Partial Gastric Devascularization Research Articles

Laparoscopic ischemic conditioning of the stomach prior to esophagectomy induces gastric neo-angiogenesis

BackgroundThe risk of an anastomotic leakage (AL) following Ivor-Lewis esophagectomy is increased in patients with calcifications of the aorta or a stenosis of the celiac trunc. Ischemic conditioning (ISCON) of the gastric conduit prior to esophagectomy is supposed to improve gastric vascularization at the anastomotic site. The prospective ISCON trial was conducted to proof the safety and feasibility of this strategy with partial gastric devascularization 14 days before esophagectomy in esophageal cancer patients with a compromised vascular status. This work reports the results from a translational project of the ISCON trial aimed to investigate variables of neo-angiogenesis. MethodsTwenty esophageal cancer patients scheduled for esophagectomy were included in the ISCON trial. Serum samples (n = 11) were collected for measurement of biomarkers and biopsies (n = 12) of the gastric fundus were taken before and after ISCON of the gastric conduit. Serum samples were analyzed including 62 different cytokines. Vascularization of the gastric mucosa was assessed on paraffin-embedded sections stained against CD34 to detect the degree of microvascular density and vessel size. ResultsBetween November 2019 and January 2022 patients were included in the ISCON Trial. While serum samples showed no differences regarding cytokine levels before and after ISCON biopsies of the gastric mucosa demonstrated a significant increase in microvascular density after ISCON as compared to the corresponding gastric sample before the intervention. ConclusionThe data prove that ISCON of the gastric conduit as esophageal substitute induces significant neo-angiogenesis in the gastric fundus which is considered as surrogate of an improved vascularization at the anastomotic site.

P3.50: Portal hypertensive surgery for management of diffuse portomesenteric venous thrombosis - Surgical technique and long-term outcome

Introduction: Patients with diffuse portomesenteric venous thrombosis (PMVT) are often referred to the abdominal organ transplant centers particularly those with experience in gut transplantation. Despite the proven therapeutic efficacy of multivisceral transplantation (MVTx) for these complex patients, the forgotten different modalities of portal hypertensive surgery could be a better alternative particularly for those with compensated liver disease and gut varices in the milieu of a thrombophilic state. Methods: Between Aug2012 and Jan2019, a total of 28 patients referred to our center with diffuse PMVT underwent surgical intervention. Indication was history of variceal bleeding and occult varices in the setting of thrombophilia. All except 1 were adults with a mean age of 42±15 yrs. Precipitating causes of PMVT were thrombophilia (78%) and pancreatitis (18%). All patients had clinical, endoscopic and radiologic evidence of PMVT with stigmata of extra-hepatic portal hypertension. Variceal bleeding was reported in 36% patients. Type of shunt was determined intra-operative suitable visceral vascular anatomy and transplantation dictated by co-existence of advanced liver disease. Results: Portal hypertensive surgery was performed in 27 patients (96%) while MVTx was performed in one. The surgical modality was atypical non-selective portosystemic shunt in 14 patients (52%) and gastro-esophageal devascularization in the remaining 13 (48%). Partial gastric devascularization was commonly performed in patients with atypical shunt that may not completely decompress the left portal hypertensive compartment. Splenectomy was unavoidable in 4 patients. The utilization of autologous and synthetic vascular grafts are shown in Table 1. With a mean follow up of 40±26 months, overall shunt patency was radiologically documented in 78% patients. Recurrence of bleed occurred in only 1 patient (7%) despite shunt patency. Throughout the follow up period, surgical complications were minor (grade I & II) in 64% patients and major (grade III & IV) in 21% [Clavien grade]. With one mortality due to acute leukemia, all patients are currently alive with an overall survival rate of 96%. Conclusion: Portal hypertensive surgery is a viable alternative to MVTx for the management of diffuse PMVT and preserved hepatic function. Portal decompressive surgery should always be considered for thrombophilic patients with silent gut varices who are in need of life-long anticoagulation therapy.

64Cu-ATSM Hypoxia Positron Emission Tomography for Detection of Conduit Ischemia in an Experimental Rat Esophagectomy Model.

BackgroundWe designed a hypoxia-imaging modality to detect ischemia of the gastric conduit after esophagectomy.Materials and MethodsA rat esophagectomy model was created using 12-16-week-old, 300-350 g male Sprague-Dawley rats. In the operation group (n=6), partial gastric devascularization was performed by ligating the left gastric artery and the short gastric arteries and an esophagogastric anastomosis was performed. In the control group (n=6), the esophageal-gastric junction was incised and suturing was performed without gastric devascularization. Positron emission tomography (PET) images were taken using a microPET rodent model scanner, 24 h after the initial operation, after injection of 200 μCi 64Cu-diacetyl-bis (N4-methylsemicarbazone) (64Cu-ATSM) and pimonidazole 120 mg/kg. After microPET imaging, autoradiography and immunohistochemistry were performed.ResultsThe PET image revealed 64Cu-ATSM uptake at the fundus in the operation group 3 h after 64Cu-ATSM injection. The maximum percentage of the injected dose per gram of tissue was higher in the operation group (0.047±0.015 vs. 0.026±0.006, p=0.021). The fundus/liver ratio was also higher in the operation group (0.541±0.126 vs. 0.278±0.049, p=0.002). Upon autoradiography, 64Cu-ATSM uptake was observed in the fundus in the operation group, and was well-correlated to that observed on the PET image. Upon immunohistochemistry, expression of hypoxia-inducible factor 1a and pimonidazole were significantly increased at the fundus and lesser curvature compared to the greater curvature in the operation group.ConclusionHypoxia PET imaging with 64Cu-ATSM can detect ischemia in a rat esophagectomy model. Further clinical studies are needed to verify whether hypoxia imaging may be useful in humans.

Vascular conditioning of the stomach before esophageal reconstruction by gastric interposition

Gastric interposition with intrathoracic or cervical esophagogastrostomy is currently the preferred operation for reconstruction after esophagectomy. Anastomotic leaks however result from poor vascular supply to the proximal stomach. They are responsible for significant morbidity and mortality. 'Ischemic conditioning' of the interposed stomach has been proposed as a technique where the 'delay phenomenon' aims at improving the microcirculation of the gastric conduit and preventing anastomotic leakage. Experimental observations and clinical studies have been conducted to document the immediate effects and results of this approach. The aim of this work is to review the principles, pathophysiology, experimental, and clinical evidence related to vascular conditioning of the stomach prior to esophagectomy with gastric interposition and esophagogastric anastomosis. MEDLINE and PubMed were searched to identify articles related to vascular conditioning of the stomach. Cross references were added and reviewed to complete the reference list. The anatomic basis of ischemic conditioning, the prevalence of ischemic events on the gastric conduit, the methodology to assess the microcirculation before and after gastric devascularization, animal experiments, and clinical studies reported on this approach were reviewed. Ten experimental works, eleven clinical observations, four reviews, and two editorial commentaries addressing ischemic conditioning of the stomach were identified and reviewed. Experimental observations document improved microcirculation to the proximal stomach following partial gastric devascularization. Clinical reports show the feasibility and relative safety of gastric ischemic conditioning. Preliminary observations suggest potential improvements to the gastric microcirculation resulting from gastric ischemic conditioning. This approach may help prevent complications at the esophagogastric anastomosis. The actual level of evidence however cannot promote its use outside of clinical research protocols.

Laparoscopic partial gastric transection and devascularization in order to enhance its flow

BackgroundEsophagogastric fistula following an esophagectomy for cancer is very common. One of the most important factors that leads to its development is gastric isquemia. We hypothesize that laparoscopic gastric devascularization and partial transection is a safe operation that will enhance the vascular flow of the fundus of the stomach.MethodOur study included eight pigs. Each animal had two operations. In the first one, a laparoscopic gastric devascularization and mobilization took place. Vascular flow was measured previous to the procedure and immediately after it with a laser doppler (endoscopic probe). After three weeks, a second operation took place. We re-measured the vascular flow and sent a sample of gastric fundus for histopathologic evaluation.ResultsThe gastric fundus showed signs of neovascularization after both macroscopic and microscopic evaluation. These findings correlated with laser doppler measurements.ConclusionLaparoscopic gastric devascularization and partial transection is a safe procedure that increases the vascular flow of the stomach in a three week period. This finding can have a positive impact in terms of decreasing fistula formation.

Laparoscopic Gastric Ischemic Conditioning Prior to Esophagogastrectomy: Technique and Review

Esophagectomy can be associated with significant peri-operative morbidity such as leaks and strictures. Gastric ischemia as a result of gastric devascularization is one of the several contributing factors that may play a role in development of these complications. In an attempt to improve gastric tissue perfusion, a technique of gastric ischemic conditioning was proposed. For patients with esophageal cancer and at the time of laparoscopic staging, partial gastric devascularization is achieved by division of the left gastric vessels. Esophagectomy is subsequently performed several days after the gastric ischemic conditioning procedure. Our experience showed that preoperative ligation of left gastric vessels prior to esophagogastrectomy is technically feasible and safe and may decrease ischemic complications such as leaks and strictures.

Time course of necrosis/apoptosis and neovascularization during experimental gastric conditioning

Apoptosis, necrosis and neovascularization are three processes that occur during ischemic preconditioning in a range of organs. In the stomach, the effect of this preconditioning (the delay phenomenon) has helped to improve gastric vascularization prior to esophagogastric anastomosis after esophagectomy. Here we present a sequential study of the histological recovery of the gastric fundus and the phenomena of apoptosis, necrosis and neovascularization in an experimental model of partial gastric ischemia. Partial gastric devascularization was performed by ligature of the left gastric vessels in Sprague-Dawley rats. Rats were assigned to groups in accordance with their evaluation period: control, 1, 3, 6, 10, 15 and 21 days. Histological analysis, caspase-3 activity, DNA fragmentation and vascular endothelial cell proliferation (Ki-67) were measured in tissue samples after sacrifice. After 24 h of partial gastric ischemia, rates of apoptosis and necrosis were higher in the experimental groups than in controls. Tissue injury was higher 3 and 6 days post-ischemia. From day 10 after partial gastric ischemia, apoptosis and necrosis started to decrease, and on days 15 and 21 showed no differences in relation to controls. Neovascularization began between days 1 and 3, reaching its peak at 15 days after ischemia and coinciding with complete histological recovery. Both necrosis and apoptosis play a role in tissue injury during the first days after partial gastric ischemia. After 15 days, the evolution of both the histology and the neovascularization suggested that this is the optimal time for performing gastric transposition.

Gastric conditioning.

The etiology of esophagogastric anastomotic leaks is often multifactorial. However, occult ischemia of the gastric fundus is an important cause. In gastric conditioning, preliminary partial gastric devascularization is carried out 2-3 weeks before construction of the esophagogastric anastomoses. Gastric vascularity improves over this time. In animal studies, gastric conditioning has reduced the incidence of anastomotic leaks. Clinically, the concept of gastric conditioning can be used in several ways. Esophagectomy can be done at one stage, then a cervical esophagogastric anastomosis can be completed as a second-stage procedure. Pre-esophagectomy angiographic gastric artery embolization is another method of gastric conditioning. Finally, laparoscopic partial gastric devascularization can be done at the time of laparoscopic cancer staging. For gastric conditioning to be clinically useful, the benefit from reduction in leaks must be greater than the costs and morbidity of the conditioning procedure itself.

Esophagogastric Anastomotic Leaks: The Importance of Gastric Ischemia and Therapeutic Applications of Gastric Conditioning

The etiology of esophagogastric anastomotic leaks is often multifactorial. However, occult ischemia of the gastric fundus is an important cause. In gastric conditioning, preliminary partial gastric devascularization is done 2–3 weeks before construction of the esophagogastric anastomoses. Gastric vascularity improves over this time. In animal studies, gastric conditioning has reduced the incidence of anastomotic leaks. Clinically, the concept of gastric conditioning can be used in several ways. Esophagectomy can be done at one stage, and then a cervical esophagogastric anastomosis can be completed as a second-stage procedure. Preesophagectomy angiographic gastric artery embolization is another method of gastric conditioning. Finally, laparoscopic partial gastric devascularization can be done at the time of laparoscopic cancer staging. For gastric conditioning to be clinically useful, the benefit from reduction in leaks must be greater than the costs and morbidity of the conditioning procedure itself.

Ischemic conditioning (delay phenomenon) improves esophagogastric anastomotic wound healing in the rat.

Esophagogastric anastomotic leaks are a major source of morbidity after esophagectomy. Occult ischemia of the mobilized gastric fundus is an important etiological factor for this failure of healing. To test the hypothesis that ischemic conditioning (delay phenomenon) could improve esophagogastric anastomotic healing, anastomotic healing was studied in a rodent model of partial gastric devascularization. Thirty-four Sprague-Dawley rats (two groups of 17 rats) underwent partial gastric devascularization and creation of esophagogastric anastomoses. In the acute ischemia group, devascularization and anastomosis were done at the same laparotomy. In the ischemic conditioned group, devascularization was done 3 weeks before anastomosis. Gastric tissue perfusion was assessed by laser-Doppler flowmetry before and after devascularization in both groups, and 3 weeks after devascularization in the ischemic conditioned group. All rats were killed 4 days after anastomosis, and the wounds assessed for dehiscence, breaking strength, and hydroxyproline concentration. Gastric tissue perfusion, measured in tissue perfusion units (TPU) decreased immediately after devascularization (before: 73.6 +/- 12.1 TPU; after: 25.0 +/- 6.5 TPU; P < 0.001). After 3 weeks, gastric tissue perfusion returned to baseline values in the ischemic conditioned rats (before: 72.3 +/- 11.0 TPU; 3 weeks, 71.1 +/- 15.1 TPU; P < 0.80). Ischemic conditioned rats had fewer anastomotic leaks (2 vs. 9, P < 0.023) and higher anastomotic wound breaking strengths (2.35 +/- 1.05 N vs. 1.56 +/- .76 N, P < 0.02) than the acute ischemic rats. Anastomotic would hydroxy-proline concentration was not significantly different in the two groups (acute ischemic--0.111 +/- .033 mumol/mg, ischemic conditions--0.097 +/- .026 mumol/mg, P < 0.20). In this rodent model of partial gastric devascularization, ischemic conditioning (delay phenomenon) ameliorated the harmful effect of ischemic on esophagogastric anastomotic wound healing.

Gastric Distention Exacerbates Ischemia in a Rodent Model of Partial Gastric Devascularization

Occult ischemia of the mobilized gastric fundus is an important etiologic factor for esophagogastric anastomotic leaks after esophagectomy. Postoperative gastric distention is another possible predisposing factor for anastomotic leakage. We hypothesized that gastric distention could worsen gastric ischemia. To test this hypothesis, gastric tissue perfusion was studied in 20 Sprague-Dawley rats. Baseline serosal gastric tissue perfusion was measured by laser-Doppler flowmetry at a point 10 mm distal to the gastroesophageal junction. Perfusion was measured after left gastric artery occlusion, gastric distention to 20 cm water pressure, and combined left gastric artery occlusion and gastric distention. Gastric tissue perfusion (in tissue perfusion units, TPU) was 64.2 +/- 9.1 TPU at baseline measurement, 18.6 +/- 4.3 TPU after left gastric artery occlusion, 22.0 +/- 4.1 TPU after gastric distention, and 7.8 +/- 1.8 TPU after combined left gastric artery occlusion and gastric distention. Distention (P < 0.0001) and arterial occlusion (P < 0.0001) both reduced gastric tissue perfusion; of the two, arterial occlusion produced the greatest reduction in perfusion (P < 0.021). The combination of distention and arterial occlusion caused greater reduction in gastric perfusion than either factor alone (P < 0.0001). In this model, gastric distention exacerbated the ischemia produced by partial gastric devascularization. In clinical esophageal surgery, postoperative gastric distention may similarly potentiate the ischemic effects of gastric transposition for esophageal reconstruction.

Gastric distention exacerbates ischemia in a rodent model of partial gastric devascularization.

Occult ischemia of the mobilized gastric fundus is an important etiologic factor for esophagogastric anastomotic leaks after esophagectomy. Postoperative gastric distention is another possible predisposing factor for anastomotic leakage. We hypothesized that gastric distention could worsen gastric ischemia. To test this hypothesis, gastric tissue perfusion was studied in 20 Sprague-Dawley rats. Baseline serosal gastric tissue perfusion was measured by laser-Doppler flowmetry at a point 10 mm distal to the gastroesophageal junction. Perfusion was measured after left gastric artery occlusion, gastric distention to 20 cm water pressure, and combined left gastric artery occlusion and gastric distention. Gastric tissue perfusion (in tissue perfusion units, TPU) was 64.2 +/- 9.1 TPU at baseline measurement, 18.6 +/- 4.3 TPU after left gastric artery occlusion, 22.0 +/- 4.1 TPU after gastric distention, and 7.8 +/- 1.8 TPU after combined left gastric artery occlusion and gastric distention. Distention (P < 0.0001) and arterial occlusion (P < 0.0001) both reduced gastric tissue perfusion; of the two, arterial occlusion produced the greatest reduction in perfusion (P < 0.021). The combination of distention and arterial occlusion caused greater reduction in gastric perfusion than either factor alone (P < 0.0001). In this model, gastric distention exacerbated the ischemia produced by partial gastric devascularization. In clinical esophageal surgery, postoperative gastric distention may similarly potentiate the ischemic effects of gastric transposition for esophageal reconstruction.

Ischemic conditioning of the stomach may reduce the incidence of esophagogastric anastomotic leaks complicating esophagectomy: a hypothesis.

Esophagogastric anastomotic leaks are a major cause of morbidity and mortality after esophagectomy. Occult ischemia of the mobilized and partially devascularized gastric fundus is an important cause of esophagogastric leaks. The author hypothesizes that the vascularity of the gastric fundus can be improved, and anastomotic leaks reduced, by a process of ischemic conditioning (delay phenomenon). Laparoscopic partial gastric devascularization could be performed 2-3 weeks before esophagectomy. The gastric fundus would have time to re-establish an abundant blood supply before being mobilized and anastomosed to the esophagus. Since laparoscopic partial devascularization could be done at the time of laparoscopic cancer staging, gastric ischemic conditioning would not necessarily add cost or morbidity to the overall treatment of esophageal cancer. Laboratory and clinical evidence are presented to support this hypothesis.

Transplant delay will reduce anastomotic complications of gastric pull up for isolated esophageal atresia

Anastomotic dehiscence is a major source of mortality after gastric pull up reconstruction for isolated esophageal atresia. Inadequate blood supply is a leading etiologic factor for dehiscence. To enhance vascularity of the stomach, and thereby reduce anastomotic complications, laparoscopic partial gastric devascularization 14 days prior to gastric pull up is proposed. The reconstructive principle of skin flap delay is applied to the gastric pull up procedure.

Congenital isolated pulmonary valve incompetence: Neonatal presentation and early natural history

Esophagectomy with esophagogastric anastomosis is a major procedure, and its most feared complication is anastomotic leakage. Ischemic conditioning of the stomach is a method used with the aim of reducing the risk of leakage. It consists of partial gastric devascularization through embolization or laparoscopy followed by esophagectomy and anastomosis at a second stage, thus providing the time for the gastric conduit to adapt to the acute ischemia at the time of its formation. This review analyzes the information from all currently available experimental and clinical studies with the purpose of assessing the current role of the technique and to provide future recommendations.

The Inferior Mesenteric Vein as a Conduit for Variceal Decompression: A Preliminary Report

The inferior mesenteric vein — to — renal vein anastomosis with partial gastric devascularization was evaluated in ten cirrhotics. Rebleeding rates were unacceptably high, but when the appropriate indications are used, the operations may be an alternative in a limited number of patients.

The effect of intragastric pressure on gastric blood flow after partial devascularization of the stomach in cats.

The influence of intragastric pressure (IGP) on gastric blood flow was studied in cats with regional ischemia due to partial gastric devascularization, and in sham-operated cats. IGP was controlled by intragastric installation of saline. Blood flow was determined by means of the microsphere distribution technique. Increment of IGP reduced mucosal and muscularis blood flow in all areas of the stomach, both in sham-operated and devascularized cats. In areas with reduced mucosal blood flow due to devascularization, blood flow became further reduced by IGP to an extremely low flow level. The present results are pertinent to the pathogenesis of early lesser curvature ulcer or necrosis sometimes ll areas of the stomach, both in sham-operated and devascularized cats. In areas with reduced mucosal blood flow due to devascularization, blood flow became further reduced by IGP to an extremely low flow level. The present results are pertinent to the pathogenesis of early lesser curvature ulcer or necrosis sometimes ll areas of the stomach, both in sham-operated and devascularized cats. In areas with reduced mucosal blood flow due to devascularization, blood flow became further reduced by IGP to an extremely low flow level. The present results are pertinent to the pathogenesis of early lesser curvature ulcer or necrosis sometimes occurring after proximal gastric vagotomy in man.

Effect of partial gastric devascularization on mucosal blood flow and acid secretion in cats.

Partial devascularization of the stomach was performed in cats anesthetized with pentobarbital. The devascularization included all blood vessels along the greater curvature and two of the main branches of the left gastric artery. Gastric mucosal blood flow and cardiac output were determined by means of the microsphere distribution technique. The acid (H+) output from the 30th to the 60th min of pentagastrin stimulation was used as the 'acid response value'. Blood flow and acid secretion were determined before and approximately 2 h after devascularization or sham operation. A marked decrease in acid secretion and mucosal blood flow of the corpus/fundus occurred after devascularization. A high degree of correlation was found between the decrease in acid secretion and the decrease in mucosal blood flow caused by the devascularization. The regression coefficient of acid secretion on mucosal blood flow did not change significantly after devascularization.

Reduced mucosal blood flow and acid secretion related to accelerated healing of gastric ulcer in rats after omentectomy including partial gastric devascularization.

Gastric ulcers were produced in rats by local application of acetic acid to the serosal surface of the stomach. In half of the animals the greater omentum was excised just before the application of acid. Gastric mucosal blood flow was estimated by means of the (14C)-aniline clearance technique. Gastric acid secretion was determined under basal conditions and under pentagastrin stimulation. Removal of the greater omentum resulted in accelerated healing of the gastric ulcers. Maximal acid output and mucosal blood flow were found to be decreased in omentectomized animals 24 h after ulcer induction. 3 weeks later the secretion and blood flow in omentectomized animals did not differ significantly from the values of the control animals. The accelerated ulcer healing in omentectomized animals is assumed to be due to decreased acid secretion resulting from decreased mucosal blood flow following partial devascularization of the stomach.