir Esp — View Citation

González-González JJ, Sanz-Alvarez L, Marqués-Alvarez L, Navarrete-Guijosa F, Martínez-Rodríguez E. [Complications of surgical resection of esophageal cancer]. Cir Esp. 2006 Dec;80(6):349-60. Review. Spanish. — View Citation

Griffin SM, Shaw IH, Dresner SM. Early complications after Ivor Lewis subtotal esophagectomy with two-field lymphadenectomy: risk factors and management. J Am Coll Surg. 2002 Mar;194(3):285-97. — View Citation

Isomura T, Itoh S, Endo T, Akiyama S, Maruyama K, Ishiguchi T, Ishigaki T, Takagi H. Efficacy of gastric blood supply redistribution by transarterial embolization: preoperative procedure to prevent postoperative anastomotic leaks following esophagoplasty — View Citation

Lamas S, Azuara D, de Oca J, Sans M, Farran L, Alba E, Escalante E, Rafecas A. Time course of necrosis/apoptosis and neovascularization during experimental gastric conditioning. Dis Esophagus. 2008;21(4):370-6. doi: 10.1111/j.1442-2050.2007.00772.x. — View Citation

Liebermann-Meffert DM, Meier R, Siewert JR. Vascular anatomy of the gastric tube used for esophageal reconstruction. Ann Thorac Surg. 1992 Dec;54(6):1110-5. — View Citation

Metzger R, Bollschweiler E, Vallböhmer D, Maish M, DeMeester TR, Hölscher AH. High volume centers for esophagectomy: what is the number needed to achieve low postoperative mortality? Dis Esophagus. 2004;17(4):310-4. Review. — View Citation

Patil PK, Patel SG, Mistry RC, Deshpande RK, Desai PB. Cancer of the esophagus: esophagogastric anastomotic leak--a retrospective study of predisposing factors. J Surg Oncol. 1992 Mar;49(3):163-7. — View Citation

Schröder W, Beckurts KT, Stähler D, Stützer H, Fischer JH, Hölscher AH. Microcirculatory changes associated with gastric tube formation in the pig. Eur Surg Res. 2002 Nov-Dec;34(6):411-7. — View Citation

Schröder W, Hölscher AH, Bludau M, Vallböhmer D, Bollschweiler E, Gutschow C. Ivor-Lewis esophagectomy with and without laparoscopic conditioning of the gastric conduit. World J Surg. 2010 Apr;34(4):738-43. doi: 10.1007/s00268-010-0403-x. — View Citation

Urschel JD. Ischemic conditioning of the rat stomach: implications for esophageal replacement with stomach. J Cardiovasc Surg (Torino). 1995 Apr;36(2):191-3. — View Citation

Yuan Y, Duranceau A, Ferraro P, Martin J, Liberman M. Vascular conditioning of the stomach before esophageal reconstruction by gastric interposition. Dis Esophagus. 2012 Nov-Dec;25(8):740-9. doi: 10.1111/j.1442-2050.2011.01311.x. Epub 2012 Jan 31. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anastomotic leakage	investigators will consider anastomotic dehiscence the presence of one or more of the following conditions: radiologic confirmation by water-soluble contrast study (gastrografin administered orally) or thoracoabdominal Tc with oral contrast of dehiscence of oesophagogastric anastomosis or the stapler end of the gastroplasty.; When the clinical conditions of patient don't allow a Rx control investigators will consider an anastomotic leakage in these conditions: Thoracic drain output of oesophagogastric content with amylase > 40 ukAT/L, confirmation of anastomotic dehiscence by the surgeon during a reintervention, endoscopic confirmation of anastomotic leakage of the stapled end of the plasty and methylene blue output after oral administration (100 ml of water with 10ml of methylene blue)	7 days
Secondary	plasty ischemia	investigators will consider plasty ischemia when one or more of the following criteria is present: endoscopic evidence of gastric mucosa ischemia; evidence of low captation of the plasty in a thoracoabdominal CT with endovenous contrast that requires a reintervention.; intraoperative mortality (during hospitalization and/or 30 days after surgery).	7 days
Secondary	hospital stay	investigators will consider since the day of the surgery until the day the patient will be discharged from the hospital	90 days
Secondary	major and minor morbidity	investigators will evaluate morbidity according to Clavien-Dindo classification	90 days
Secondary	postoperative mortality		during hospitalization and/or 30 days after surgery
Secondary	post-embolization morbidity	investigators will consider post-embolization morbidity the following situations: abdominal pain with EVA>3 (evaluated by EVA classification ); pancreatitis diagnosed by abdominal pain and amylase > 5 uKat/L or by CT.; abscess, pseudocyst diagnosed by CT or during oesophageal surgery; spleen ischemia diagnosed by CT or abdominal ultrasound and needs some treatment; liver ischemia diagnosed by Ct or abdominal ultrasound; bleeding or artery dissection diagnosed during the embolization and needs some treatment; arterial pseudoaneurism diagnosed during the embolization or by CT	30 days
Secondary	anastomotic stricture	investigators will consider anastomotic stricture when they observe a reduction of anastomotic diameter by oral contrast Rx and needs some treatment (endoscopic dilation or reintervention)	6 months