The Efficacy of a Topical Anti-adhesive Film for Decreasing Perihepatic Adhesions in Repeat Hepatic Surgery

Study Overview
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Brief Summary
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There has been an increase in the need for repeat hepatic surgery, especially for patients with colorectal liver metastasis and hepatocellular carcinoma. Adhesions at the time of repeat surgery can lead to increased operative times, higher blood loss and even increased perioperative morbidity. Not much data exists regarding use of anti-adhesion barriers at the time of index hepatectomy and their effect on adhesions at repeat hepatectomy. This randomized controlled trial aims to evaluate the effectiveness of the use of a hyaluronan and cellulose based antiadhesive topical film at index hepatectomy in reducing perihepatic adhesions at the time of repeat hepatic surgery.

Detailed Description
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Peritoneal adhesions develop in up to 93% of patients following abdominal surgery.1 Mesothelial injury, inflammation and unbalanced fibrinolysis have been described as the primary factors leading to adhesion formation.2 Within hepatic surgery, the degree to which adhesions pose a significant challenge at the time of repeat resection often depends upon the extent of hepatectomy, hilar dissection, number of preceding liver resections, and the location of the proposed repeat partial hepatectomy. More specifically, peri-hepatic adhesions can lead to increased operative time, an increased risk of bleeding, injury to adjacent intra-abdominal organs and even higher perioperative morbidity.3 Similar to other diseases, repeat hepatectomy is often required in instances of both primary and metastatic liver cancers. This need will likely only increase in the future with continuously improving systemic chemotherapy and novel multimodality treatments. Not surprisingly, the necessary lysis of peri-hepatic adhesions has also been shown to increase operative times, by consuming as much as 50% of the operative procedure, during a repeat hepatectomy as well.4 Numerous anti-adhesion materials and barriers have been studied in colorectal,5,6,7 gynecological,8,9 neurosurgery,10 cardiac surgery,11 and otolaryngology.12 There is some data that these barriers can also be helpful in reducing operative times for repeat hepatectomy as well.13 More specifically, in a rat model, an Alg bilayer sponge application was effective in preventing peri-hepatic adhesions following a crush hepatectomy model.14 Unfortunately, there has been limited data regarding the effectiveness of any antiadhesion barriers in reducing peri-hepatic adhesions to date. SEPRA-C2T15 concluded that barrier film is helpful in reducing abdominal and perihepatic adhesions. This was done in patients with unresectable colorectal liver metastasis who underwent two stage hepatectomy and the median time to second hepatectomy was only 2 months. The primary aim of this study is to evaluate the efficacy of a topical anti-adhesion barrier film in reducing the severity of subsequent peri-hepatic adhesions at the time of repeat hepatic surgery.

Official Title
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The Efficacy of a Topical Anti-adhesive Film for Decreasing Perihepatic Adhesions in Repeat Hepatic Surgery

Conditions
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Adhesion, Liver Neoplasms

Intervention / Treatment
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* Other: Adhesion barrier


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing partial hepatectomy with high likelihood of needing repeat hepatectomy (e.g. those with colorectal liver metastasis and hepatocellular carcinoma) Patients ≥ 18 years of age. Exclusion Criteria: Patients unable to provide informed consent. Patients with hypersensitivity to Seprafilm and/or to any components of the Seprafilm. Patients who are found to have unresectable disease during surgery (additional hepatic lesions or extrahepatic metastatic disease precluding liver resection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study population will consist of all consecutive adult patients undergoing a partial hepatectomy with a high likelihood of repeat hepatectomy. These will include patients with colorectal liver metastasis and those with hepatocellular carcinoma. All patients who consent to undergo a partial hepatectomy at the Foothills Medical Center and who meet the inclusion criteria will be contacted via phone prior to their surgery by a trial research assistant in order to obtain informed consent for enrolment in the trial. Patients will be randomized with a 1:1 ratio for seprafilm vs no seprafilm group.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Seprafilm<br>Antiadhesion barrier applied | Other: Adhesion barrier<br>* Adhesion barrier application at the time of first surgery<br>|
| No Intervention: No seprafilm<br>No barrier applied | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of peri-hepatic adhesions at the time of repeat liver surgery | Evaluation will be performed at second surgery as follows: Calgary Scoring System Grade1-No adhesions, Grade2-Mild, Grade3-Moderate, Grade4-Severe adhesions, Grade5-severe adhesions with injury to other organs TORanomon Adhesion score (TORAD score): Hepatic Hilum 1-Easy: Easy for encircling the hepatoduodenal ligament (HDL) 2-Hard: Additional maneuver for encircling HDL 3-Extreme: Safe encircling of HDL is impossible Liver Surface 1-Easy: No adhesion 2-Hard: Presence of dense fibrosis or scarring tissue- hard dissection 3-Extreme): Dense scar with unclear boundary with the surrounding organs. | 0-4 years from initial surgery, time of repeat surgery will vary from patient to patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Operating time | Operating time will be measured in minutes. Hypothesis is that increased adhesions will increase the operating time. | 0-4 years from initial surgery, unpredictable - time of repeat surgery will vary from patient to patient | 
| Estimated blood loss | Estimated blood loss will be measured in milliliters. Increased adhesions lead to increase estimated blood loss. | 0-4 years from initial surgery, unpredictable - time of repeat surgery will vary from patient to patient | 
| Transfusion of blood or blood products | Will be measured in # of units, increased adhesions lead to increased blood loss and therefore increased need for blood/blood product transfusion | 0-4 years from initial surgery, unpredictable - time of repeat surgery will vary from patient to patient | 
| Duration of hepatic pedicle clamping | Will be measured in minutes. Increased adhesions and blood loss may prompt clamping of hepatic pedicle to decrease blood flow to the liver to decrease active blood loss. | 0-4 years from initial surgery, unpredictable - time of repeat surgery will vary from patient to patient | 
| Postoperative length of stay | Will be measured in days, increased adhesions may mean longer surgery and longer recovery time which will increase length of stay in the hospital for the patients | 0-4 years from initial surgery, unpredictable - time of repeat surgery will vary from patient to patient | 
| 30-day mortality and morbidity | 30-day postoperative morbidity will be classified according to the Clavien-Dindo classification (I-V). I being any deviation from normal postoperative course to V being death of patient. Postoperative morbidity will include liver failure (defined according to the International Study Group of Liver Surgery criteria), ascites, intra-abdominal fluid collection, bile leak, hemorrhage, pleural effusion, pulmonary embolism and deep venous thrombosis. Medical complications including acute myocardial infarction, cerebrovascular accident/transient ischemic attack, acute kidney injury will also be recorded. Infectious complications will include pneumonia, urinary tract infection, bloodstream infection, and surgical site infection. | 30 days after the repeat surgery which may be anywhere from 0-4 months after initial surgery |