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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Esophageal Anastomotic Leak

Intervention / Treatment
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* Procedure: delay phenomenon by arteriographic approach


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: delay phenomenon by arteriography<br>intervention: delay phenomenon by arteriography. Patients who will be subjected a delay phenomenon by arteriographic procedure before esophageal resection surgery minimum 14 days before surgery. An angiogram of the celiac trunk is performed through a femoral access before and after the embolization. A 4-5 Fr Simmons or Cobra catheter is used for the catheterization and embolization of the left gastric artery, and 0.035-inch platinum coils are proximally placed from the main trunk in the splenic artery. When accessory left gastric arteries are present, they are catheterized and embolized as well. The right gastric artery catheterization is realized by a 4-5 Fr catheter and coils or microcoils are proximally placed in the artery as well. | Procedure: delay phenomenon by arteriographic approach<br>* we improve the microvascularization of the gastric fundus occluding the right and left gastric artery, and splenic artery two weeks before surgery by arteriography<br>|
| No Intervention: control group<br>Patients who will be operated directly without gastric ischemic conditioning. The investigators don't performed any arteriography before the esophageal surgical resection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| hospital stay | investigators will consider since the day of the surgery until the day the patient will be discharged from the hospital | 90 days | 
| major and minor morbidity | investigators will evaluate morbidity according to Clavien-Dindo classification | 90 days | 
| postoperative mortality |  | during hospitalization and/or 30 days after surgery | 
| 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 | 
| 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 |