Postoperative Heme Oxygenase Induction and Carbon Monoxide Production as a Novel Method to Assess Hepatic Regeneration and Predict Hepatic Related Morbidity After Partial Hepatectomy

Postoperative Heme Oxygenase Induction and Carbon Monoxide Production as a Novel Method to Assess Hepatic Regeneration and Predict Hepatic Related Morbidity After Partial Hepatectomy-1301GCC

The study will monitor carbon monoxide production in patients undergoing liver resection. Carbon monoxide will be checked from arterial blood gas obtained routinely as a part of the postoperative care as well as from the exhaled air of the patient through a CO detector commercially available and used as smokerlyzer helping people to stop smoking. The results of the surgical resection will be collected from the patient routinely ordered tests after liver resection including pathology of the resected part of the liver, laboratory and radiology tests. The study aims to identify the relationship between CO production and recovery after liver resection. Results of this study may help in predicting and improving results of liver resection.

Study Overview

• Status: Recruiting
• Conditions: Liver Cancer
• Intervention / Treatment: Procedure: CO Testing Pre/Post Hepatic Resection; Diagnostic test: ABG Testing Pre/Post Hepatic Resection; Diagnostic test: CT Evaluations

Detailed Description

The goal of this proposal is to elucidate the role of HO-1 induction in hepatic regeneration after partial hepatectomy (PH). There is a growing body of evidence that HO-1 induction through CO production has an important role in cellular protection and regeneration. To test this concept, we will monitor endogenous CO production in patients who undergo PH and analyze the relationship between CO production and hepatic regeneration. Using this approach we will test the following two hypotheses: (1) HO-1 induction after PH is proportional to the extent of the surgical resection, and (2) failure to appropriately induce HO-1 is associated with impaired hepatic regeneration.

Specific Aim 1: To monitor the extent of HO-1 induction (by measuring endogenous CO production) in relationship to the extent of hepatic resection 1.1 Monitor CO in exhaled air of patients before liver resection, at 4 hours and 24 hours after PH 1.2 Monitor carboxyhemoglobin(COHb) in the arterial blood gas of patients before liver resection at 4 hours and 24 hours after PH 1.3 Analyze the relationship between CO production and the extent of hepatic resection assessed by computed scans liver volumetric study at one and three months after PH, size and weight of the resected specimen and operative report.

Specific Aim 2: To analyze the relationship between HO-1 induction and the quality of post-hepatectomy liver regeneration after PH 2.1 Analyze the relationship between CO production and the quantity and quality of hepatic regeneration assessed by computed scans liver volumetric study at one and three months after PH and liver function tests after PH.

2.2 Determine the relation between postoperative liver related morbidity in patients undergoing PH and the extent of postoperative HO-1 induction.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: McKenzie E Bedra; Phone Number: 410-553-8184; Email: McKenzie.Bedra@umm.edu
• Study Contact Backup: Name: Jennifer Emel; Phone Number: 410-553-8048; Email: Jennifer.Emel@umm.edu

Study Locations

• United States
  • Maryland
    • Glen Burnie, Maryland, United States, 21601
      • Recruiting
      • University of Maryland Baltimore Washington Medical Center
      • Principal Investigator: Cherif Boutros, MD
      • Contact: Jennifer Emel; Phone Number: 410-553-8048; Email: Jennifer.Emel@umm.edu
      • Contact: McKenzie Bedra; Phone Number: 410-553-8184; Email: McKenzie.Bedra@umm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients plan to have partial liver resection for primary liver pathology or metastatic disease.
• Patients able to comprehend and willing to sign the written consent form.

Exclusion Criteria:

• Patients age less than 18
• Patients not having pathology proven liver malignancy
• Patient not able to comprehend or sign written consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Intervention Arm; CO and ABG Testing Arm

Procedure: CO Testing Pre/Post Hepatic Resection; Monitor CO in exhaled air of patients before liver resection, at 4 hours and 24 hours after PH; Diagnostic test: ABG Testing Pre/Post Hepatic Resection; Monitor carboxyhemoglobin(COHb) in the arterial blood gas of patients before liver resection at 4 hours and 24 hours after PH; Diagnostic test: CT Evaluations; Analyze the relationship between CO production and the extent of hepatic resection assessed by computed scans liver volumetric study at one and three months after PH, size and weight of the resected specimen and operative report

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure HO-1 induction by measuring endogenous CO production in relationship to the extent of hepatic resection	CO Output (ppm)	Baseline
Measure HO-1 induction by measuring endogenous CO production in relationship to the extent of hepatic resection	ABG (COHb)	Baseline
Measure HO-1 induction by measuring endogenous CO production in relationship to the extent of hepatic resection	CO Output (ppm)	4 hours post resection
Measure HO-1 induction by measuring endogenous CO production in relationship to the extent of hepatic resection	ABG (COHb)	4 hours post resection
Measure the extent of HO-1 induction by measuring endogenous CO production in relationship to the extent of hepatic resection	CO Output (ppm)	24 hours post resection
Measure the extent of HO-1 induction by measuring endogenous CO production in relationship to the extent of hepatic resection	ABG (COHb)	24 hours post resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure the relationship between HO-1 induction and the quality of post-hepatectomy liver regeneration	Volume (ml)	One month after PH and liver function tests
Measure the relationship between HO-1 induction and the quality of post-hepatectomy liver regeneration	Volume (ml)	Three months after PH and liver function tests

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Cherif Boutros, MD, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2014
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: November 20, 2019
• First Submitted That Met QC Criteria: December 9, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Hepatectomy; Arterial Blood Gas; Hepatic Regeneration; CO Production
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: HP-00054854

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Aggregate data once data is analyzed and available when the study endpoints are completed patient enrollment is completed.
• IPD Sharing Time Frame: 12 months post study completion
• IPD Sharing Access Criteria: clinicaltrials.gov
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes