Laparoscopic Gastric Ischemic Conditioning Prior to Minimally Invasive Esophagectomy, the Logic Trial

DARMARAJAH VEERAMOOTOO, MB BS MRCS MD, ANGELA C SHORE, PhD, SHAHJEHAN A WAJED, MA BM BCh MChir FRCS. Department of Upper Gastro-Intestinal Surgery, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom. Institute of Biomedical and Clinical Sciences, University of Exeter, Exeter, United Kingdom.

Introduction:
Minimally invasive esophagectomy (MIE) is recognised as a valid, less traumatic alternative to open surgery for the management of resectable esophago-gastric cancer. However, a significant incidence of ischemia-related gastric conduit failure (GCF) is observed with this approach. Laparoscopic Ischemic conditioning (LIC) of the stomach by ligation of the left gastric vessels two weeks prior to MIE, through a potential improvement of conduit perfusion, is believed to have a protective role. The purpose of this project was therefore to evaluate whether ischemic conditioning improved eventual conduit perfusion.

Methods:
A randomised controlled trial was designed to compare MIE with LIC at two weeks (Lig) against MIE without LIC (Non-lig). The MIE technique is a three-stage procedure consisting of a thoracoscopic phase, laparoscopy and extra-corporeal fashioning of the gastric conduit and finally a cervical anastomosis. This ethically-approved project began in May 2009 and was offered to all consecutive consenting patients. A multifactorial analysis of variance allowed block randomisation of subjects into the two trial arms. The main outcome measure was perfusion recorded from the serosal surface of the stomach by validated laser Doppler fluximetry. Areas of interest were the fundus (F) and greater curve (GC) and measurements were carried out at routine staging laparoscopy before and after intervention and again at every stage of an MIE (Laparoscopy = baseline, exteriorisation of stomach, conduit formation and delivery at neck). Mean perfusion values were compared using Wilcoxon matched pairs test; and a perfusion coefficient measured as a ratio at stage of MIE over baseline was used for statistical analysis (Mann Whitney U-test).

Results:
16 patients were recruited prior to an interim analysis of the trial data, 8 in each arm. At staging laparoscopy perfusion at F was higher than at GC (603.3±153.0 v 543.9±167.6; p=0.016). In the Lig cohort an apparent rise in perfusion at GC is observed post intervention (538.0±174.0 v 496.8±184.5, p=0.176). At MIO, baseline perfusion is comparable for both arms; F being higher than GC but a significant drop is noted once stomach is mobilised and exteriorised (F: Lap. 539.7±161.6 v outside 207.5±73.7, p=0.0001 and GC: Lap. 489.3±112.8 v outside 323.4±92.3, p=0.001). Perfusion at GC is now higher than F (p=0.001). This trend is repeated at the conduit stage. Once delivered at the neck, perfusion ratio of the conduit is about 38% of baseline (range=18.1 to 67.4). However there is no difference between the Lig (38.3±12.0) and Non-lig (37.7±16.8) cohorts (p=0.798).

Conclusions:
This study demonstrates the effect of stomach devascularisation is such that conduit perfusion is only around 1/3 of that present initially. The interim analysis revealed no effect of ischemic conditioning by ligation of the left gastric vessels on conduit perfusion. If the effects were as great as reported in historical series, a difference in perfusion would have been expected even at this interim analysis.