A Novel Technique to Improve Anastomotic Perfusion Prior to Esophageal Surgery: Hybrid Ischemic Preconditioning of the Stomach. Preclinical Efficacy Proof in a Porcine Survival Model.

Manuel Barberio,Yusef Moulla,Michele Diana,Vincent Agnus,Jacques Marescaux,Veronique Lindner,Boris Jansen-Winkeln,Margherita Pizzicannella,Eric Felli,Ines Gockel,Raoul Pop,Andrea Baiocchini,Bernard Geny

doi:10.3390/cancers12102977

Abstract

Simple SummaryEsophagectomy has a high rate of anastomotic complications thought to be caused by poor perfusion of the gastric graft, which is used to restore the continuity of the gastrointestinal tract. Ischemic gastric preconditioning (IGP), performed by partially destroying preoperatively the gastric vessels either by means of interventional radiology or surgically, might improve the gastric conduit perfusion. Both approaches have downsides. The timing, extent and mechanism of IGP remain unclear. A novel hybrid IGP method combining the advantages of the endovascular and surgical approach was introduced in this study. IGP improves unequivocally the mucosal and serosal blood-flow at the gastric conduit fundus by triggering new vessels formation. The proposed timing and extent of IGP were efficacious and might be easily applied to humans. This novel minimally invasive IGP technique might reduce the anastomotic leak rate of patients undergoing esophagectomy, thus improving their overall oncological outcome.Esophagectomy often presents anastomotic leaks (AL), due to tenuous perfusion of gastric conduit fundus (GCF). Hybrid (endovascular/surgical) ischemic gastric preconditioning (IGP), might improve GCF perfusion. Sixteen pigs undergoing IGP were randomized: (1) Max-IGP (n = 6): embolization of left gastric artery (LGA), right gastric artery (RGA), left gastroepiploic artery (LGEA), and laparoscopic division (LapD) of short gastric arteries (SGA); (2) Min-IGP (n = 5): LGA-embolization, SGA-LapD; (3) Sham (n = 5): angiography, laparoscopy. At day 21 gastric tubulation occurred and GCF perfusion was assessed as: (A) Serosal-tissue-oxygenation (StO2) by hyperspectral-imaging; (B) Serosal time-to-peak (TTP) by fluorescence-imaging; (C) Mucosal functional-capillary-density-area (FCD-A) index by confocal-laser-endomicroscopy. Local capillary lactates (LCL) were sampled. Neovascularization was assessed (histology/immunohistochemistry). Sham presented lower StO2 and FCD-A index (41 ± 10.6%; 0.03 ± 0.03 respectively) than min-IGP (66.2 ± 10.2%, p-value = 0.004; 0.22 ± 0.02, p-value < 0.0001 respectively) and max-IGP (63.8 ± 9.4%, p-value = 0.006; 0.2 ± 0.02, p-value < 0.0001 respectively). Sham had higher LCL (9.6 ± 4.8 mL/mol) than min-IGP (4 ± 3.1, p-value = 0.04) and max-IGP (3.4 ± 1.5, p-value = 0.02). For StO2, FCD-A, LCL, max- and min-IGP did not differ. Sham had higher TTP (24.4 ± 4.9 s) than max-IGP (10 ± 1.5 s, p-value = 0.0008) and min-IGP (14 ± 1.7 s, non-significant). Max- and min-IGP did not differ. Neovascularization was confirmed in both IGP groups. Hybrid IGP improves GCF perfusion, potentially reducing post-esophagectomy AL.

Highlights

Esophageal cancer is ranked seventh worldwide among all cancers, in terms of incidence (572,000 new cases) and ranked sixth for mortality rates (509,000 deaths) [1]
30] that ischemic gastric preconditioning (IGP) improves gastric conduit fundus (GCF) perfusion, provided that a minimum delay of 2 to 3 weeks is observed between IGP and gastric conduit formation
The results of the present study unequivocally demonstrate that IGP, applied 3 weeks prior to gastric tubulation, improves mucosal and serosal perfusion at the GCF, assessed by means of quantitative optical imaging technologies

Summary

Introduction

Esophageal cancer is ranked seventh worldwide among all cancers, in terms of incidence (572,000 new cases) and ranked sixth for mortality rates (509,000 deaths) [1]. Esophageal resection is a major surgical high-risk procedure with considerable complication rates [3], which may negatively impact the overall oncological outcome as well as the quality of life of patients [4,5]. The incidence of anastomotic leak (AL) is relevantly higher, when compared to other gastrointestinal anastomoses [6]. Some risk factors to develop AL are not modifiable and include preexisting relevant comorbidities [7] (e.g., hypertension, renal failure, congestive heart failure, smoking), and probably most importantly the presence of substantial atherosclerosis [8]

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