Study of Porcine Fibrin Sealant in Preventing Cervical Anastomotic Leakage for Esophageal or Junctional Carcinoma.
Condition: Esophageal Cancer; Gastroesophageal Junction Cancer; Anastomotic Leak
MeSH terms: Anastomotic Leak
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective is to evaluate the efficacy and assess the role of Porcine Fibrin
      Sealant (Bioseal®) in preventing cervical anastomotic leakage after esophagectomy in the
      patients with resectable thoracic esophageal cancer and gastroesophageal junction cancer.
    

Detailed description: 
      Esophageal cancer (EC) is the most common cancers in the world, with more than 16,910 new
      cases and 15,690 deaths annually worldwide. Every year in China, no matter new cases or
      deaths account for more than half of the world. Currently, surgery is the most important and
      effective treatment for esophageal cancer. According to the recommendation in Chinese
      Experts' Consensus on Esophageal Cancer Radical Surgery (year 2017), the right-approach
      esophagectomy should be adopted, in order to achieve radical lymph nodes dissection and
      improve the surgical outcomes. So Mckeown procedure is recommended preferentially. However,
      esophageal resection for cancer has been associated perioperative mortality. One of the major
      perioperative complications that affect morbidity and mortality in these patients is
      esophageal anastomotic leakage. Moreover, it was reported that the leakage incidence of
      cervical anastomosis after esophageal cancer resection was significantly higher than that of
      intrathoracic anastomosis. Therefore, how to minimize the incidence of esophageal anastomotic
      leaks in esophagectomy is particularly important, especially for Mckeown surgery.

      In recent years, the prognostic outcome of esophageal cancer has been improved due to
      advances in surgical technique. However, esophageal anastomotic leakage is still one of the
      most serious complications following esophagectomy, with an incidence around 5% to 40%. For
      example, a research based on Japanese national database showed that the rate of anastomotic
      leakage after esophagectomy was 13.3%. A recent phase 3 clinical trial, the ChemoRadiotherapy
      for Oesophageal Cancer Followed by Surgery Study (CROSS) reported an anastomotic leak rate of
      26.1% after esophagectomy. Meanwhile, data from the investigator's center indicated that the
      leakage rate after esophagectomy was around 21.0%. Furthermore, anastomotic leakage following
      esophagectomy could seriously increase early mortality. According to the previous study, the
      risk of perioperative 90-day death was three times in patients with anastomotic leakage after
      esophagectomy than those without leaks (18.2% vs. 6.2%, P=0.003), and hospitalization was
      significantly increased.

      Bioseal® (Guangzhou Bioseal Biotech Co., Ltd., China) is a porcine-derived fibrin sealant
      that has been widely used in various surgical procedures to assist in hemostasis for more
      than a decade. This type of fibrin sealant is made from biologically porcine-derived thrombin
      and fibrinogen, and is designed to form a stable fibrin clot by simulating the final pathway
      of the coagulation cascade. The fibrin clot will form a gel-like material on the surface of
      the surgical wound, which can not only directly block the tissue defect, but also promote the
      healing of the wound by using the fibrin network as the matrix where the fibroblasts and
      capillary endothelial cells can proliferate to form granulation. Therefore, Bioseal® have
      been reported to be used as sealing agent as well as wound healing agent during surgery in
      some studies.

      In the recent years, some investigators have attempted to use the fibrin sealant to treat or
      prevent gastrointestinal leakage after enterectomy, gastrectomy, esophagectomy, or
      pancreaticoduodenectomy. The preliminary results show application of fibrin sealant may lower
      the chances of anastomotic leakage. Hence, it can diminish the mortality and morbidity of
      those patients with gastrointestinal reconstructions.

      In 2004, a study conducted by Nguyen both in vitro and in vivo, found that application of
      fibrin sealant over gastric bypass could reduce the postoperative anastomotic leakage. Among
      the 16 animals (pigs) undergoing laparoscopic gastric bypass, 10 cases were applied with
      fibrin sealant on their primary anastomosis, and no anastomotic leakage or related
      complications was found. Five of the other 6 cases in control group had fistula or
      intra-abdominal abscess. Moreover，the follow-up study in humans showed that 66 patients in
      whom fibrin sealant was used as reinforcement on a primary anastomosis were all free of
      anastomotic leakage. In China, some studies also reported fibrin sealant could prevent
      anastomotic leakage for patients undergoing resection of rectal carcinoma or
      pancreato-biliary tumors.

      As to esophagectomy, only few pilot studies have reported the similar attempts to prevent
      anastomotic leakage by using fibrin sealant. In 2007, Ling reported that application of
      fibrin sealant while implanting an esophageal stent under endoscopy was an effective approach
      for treating the postoperative esophageal anastomotic leakage. The studies conducted by Celal
      also showed that endoscopic treatment combined with fibrin sealant could be considered as a
      valuable option for the management of postoperative esophageal anastomotic leakage with a
      high degree of technical feasibility and safety. However, studies focusing on the role of
      fibrin sealant in the prevention of cervical leakage after esophagectomy are few.

      In 2007, a prospective clinical trial conducted by Upadhyaya enrolled 45 infant patients who
      underwent esophagectomy for congenital esophageal atresia (EA) with tracheoesophageal fistula
      (TEF). In that study, a total of 52 patients were divided into two groups. In Group A,
      patients received fibrin sealant as reinforcement on a primary end-to-end esophageal
      anastomosis. In group B, fibrin glue was not used. In the final analysis, the overall rate of
      postoperative leakage is 26.9% (12/45), including 9.1% (2/22) in group A and 43% (10/23) in
      group B (p=0.017). In 2009, Saldaña-Cortés conducted a similar research but on puerile
      esophagectomy for caustic injury. Results showed that the postoperative cervical anastomotic
      dehiscence and leakage were observed in 28.5% of patients who received fibrin sealant in the
      study group and 50% of those in the control group. Both of those two studies indicated that
      fibrin glue, when used as a sealant for cervical esophageal anastomosis, could reduce the
      risk of leakage.

      However, there is still no large-scale clinical trial investigating the use of fibrin sealant
      to prevent cervical anastomotic leakage after esophagectomy for esophageal cancer all over
      the world. The purpose of this study is to assess the role of fibrin glue (Bioseal®) in the
      prevention of leakage at the cervical esophageal anastomosis for esophageal cancer patients
      undergoing Mckeown surgery.
    

Intervention name(s): Porcine Fibrin Sealant (PFS); Surgery
Intervention type(s): Biological; Procedure
Intervention description(s): 2.5ml Porcine Fibrin Sealant will be instilled over the cervical anastomose line.; McKeown esophagectomy including open or minimally invasive esophagectomy will be performed for patients with resectable thoracic esophageal carcinoma or gastroesophageal junction cancer. Two-field lymphadenectomy with total mediastinal lymph node dissection is performed during surgery. At last, 2.5ml Porcine Fibrin Sealant will be instilled over the cervical anastomose line.
Other intervention name(s): Bioseal®; Esophagectomy
Intervention MeSH terms: Fibrin Tissue Adhesive
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment