Laparoscopic Ischemic Conditioning Prior to Esophagectomy

NCT ID: NCT03896399

Last Updated: 2022-01-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-09
• Study Completion Date: 2022-12-31

Brief Summary

This is a two center phase II prospective single-arm safety and feasibility trial for 20 patients with resectable esophageal carcinoma with an increased risk for anastomotic leakage, as based upon UCS and NASCET calcification scores on pre-op CT-scan. In these patients, laparoscopic ischemic conditioning is performed 12-18 days before an Ivor-Lewis esophagectomy. The primary outcome is all complications grade 2 and higher (Clavien-Dindo classification) occurring during or after the laparoscopic ischemic conditioning. Secondary outcomes are complications after the esophagectomy, and the induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow by measurement of indocyanine green (ICG) fluorescence angiography.

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).

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Laparoscopic ischemic conditioning followed by esophagectomy

Intervention Type: PROCEDURE

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

Interventions

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital of Cologne

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

Richard van Hillegersberg

Professor, surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard van Hillegersberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Utrecht, dept. of Surgery

Wolfgang Schröder, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Cologne, department of Surgery

Locations

University Hospital of Cologne

Cologne, North Rhine-Westphalia, Germany

Site Status: RECRUITING

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status: RECRUITING

Countries

Germany; Netherlands

Central Contacts

Eline De Groot, MD

Role: CONTACT

e.m.degroot-26@umcutrecht.nl

+316 49391569

Isabel Bartella, MD, PhD

Role: CONTACT

isabel.bartella@uk-koeln.de

+492214784803

Facility Contacts

Isabel Bartella, MD, PhD

Role: primary

isabel.bartella@uk-koeln.de

+49 (0)221-478 4803

Wolfgang Schröder, MD, PhD

Role: backup

wolfgang.schroeder@uni-koeln.de

+49 (0)221-478 4803

Arjen van der Veen, MD

Role: primary

a.vanderveen-12@umcutrecht.nl

+31 (0)88-755 8507

Richard van Hillegersberg, MD, PhD

Role: backup

r.vanhillegersberg@umcutrecht.nl

+31 (0)88-755 8074

References

Veen AV, Schiffmann LM, de Groot EM, Bartella I, de Jong PA, Borggreve AS, Brosens LAA, Santos DPD, Fuchs H, Ruurda JP, Bruns CJ, van Hillegersberg R, Schroder W. The ISCON-trial protocol: laparoscopic ischemic conditioning prior to esophagectomy in patients with esophageal cancer and arterial calcifications. BMC Cancer. 2022 Feb 5;22(1):144. doi: 10.1186/s12885-022-09231-x.

Reference Type: DERIVED

PMID: 35123419 (View on PubMed)

Other Identifiers

NL67819.041.18

Identifier Type: -

Identifier Source: org_study_id