In this updated systematic review and meta-analysis, we show that Seprafilm® use in elective gastrointestinal/colorectal surgery is associated with a reduction in postoperative adhesive small bowel obstruction but did not translate into a reduction in clinically significant adhesive bowel obstruction requiring surgical adhesiolysis.
This represents the first subgroup analysis of elective gastrointestinal surgery (both open and laparoscopic) which overcomes the heterogeneity brought about in previous systematic reviews, where most of the included articles studied gynaecology or pelvic surgery. Narrowing the focus onto clinically significant postoperative intestinal obstruction also allows us to answer the question on the utility of Seprafilm® in surgical practice today.
Adhesions are an inevitable consequence of intra-abdominal surgeries and complications associated with postoperative adhesions continue to challenge the health care system. In particular, colorectal surgery has been noted to have high rates of ASBO (21). Apart from meticulous tissue handling and minimally invasive surgical techniques, physical barriers represent the only widely accepted methods of postoperative adhesion prevention(1).
With the increase in minimally invasive colorectal surgery performed today, our sub-analysis of laparoscopic operations is relevant. Our results support previous reports that Seprafilm® can reduce intestinal obstruction after laparoscopic surgery, (17) where the reduced trauma from laparoscopic surgery has been shown to prevent adhesion formation in itself(22). By removing this confounder, it gives us confidence that Seprafilm® will continue to remain relevant.
Much has been discussed around the technical difficulties in applying Seprafilm® laparoscopically(23). The thin film understandably is difficult to insert via a laparoscopic port, being easily torn. Thereafter highly skilled laparoscopic skills required to unfold it in the abdominal cavity and accurately applied in the targeted area. when the Seprafilm® gets wet, its surface becomes sticky, so once it enters the abdominal cavity, it is extremely difficult to remove laparoscopically and separate from other organs. Because of these shortcomings in the application of Seprafilm® in laparoscopic surgery, some studies have improved the method of laparoscopic placement(23, 24). These include the introduction of a reducer sleeve to protect the sheets as they are inserted, to dividing the Seprafilm® sheet into smaller pieces that can be more easily manipulated into its intended position without moistening.
The inability to show a significant reduction in clinically important small bowel obstruction episodes despite a reduced bowel obstruction incidence hint at the complex physiological pathways involved in producing adhesions. This is inevitably due to the interplay between individual patient, surgical and disease factors. Therefore, the authors hypothesize that there could be a select group of patients such as recurrent small bowel obstruction patients, in whom Seprafilm® may prove to be useful. This deserves further study.
We acknowledge that our dataset spanned two decades which portends a degree of heterogeneity that deserves consideration. It follows that Seprafilm® is effective only at the site of placement, as the anti-adhesion properties of the film-based barrier depend on separation between the intra-abdominal organs and the mesothelium. Our studies yielded various placement strategies including amount of Seprafilm® and the location placed. This is a limitation and while we did not prove Seprafilm® as an adhesion barrier could translate into a reduction in reoperation rates, deserves further study.
Our analysis did not yield any significant red flags about the safety of Seprafilm®, apart from the well-known association with anastomotic leaks when placed on anastomoses. Seprafilm® has the characteristics of non-immunogenicity and good biocompatibility but its effects on postoperative liver function, renal function, and other physiological indexes of gastrointestinal neoplasms patients remain unclear (10). The significance of the temporary increase of serum creatinine in the early stage after Seprafilm® application seen in some patients remains unanswered(25, 26). Reassuringly, there is no difference in the results of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, which suggests that Seprafilm® does not cause a systemic inflammatory response (11).
Isolated case reports (27–31) have nonetheless described a paradoxically intense intra-abdominal inflammatory reaction at the site corresponding to Seprafilm® application which can make re-entry unsafe within the first seven days. This could potentially make a relook laparotomy in the event of complications such as an anastomotic leak even riskier. These accounts have described a foreign body reaction causing intense inflammation, with foreign body granulomas found on biopsy(29). This dense, thick, glue-like mass can envelop the underlying small intestine and transverse colon with resultant high risk of iatrogenic enterotomy(30). This process of aseptic peritonitis is usually accompanied by a fever and raised neutrophil counts within 4–7 days after receiving Seprafilm® during laparotomy (27).
This foreign body reaction can alternatively create collections of sterile intra-abdominal fluids were identified in three subjects following the use of Seprafilm® in colorectal surgery (29). These case studies were included in the retrospective study at the Cleveland Clinic which found use of Seprafilm® in restorative proctocolectomy was associated with pelvic collections (32, 33). Another 10-year observational retrospective study found a significant increase in postoperative fluid collections after colectomies and gynaeological debulking surgeries (26). While reports of this kind remain uncommon in the two decades of Seprafilm® use, further attention is required to define the risk factors for such adverse effects.