Adhesion Prevention: What are my Options in Gynecological Surgery?

Surgical adhesions are pathological fibrotic connections that form between organ surfaces and the walls of surrounding body cavities following tissue trauma and ischemia.^{5, 12}

Adhesions can negatively affect surgical outcomes as they occasionally cause complications that lead to readmission. An estimated 9% of patients present with adhesion-related conditions within the first year after abdominal surgery, rising to 19% at 4 years and 35% at 10 years.⁶

Post-surgical adhesion formation is a common complication of any type of surgery, affecting 50–95% of patients regardless of the type of procedure or anatomical location.⁵

Adhesions are especially common after abdominopelvic procedures, developing after 93% of major abdominal and up to 97% of open gynecologic pelvic operations.¹³

All patients undergoing surgery are at risk of developing adhesions. However, data suggest that various factors directly or indirectly increase the likelihood of adhesion formation.¹⁴

Directly predisposing factors: genetic polymorphisms in the interleukin-I receptor antagonist, increased estrogen exposure, and endometriosis.¹⁴

Indirectly predisposing factors: insufficient fibrinolytic activity has been shown to favor adhesion formation.^{14, 15}  Thus, factors affecting the fibrinolytic system can indirectly put a patient at increased risk of post-surgical adhesions. These determinants include certain genetic polymorphisms (plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor), underlying conditions (diabetes mellitus, metabolic syndrome, hyperglycemia, obesity, depression, cancer), medication (anti-Parkinsonian or oral hormone therapy), pregnancy, and high alcohol consumption.¹⁴

Although many adhesions go unnoticed and do not cause any symptoms, some patients develop severe complications such as small bowel obstruction, chronic pain, and infertility.^{1, 16}

Adhesions can also lead to difficulties in subsequent operations – even if the patient is asymptomatic – as they change the normal anatomy. Obliterated dissection planes and abnormally conjoined organs can increase operation time and complication rates.^{3, 6} For instance, laparoscopic adhesiolysis carries a 10–25% risk of bowel injury.⁶

Some women undergoing gynecological procedures develop adhesions that affect their reproductive health, with symptoms ranging from menstrual abnormalities to infertility.^{17, 18} Indeed, adhesions account for 20–40% of cases of female infertility and can cause severe pregnancy complications such as miscarriages, premature rupture of membrane, premature delivery, or placenta accreta.^{17, 18}

Currently, no effective targeted pharmacotherapies are available to counter existing adhesions.¹⁶ If intervention is necessary, the standard approach is surgical adhesiolysis.² However, reoperation can perpetuate the problem by causing new adhesions or reformation of the existing bands due to the traumatic disruption.^2,6,9,19 Thus, the best strategy against adhesive disease is preventing adhesion formation in the initial surgery.

Current anti-adhesion measures can be classified into the following categories.⁴

1. Surgical technique optimized to minimize tissue damage

2. Adhesion barriers that block physical contact between two injured tissues or organ surfaces

3. Pharmacological agents that counteract inflammation reactions and interfere with adhesion neogenesis

However, although pharmacological agents have shown potential to reduce adhesion formation in clinical studies, off-target and adverse effects limit their use in clinical practice.⁵

Some groups have suggested that the overall risk of post-surgical adhesions should decrease in the wake of the introduction of laparoscopic surgery.⁵ However, although some preclinical and clinical data support this hypothesis, conclusive proof that this is the case in clinical practice is currently lacking. A systematic review and meta-analysis of the effect of surgical approach on the incidence of adhesion-related complications found no indication that minimally invasive techniques (e.g., laparoscopy) could improve outcomes.^2,8

Despite its limited impact on adhesion-related outcomes, meticulous surgical technique is central to an effective adhesion reduction strategy. Measures include gentle tissue handling, optimal hemostasis, avoiding tissue desiccation, and preventing thermal injury, foreign body reaction, and infection.^5,6,9

The key requirement of any adhesion barrier is that it should effectively separate traumatized peritoneal surfaces during the critical period of adhesion development in the 3–5 days after surgery, during which, peritoneal healing occurs.⁹

Barrier products range from natural to synthetic and can broadly be classified into solid barriers (membranes), gels, or solutions.⁵

Adhesion barriers have been tested extensively in clinical trials. Several studies have shown that SEPRAFILM Adhesion Barrier, a sodium hyaluronate and carboxymethylcellulose bioresorbable membrane, and ADEPT Adhesion Reduction Solution, a 4% icodextrin solution, reduce the incidence and severity of post-surgical adhesions.^10,11,18,20

For instance, a pivotal study assessed the efficacy of SEPRAFILM to reduce the incidence severity, extent and area of adhesion after myomectomy in 127 women at 19 institutions in the United States. The incidence of adhesions to the uterus (number of abdominopelvic locations adherent to the uterus) in patients treated with SEPRAFILM was 4.98 (n=49) compared to control values of 7.88 (n=48) (p<0.0001). The severity of adhesions was reduced from 2.43 (n=65) in the control group to 1.94 (n=54) in the SEPRAFILM group (p<0.01). Reduction in extent scores from 1.68 (n=65) to 1.23 (n=54) (p<0.01) were also demonstrated in the control and SEPRAFILM groups, respectively. The area of the uterus associated with adhesions was reduced from 18.72 (n=54) to 13.23 (n=65) in the patients treated with SEPRAFILM versus control patients (p<0.02). The portion of patients with adnexal adhesions to the posterior uterus was reduced from 69% (n=45) to 52% (n=28) in patients with SEPRAFILM compared to control patients (p<0.01).^10,20

Another trial compared the efficacy of ADEPT versus lactated Ringer’s solution (LRS) in reducing adhesion formation following laparoscopy. The study included 402 patients undergoing laparoscopic gynecological surgery with adhesiolysis followed by a second laparoscopy 4–8 weeks later. Significantly more patients in the ADEPT group achieved clinical success – defined as a decrease in adhesions of at least three or 30% between the first and second procedure – versus the LRS group (49% vs. 38%; p=0.018).^11,18

Several studies have shown that adhesion barriers have a favorable safety profile.^10,11,21,22 A systematic review and meta-analysis of the safety of adhesion barriers for abdominal surgery found that none of the assessed barriers were associated with an increased risk of serious adverse events.²¹ Likewise, clinical trials of SEPRAFILM and ADEPT used in patients undergoing abdominal or pelvic surgery detected no significant differences between barrier and control groups.^18,20,22