Esophagectomy With or Without Prior Ischemic Gastric Preconditioning

Esophageal Cancer Clinical Trial

Official title:

A Multicenter, Randomized Trial of Esophagectomy and Cervical Esophagogastrostomy With (Two-stage) or Without (One-stage) Prior Ischemic Gastric Preconditioning by Laparoscopic Ligation of Left Gastric and Short Gastric Arteries

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02457299
• Other study ID #: EH15-175
• Status: Terminated
• Phase: N/A
• Start date: May 2015
• Est. completion date: November 2016

Study information

• Verified date: August 2019
• Source: NorthShore University HealthSystem
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multi-center, randomized prospective clinical trial involves esophageal cancer patients who are surgical candidates. Patients will be randomized either to the one stage or the two stage esophagectomy procedure. Surgical, oncology outcomes, quality of life and cost analysis from both types of procedure will be reviewed and compared.

Description:

Esophagectomy with gastric pull-up reconstruction is the current preferred operation for either benign or malignant esophageal disease requiring resection. One of the major complications of an esophagectomy with gastric pull-up reconstruction is esophagus-stomach connection (gastric conduit) failure, which carries significant morbidity and mortality. Many factors contribute to the development of gastric conduit failure, but relative decreased blood flow (ischemia) of the tip of the gastric conduit is believed to be one major factor. This is due to the sacrifice of 3 of the 5 gastric blood supplies leaving the tip of the conduit to rely on collateral vessels. In an effort to improve perfusion to the gastric conduit and to minimize ischemia, the relatively novel approach of ischemic gastric preconditioning was devised, but without concrete evidence to show an advantage of a reduction in gastric conduit failures.

Patients meeting eligibility criteria and agree to participation in the study will be randomized to either a esophagectomy with (two-stage) or without (one-stage) ischemic gastric preconditioning and the incidence of gastric conduit failure will be compared. Those randomized to a two-stage procedure will have laparoscopic staging and ischemic gastric conditioning and pyloric Botox injection done 7-10 days prior to an esophagectomy and those randomized to a one-stage procedure will only have the esophagectomy performed.

Validated quality of life (QOL) questionnaires will be completed at the preoperative visit as well as on the day of discharge and at postoperative follow-up timepoints: 3 weeks, 3 months, 6 months, 12 months and 24 months. Data collection will be mostly collected through electronic medical record review and will include, but is not limited to: demographic data; imaging and laboratory values; past medical, surgical and social history; inpatient and intraoperative data; and vitals signs. Patients will be assessed for adverse events throughout study participation.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject is willing and able to provide written informed consent

• Subject is a candidate for esophagectomy with or without gastric pre-conditioning procedure per thoracic surgeon

• Patient is at least 18 years old

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Cancer stage: T1-2-3 N0M0, Locally advanced, T2-3 N1M0 based on American Joint Committee on Cancer (AJCC) 7th Edition by the oncologist

• No definitive radiological evidence of distant metastases as evaluated by CT or PET/CT scan

• Subject is willing and able to comply with the study procedures and complete the entire study as specified in the protocol, including follow-up visits.

Exclusion Criteria:

• Patients < 18 years old

• History of invasive cancer within the past 5 years, (exceptions: non melanoma skin cancer, in situ cancers)

• Prior upper abdominal surgeries performed open and/or laparoscopic; such as but not limited to Nissen fundoplication, gastrectomy, bariatric surgery, hiatus hernia repair.

• Subject is participating in another investigational trial

• Subject is pregnant or has plans to become pregnant during the study period or is currently breastfeeding

• Subject is part of the site personnel directly involved with this study

• Subject is a family member of the investigational study staff

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Procedure:
• Two Stage Esophagectomy
Patients will undergo laparoscopic staging and ischemic gastric conditioning and pyloric Botox injection 7-10 days prior to an esophagectomy with gastric pull-up reconstruction
• One Stage Esophagectomy
Patients will undergo an esophagectomy with gastric pull-up reconstruction without any preconditioning.

Locations

Country	Name	City	State
United States	NorthShore University HealthSystem	Evanston	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
NorthShore University HealthSystem

Country where clinical trial is conducted

United States, 

References & Publications (15)

Akiyama S, Kodera Y, Sekiguchi H, Kasai Y, Kondo K, Ito K, Takagi H. Preoperative embolization therapy for esophageal operation. J Surg Oncol. 1998 Dec;69(4):219-23. — View Citation

Bludau M, Hölscher AH, Vallböhmer D, Gutschow C, Schröder W. Ischemic conditioning of the gastric conduit prior to esophagectomy improves mucosal oxygen saturation. Ann Thorac Surg. 2010 Oct;90(4):1121-6. doi: 10.1016/j.athoracsur.2010.06.003. — View Citation

Cooke DT, Lin GC, Lau CL, Zhang L, Si MS, Lee J, Chang AC, Pickens A, Orringer MB. Analysis of cervical esophagogastric anastomotic leaks after transhiatal esophagectomy: risk factors, presentation, and detection. Ann Thorac Surg. 2009 Jul;88(1):177-84; discussion 184-5. doi: 10.1016/j.athoracsur.2009.03.035. — View Citation

Cuenca-Abente F, Assalia A, del Genio G, Rogula T, Nocca D, Ueda K, Gagner M. Laparoscopic partial gastric transection and devascularization in order to enhance its flow. Ann Surg Innov Res. 2008 Jul 7;2:3. doi: 10.1186/1750-1164-2-3. — View Citation

Hölscher AH, Schneider PM, Gutschow C, Schröder W. Laparoscopic ischemic conditioning of the stomach for esophageal replacement. Ann Surg. 2007 Feb;245(2):241-6. — View Citation

Honkoop P, Siersema PD, Tilanus HW, Stassen LP, Hop WC, van Blankenstein M. Benign anastomotic strictures after transhiatal esophagectomy and cervical esophagogastrostomy: risk factors and management. J Thorac Cardiovasc Surg. 1996 Jun;111(6):1141-6; discussion 1147-8. — View Citation

Nguyen NT, Longoria M, Sabio A, Chalifoux S, Lee J, Chang K, Wilson SE. Preoperative laparoscopic ligation of the left gastric vessels in preparation for esophagectomy. Ann Thorac Surg. 2006 Jun;81(6):2318-20. — View Citation

Oezcelik A, Banki F, DeMeester SR, Leers JM, Ayazi S, Abate E, Hagen JA, Lipham JC, DeMeester TR. Delayed esophagogastrostomy: a safe strategy for management of patients with ischemic gastric conduit at time of esophagectomy. J Am Coll Surg. 2009 Jun;208(6):1030-4. doi: 10.1016/j.jamcollsurg.2009.02.055. Epub 2009 Apr 24. — View Citation

Reavis KM, Chang EY, Hunter JG, Jobe BA. Utilization of the delay phenomenon improves blood flow and reduces collagen deposition in esophagogastric anastomoses. Ann Surg. 2005 May;241(5):736-45; discussion 745-7. — View Citation

Schröder W, Hölscher AH, Bludau M, Vallböhmer D, Bollschweiler E, Gutschow C. Ivor-Lewis esophagectomy with and without laparoscopic conditioning of the gastric conduit. World J Surg. 2010 Apr;34(4):738-43. doi: 10.1007/s00268-010-0403-x. — View Citation

Sepesi B, Swisher SG, Walsh GL, Correa A, Mehran RJ, Rice D, Roth J, Vaporciyan A, Hofstetter WL. Omental reinforcement of the thoracic esophagogastric anastomosis: an analysis of leak and reintervention rates in patients undergoing planned and salvage esophagectomy. J Thorac Cardiovasc Surg. 2012 Nov;144(5):1146-50. doi: 10.1016/j.jtcvs.2012.07.085. Epub 2012 Aug 28. — View Citation

Urschel JD. Ischemic conditioning of the rat stomach: implications for esophageal replacement with stomach. J Cardiovasc Surg (Torino). 1995 Apr;36(2):191-3. — View Citation

Varela E, Reavis KM, Hinojosa MW, Nguyen N. Laparoscopic gastric ischemic conditioning prior to esophagogastrectomy: technique and review. Surg Innov. 2008 Jun;15(2):132-5. doi: 10.1177/1553350608317352. Epub 2008 May 13. Review. — View Citation

Wormuth JK, Heitmiller RF. Esophageal conduit necrosis. Thorac Surg Clin. 2006 Feb;16(1):11-22. Review. — View Citation

Yetasook AK, Leung D, Howington JA, Talamonti MS, Zhao J, Carbray JM, Ujiki MB. Laparoscopic ischemic conditioning of the stomach prior to esophagectomy. Dis Esophagus. 2013 Jul;26(5):479-86. doi: 10.1111/j.1442-2050.2012.01374.x. Epub 2012 Jul 20. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of participants with gastric conduit failures as a measure of safety and tolerability in the one-stage esophagectomy as compared with the two-stage esophagectomy.		7-10 days
Secondary	Mortality rates in both groups		30-90 days
Secondary	Cost effectiveness analysis of treatment in one-stage versus two-stage esophagectomy		Hospital inpatient stay, an expected average of a week
Secondary	Nutritional status of one-stage versus two-stage esophagectomy	This will be determined by prealbumin and albumin values	Within 30-days of surgery as compared with 3 and 12 month follow-up time points
Secondary	Quality of Life (QOL) scores of patients in both arms		baseline and up to 24 months postoperatively