Laparoscopic Ischemic Conditioning Prior to Esophagectomy

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT03896399

Studienbeginn:
April 2019

Letztes Update:
12.01.2022

Wirkstoff:
-

Indikation (Clinical Trials):
Esophageal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
UMC Utrecht

Collaborator:
University Hospital of Cologne

Studienleiter

Richard van Hillegersberg, MD, PhD
Principal Investigator
University Medical Center Utrecht, dept. of Surgery

Wolfgang Schröder, MD, PhD
Principal Investigator
University Hospital of Cologne, department of Surgery

Kontakt

Eline De Groot, MD
Kontakt:
Phone: +316 49391569
E-Mail: e.m.degroot-26@umcutrecht.nl» Kontaktdaten anzeigen

Isabel Bartella, MD, PhD
Kontakt:
Phone: +492214784803
E-Mail: isabel.bartella@uk-koeln.de» Kontaktdaten anzeigen

Studienlocations
(2 von 2)

University Hospital of Cologne
50937 Cologne
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Isabel Bartella, MD, PhD
Phone: +49 (0)221-478 4803
E-Mail: isabel.bartella@uk-koeln.de

Wolfgang Schröder, MD, PhD
Phone: +49 (0)221-478 4803
E-Mail: wolfgang.schroeder@uni-koeln.de» Ansprechpartner anzeigen

University Medical Center Utrecht
3584 CX Utrecht
NetherlandsRekrutierend» Google-Maps
Ansprechpartner:
Arjen van der Veen, MD
Phone: +31 (0)88-755 8507
E-Mail: a.vanderveen-12@umcutrecht.nl

Richard van Hillegersberg, MD, PhD
Phone: +31 (0)88-755 8074
E-Mail: r.vanhillegersberg@umcutrecht.nl» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

Rationale:

Anastomotic leakage is the most important surgical complication following esophagectomy for

esophageal cancer, leading to increased morbidity and mortality. A major cause of leakage is

impaired healing due to ischemia of the gastric tube that is used for reconstruction of the

gastrointestinal tract. Calcifications of the aorta or stenosis of the celiac trunk on

pre-operative CT scan have been shown to be associated with an increased risk of anastomotic

leakage. So far, no individualized treatment has been initiated for this selected group of

patients. Laparoscopic ischemic conditioning (ISCON) of the gastric tube aims to increase

perfusion at the anastomotic site by redistribution of the gastric blood flow and/or

induction of angiogenesis. This is achieved by occlusion of the supplying gastric arteries

except for the right gastroepiploic artery during a separate intervention prior to

esophagectomy. Of note, these arteries would also be occluded during conventional

esophagectomy, but with laparoscopic ISCON they are occluded at an earlier moment in time

during a separate intervention. Retrospective studies have demonstrated the safety of this

technique. Prospective studies have not yet been performed.

Primary objective:

Assess the safety and feasibility of laparoscopic ISCON 12-18 days prior to esophagectomy for

esophageal cancer in patients with arterial calcifications.

Study design:

Two center phase II prospective single-arm safety and feasibility trial.

Study population:

Patients with resectable esophageal carcinoma (cT1-4a, N0-3, M0) with "major calcifications"

of the thoracic aorta (UCS) and any additional calcification or stenosis of the celiac axis

(modified NASCET score) on preoperative CT scan, who are planned to undergo esophagectomy.

Intervention:

Laparoscopic ISCON followed by esophagectomy after an interval of 12-18 days.

Primary outcome:

all complications grade 2 and higher (Clavien-Dindo classification) occurring during or after

operation 1 (laparoscopic ISCON) and before operation 2 (esophagectomy).

Secondary outcomes:

secondary outcomes with regard to operation 1 (laparoscopic ISCON) are the duration of the

procedure, blood loss, day of discharge postoperatively and grade 1 complications. Secondary

outcomes with regard to operation 2 (esophagectomy) are anastomotic leakage rate, all other

grade 3b or higher complications and 30 day mortality. Further secondary endpoints are the

induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow

by measurement of indocyanine green (ICG) fluorescence angiography.

Nature and extent of the burden and risks associated with participation, benefit and group

relatedness:

the additional burden for the patient consists of an extra operation of approximately 40

minutes during which laparoscopic ISCON will be performed, prior to the planned

esophagectomy. We would classify the current study as medium risk. Potential benefits in

comparison to current standard treatment are a reduced risk of anastomotic leakage and

severity of anastomotic leakage. Potential risks are complications following operation 1

(laparoscopic ISCON). Mainly, based upon prior experience, we expect gastroparesis to occur

in 25% of patients. Patients with gastroparesis have an increased risk of aspiration and will

require a stomach emptying by nasogastric tube and nasojejunal tube feeding till the

performance of operating 2 (esophagectomy).

Ein-/Ausschlusskriterien

Inclusion criteria:

- Histologically proven adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the

esophagus or gastroesophageal junction (GEJ)

- Planned to undergo transthoracic esophagectomy or transhiatal esophagectomy

- Preoperative computed tomography (CT)

- Vascular arterial changes: "major calcifications" of the thoracic aorta according to

the "Uniform calcification score" (UCS) and or a stenosis of the celiac axis according

to the "modified NASCET score". (Appendix 1 and 2) (7,17)

- ASA I-III

- European Clinical Oncology Group (ECOG) performance status of 0,1 or 2

- Age > 17

- Written informed consent

Exclusion criteria:

- Not able to undergo study treatment.

- Metastatic disease (M1)

Studien-Rationale

Primary outcome:

1. Number of participants with a grade 2 or higher complication after laparoscopic ischemic conditioning (Time Frame - Occuring after operation 1(laparosocpic ISCON), but before operation 2 (esophagectomy). This time-frame is usually 13-15 days.):
Complications grade 2 and higher (Clavien-Dindo classification)

Secondary outcome:

1. Number of participants with a grade 1 complication after operation 1 (laparoscopic ISCON) (Time Frame - Occuring after operation 1(laparosocpic ISCON), but before operation 2 (esophagectomy). This time-frame is usually 13-15 days.):
Grade 1 complications after operation 1 (laparoscopic ISCON)

2. Duration of operation 1 (laparoscopic ISCON) (Time Frame - During operation 1):
Duration of operation 1 (laparoscopic ISCON)

3. Bloodloss during operation 1 (laparoscopic ISCON) (Time Frame - During operation 1):
Bloodloss during operation 1 (laparoscopic ISCON)

4. Day of discharge after operation 1 (laparoscopic ISCON) (Time Frame - After operation 1, usually on the third post-operative day):
Day of discharge after operation 1 (laparoscopic ISCON)

5. Number of participants with anastomotic leakage after operation 2 (esophagectomy) (Time Frame - Within 30 days after operation 2):
Anastomotic leakage after operation 2 (esophagectomy)

6. Number of participants with grade 3b or higher complications after operation 2 (esophagectomy) (Time Frame - Within 30 days after operation 2):
Grade 3b (Clavien-Dindo classification) or higher complications after operation 2 (esophagectomy)

7. Number of participants with 30 day mortality after operation 2 (esophagectomy) (Time Frame - Within 30 days after operation 2):
30 day mortality after operation 2 (esophagectomy)

8. Induction of angiogenesis in tissue (Time Frame - Biopsies are taken at the start, or within 24 hours of operation 1 and operation 2. In addition, the anastomoc donut or tip of gastric tube is collected during operation 2 (esophagectomy) after formation of the anastomosis.):
Paraffin embedded sections (10µm) will be stained by immunohistochemistry against CD31 (vessel density) or smooth-muscle-actin positive pericytes to characterize vascularity

9. Induction of angiogenesis by biomarkers of microcirculation (Time Frame - Peripheral blood is taken at the start, or within 24 hours of operation 1):
A cytokine profile will be measured in the peripheral blood, consisting of VEGF, IL-8, IL-6, TNF-alpha and Ang-2

10. Redistribution of blood flow by measurement of indocyanine green (ICG) fluorescence angiography (Time Frame - During operation 1 and during operation 2 (esophagectomy)):
Redistribution of blood flow by measurement of indocyanine green (ICG)

Geprüfte Regime

Laparoscopic ischemic conditioning followed by esophagectomy:
All included patients will receive a laparoscopic ischemic conditioning followed by an esophagectomy after an interval of 12-18 days.

Quelle: ClinicalTrials.gov

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