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

Liver Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04641923
• Other study ID #: LIVER-SEPRAFILM
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 2022
• Est. completion date: June 2025

Study information

• Verified date: April 2021
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients undergoing partial hepatectomy with high likelihood of needing repeat hepatectomy (e.g. those with colorectal liver metastasis and hepatocellular carcinoma)

2. Patients = 18 years of age.

Exclusion Criteria:

1. Patients unable to provide informed consent.

2. Patients with hypersensitivity to Seprafilm and/or to any components of the Seprafilm.

3. Patients who are found to have unresectable disease during surgery (additional hepatic lesions or extrahepatic metastatic disease precluding liver resection

Related Conditions & MeSH terms

• Adhesion
• Liver Neoplasms
• Tissue Adhesions

Intervention

Other:
• Adhesion barrier
Adhesion barrier application at the time of first surgery

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

References & Publications (15)

Ahmad G, O'Flynn H, Hindocha A, Watson A. Barrier agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev. 2015 Apr 30;(4):CD000475. doi: 10.1002/14651858.CD000475.pub3. Review. Update in: Cochrane Database Syst Rev. 2020 M — View Citation

Arung W, Meurisse M, Detry O. Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol. 2011 Nov 7;17(41):4545-53. doi: 10.3748/wjg.v17.i41.4545. Review. — View Citation

Becker JM, Dayton MT, Fazio VW, Beck DE, Stryker SJ, Wexner SD, Wolff BG, Roberts PL, Smith LE, Sweeney SA, Moore M. Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-bl — View Citation

Caylan R, Bektas D. Preservation of the mastoid aeration and prevention of mastoid dimpling in chronic otitis media with cholesteatoma surgery using hyaluronate-based bioresorbable membrane (Seprafilm). Eur Arch Otorhinolaryngol. 2007 Apr;264(4):377-80. E — View Citation

Dupré A, Lefranc A, Buc E, Delpero JR, Quenet F, Passot G, Evrard S, Rivoire M. Use of bioresorbable membranes to reduce abdominal and perihepatic adhesions in 2-stage hepatectomy of liver metastases from colorectal cancer: results of a prospective, rando — View Citation

Fazio VW, Cohen Z, Fleshman JW, van Goor H, Bauer JJ, Wolff BG, Corman M, Beart RW Jr, Wexner SD, Becker JM, Monson JR, Kaufman HS, Beck DE, Bailey HR, Ludwig KA, Stamos MJ, Darzi A, Bleday R, Dorazio R, Madoff RD, Smith LE, Gearhart S, Lillemoe K, Göhl J — View Citation

Kaneko Y, Hirata Y, Achiwa I, Morishita H, Soto H, Kobayahsi J. Adhesion barrier reduces postoperative adhesions after cardiac surgery. Asian Cardiovasc Thorac Ann. 2012 Jun;20(3):257-62. doi: 10.1177/0218492311435154. — View Citation

Kobayashi Y, Shindoh J, Igata Y, Okubo S, Hashimoto M. A novel scoring system for evaluating the difficulty of lysis of adhesion and surgical risk at repeat hepatectomy. J Hepatobiliary Pancreat Sci. 2020 Apr;27(4):191-199. doi: 10.1002/jhbp.708. Epub 202 — View Citation

Kumar S, Wong PF, Leaper DJ. Intra-peritoneal prophylactic agents for preventing adhesions and adhesive intestinal obstruction after non-gynaecological abdominal surgery. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD005080. doi: 10.1002/14651858.CD005080 — View Citation

Mumert ML, Altay T, Couldwell WT. Technique for decompressive craniectomy using Seprafilm as a dural substitute and anti-adhesion barrier. J Clin Neurosci. 2012 Mar;19(3):455-7. doi: 10.1016/j.jocn.2011.09.004. Epub 2012 Jan 14. — View Citation

Ohta S, Toda T, Inagaki F, Omichi K, Shimizu A, Kokudo N, Hasegawa K, Ito T. The Prevention of Hepatectomy-Induced Adhesions by Bilayer Sponge Composed of Ultrapure Alginate. J Surg Res. 2019 Oct;242:286-295. doi: 10.1016/j.jss.2019.04.063. Epub 2019 May — View Citation

Schnüriger B, Barmparas G, Branco BC, Lustenberger T, Inaba K, Demetriades D. Prevention of postoperative peritoneal adhesions: a review of the literature. Am J Surg. 2011 Jan;201(1):111-21. doi: 10.1016/j.amjsurg.2010.02.008. Review. — View Citation

Shimizu A, Hasegawa K, Masuda K, Omichi K, Miyata A, Kokudo N. Efficacy of Hyaluronic Acid/Carboxymethyl Cellulose-Based Bioresorbable Membranes in Reducing Perihepatic Adhesion Formation: A Prospective Cohort Study. Dig Surg. 2018;35(2):95-103. doi: 10.1 — View Citation

Ten Broek RPG, Stommel MWJ, Strik C, van Laarhoven CJHM, Keus F, van Goor H. Benefits and harms of adhesion barriers for abdominal surgery: a systematic review and meta-analysis. Lancet. 2014 Jan 4;383(9911):48-59. doi: 10.1016/S0140-6736(13)61687-6. Epub — View Citation

Weibel MA, Majno G. Peritoneal adhesions and their relation to abdominal surgery. A postmortem study. Am J Surg. 1973 Sep;126(3):345-53. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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