Adhesion reformation and the limited translational value of experiments with adhesion barriers: A systematic review and meta-analysis of animal models.

Today, 40-66% of elective procedures in general surgery are reoperations. During reoperations, the need for adhesiolysis results in increased operative time and a more complicated convalescence. In pre-clinical evaluation, adhesion barriers are tested for their efficacy in preventing 'de novo' adhesion formation, However, it is unknown to which extent barriers are tested for prevention of adhesion reformation. The aim of this systematic review and meta-analysis is to assess the efficacy of commercially available adhesion barriers and laparoscopic adhesiolysis in preventing adhesion reformation in animal models. Pubmed and EMBASE were searched for studies which assessed peritoneal adhesion reformation after a standardized peritoneal injury (in the absence of an intra-peritoneal mesh), and reported the incidence of adhesions, or an adhesion score as outcome. Ninety-three studies were included. No study met the criteria for low risk of bias. None of the commercially available adhesion barriers significantly reduced the incidence of adhesion reformation. Three commercially available adhesion barriers reduced the adhesion score of reformed adhesions, namely Seprafilm (SMD 1.38[95% CI]; p < 0.01), PEG (SMD 2.08[95% CI]; p < 0.01) and Icodextrin (SMD 1.85[95% CI]; p < 0.01). There was no difference between laparoscopic or open adhesiolysis with regard to the incidence of adhesion reformation (RR 1.14[95% CI]; p ≥ 0.05) or the adhesion score (SMD 0.92[95% CI]; p ≥ 0.05). Neither currently commercially available adhesion barriers, nor laparoscopic adhesiolysis without using an adhesion barrier, reduces the incidence of adhesion reformation in animal models. The methodological quality of animal studies is poor.

Cost-effectiveness of the prevention of adhesions and adhesive small bowel obstruction after colorectal surgery with adhesion barriers: a modelling study.

Background: Adhesion barriers have proven to reduce adhesion-related complications in colorectal surgery. However, barriers are seldom applied. The aim of this study was to determine the cost-effectiveness of adhesion barriers in colorectal surgery. Methods: A decision-tree model was developed to compare cost-effectiveness of no adhesion barrier with the use of an adhesion barrier in open and laparoscopic surgery. Outcomes were incidence of clinical consequences of adhesions, direct healthcare costs, and incremental cost-effectiveness ratio per adhesion prevented. Deterministic and probabilistic sensitivity analyses were performed. Results: Adhesion barriers reduce adhesion incidence and incidence of adhesive small bowel obstruction in open and laparoscopic surgery. Adhesion barriers in open surgery reduce costs compared to no adhesion barrier ($4376 versus $4482). Using an adhesion barrier in laparoscopic procedures increases costs by $162 ($4482 versus $4320). The ICER in the laparoscopic cohort was $123. Probabilistic sensitivity analysis showed 66% and 41% probabilities of an adhesion barrier reducing costs for open and laparoscopic colorectal surgery, respectively. Conclusion: The use of adhesion barriers in open colorectal surgery is cost-effective in preventing adhesion-related problems. In laparoscopic colorectal surgery, an adhesion barrier is effective at low costs.

The Efficacy of an Ultrapure Alginate Gel in Reducing Adhesion Formation in a Rat Model of Blood Contamination.

BACKGROUND: Formation of peritoneal adhesions is the most frequent complication of abdominal and pelvic surgery and comprises a lifelong risk of adhesion-related morbidity and mortality. Some of the existing antiadhesive barriers are less effective in the presence of blood. In this study, we investigate the efficacy and safety of ultrapure alginate gel in the presence of blood. METHODS: In experiment 1 (30 rats), 1 mL ultrapure alginate gel was compared with no intervention in a model of cecal abrasion and persisting peritoneal bleeding by incision of the epigastric artery. In experiment 2 (30 rats), 2 mL ultrapure alginate gel was compared with no intervention in a model where a 1 mL blood clot was instilled intra-abdominally and a cecal resection was performed. The primary endpoint was the incidence and severity of adhesions after 14 d. RESULTS: In experiment 1, seven of 15 rats in the experimental group had intra-abdominal adhesions compared with 13 of 15 rats in the control group (P = 0.05); 3 of 15 rats had adhesions at the site of injury compared with 12 of 15 rats in the control group (P < 0.01). The severity and extent of adhesions was also reduced (P < 0.01). In experiment 2, 12 of 13 rats had adhesions compared with 13 of 14 rats in the control group (P = 1.00). CONCLUSIONS: Ultrapure alginate gel reduces the incidence and severity of adhesion in the presence of persisting bleeding, but not in a model of cecal resection and blood clot.

Risk of Pain and Gastrointestinal Complaints at 6Months After Elective Abdominal Surgery.

The incidence of chronic postoperative abdominal pain (CPAP) after abdominal surgery is substantial and decreases overall quality of life. One in 3 patients report pain-related interference with mood, sleep, and enjoyment of life and 12% visit the emergency department for pain-related symptoms. Previous studies lack data on preoperative health and pain status or are limited by small patient samples. The aim of this study was to assess risk factors for CPAP and gastrointestinal complaints 6 months after surgery. A prospective cohort study was performed including patients undergoing an elective laparotomy or laparoscopy at a tertiary referral center. Relevant patient, pain, surgical, and medical data as well as the Gastrointestinal Symptom Rating Scale (GSRS) were assessed before, during, and after hospital stay and at the outpatient clinic until 6 months after discharge. Linear and logistic regression analysis were used to assess risk factors. Of 518 included patients, 184 (36%) had CPAP. The median GSRS score was 5 (interquartile range = 3-10). The presence of preoperative pain for <3 months (odds ratio [OR] = 2.69, P = .016) or >3 months (OR = 3.99, P = .000), use of opioid analgesia preoperatively (OR = 3.54, P = .001), severe adhesions underneath the incision (OR = 1.63, P = .040), and the numeric rating scale pain score on postoperative day 2 (OR = 1.23, P = .004) independently increased the risk for chronic abdominal pain. Chronic pancreatitis as indication for surgery (B = 4.20, P = .03), ≥3 previous abdominal operations (B = 1.03, P = .03), presence of pain >3 months before surgery (B = 1.61, P < .01), upper gastrointestinal tract as the anatomic location of surgery (B = 1.43, P = .03), and a higher preoperative GSRS score (B = .36, P < .01) independently increased the GSRS score 6 months after surgery. The duration and severity of preoperative pain and more severe acute postoperative pain were the most relevant risk factors for CPAP. The number of operations and the anatomic location of the operation showed to be important risk factors for increasing the number of gastrointestinal complaints. Perspective: This prospective observational study shows the incidence and risk factors for CPAP after major abdominal surgery. Preoperative pain-related factors were associated with the occurrence of CPAP.

A Shared Decision Approach to Chronic Abdominal Pain Based on Cine-MRI: A Prospective Cohort Study.

OBJECTIVES: Chronic abdominal pain develops in 11-20% of patients undergoing abdominal surgery, partly owing to post-operative adhesions. In this study we evaluate results of a novel diagnostic and therapeutic approach for pain associated with adhesions. METHODS: Prospective cohort study including patients with a history of abdominal surgery referred to the outpatient clinic of a tertiary referral center for the evaluation of chronic abdominal pain. Subgroups were made based on outcome of adhesion mapping with cine-MRI and shared decision making. In operatively managed cases, anti-adhesion barriers were applied after adhesiolysis. Long-term results for pain were evaluated by a questionnaire. RESULTS: A total of 106 patients were recruited. Seventy-nine patients had adhesions on cine-MRI, 45 of whom underwent an operation. Response rate to follow-up questionnaire was 86.8%. In the operative group (Group 1), the number of negative laparoscopies was 3 (6%). After a median of 19 (range 6-47) months follow-up, 80.0% of patients in group 1 reported improvement of pain, compared with 42.9% in patients with adhesions on cine-MRI who declined surgery (group 2), and 26.3% in patients with no adhesions on cine-MRI (group 3), P = 0.002. Consultation of medical specialists was significantly lower in group 1 compared with groups 2 and 3 (35.7 vs. 65.2 vs. 58.8%; P = 0.023). CONCLUSION: We demonstrate long-term pain relief in two-thirds of patients with chronic pain likely caused by adhesions, using cine-MRI and a shared decision-making process. Long-term improvement of pain was achieved in 80% of patients who underwent surgery with concurrent application of an anti-adhesion barrier.

Multicenter Observational Study of Adhesion Formation After Open-and Laparoscopic Surgery for Colorectal Cancer.

OBJECTIVE: The aim of this study was to compare adhesion formation after laparoscopic and open colorectal cancer resection. SUMMARY OF BACKGROUND DATA: After colorectal surgery, most patients develop adhesions, with a high burden of complications. Laparoscopy seems to reduce adhesion formation, but evidence is poor. Trials comparing open- and laparoscopic colorectal surgery have never assessed adhesion formation. METHODS: Data on adhesions were gathered during resection of colorectal liver metastases. Incidence of adhesions adjacent to the original incision was compared between patients with previous laparoscopic- and open colorectal resection. Secondary outcomes were incidence of any adhesions, extent and severity of adhesions, and morbidity related to adhesions or adhesiolysis. RESULTS: Between March 2013 and December 2015, 151 patients were included. Ninety patients (59.6%) underwent open colorectal resection and 61 patients (40.4%) received laparoscopic colorectal resection. Adhesions to the incision were present in 78.9% after open and 37.7% after laparoscopic resection (P < 0.001). The incidence of abdominal wall adhesions and of any adhesion was significantly higher after open resection; the incidence of visceral adhesions did not significantly differ. The extent of abdominal wall and visceral adhesions and the median highest Zühlke score at the incision were significantly higher after open resection. There were no differences in incidence of small bowel obstruction during the interval between the colorectal and liver operations, the incidence of serious adverse events, and length of stay after liver surgery. CONCLUSION: Laparoscopic colorectal cancer resection is associated with a lower incidence, extent, and severity of adhesions to parietal surfaces. Laparoscopy does not reduce the incidence of visceral adhesions.

Quality of life, functional status and adhesiolysis during elective abdominal surgery.

BACKGROUND: Adhesiolysis during abdominal surgery can cause iatrogenic organ injury, increased operative time and a more complicated convalescence. We assessed the impact of adhesiolysis and adhesiolysis-related complications on quality of life and functional status following elective abdominal surgery. METHODS: Prospective cohort study, comparing patients requiring and not requiring adhesiolysis during an elective laparotomy or laparoscopy using the SF-36 and DASI questionnaire scores. RESULTS: 518 patients were included. Pre- and postoperative quality of life did not significantly differ between both groups. Patients with adhesiolysis had a significantly lower pre- and postoperative functional status (p < 0.01). Higher age, concomitant pulmonary disease, postoperative complications, readmissions and chronic abdominal pain 6 months after surgery were all associated with a significant and independent decline in quality of life and functional status six months after surgery. CONCLUSION: Adhesiolysis in itself does not affect functional status and quality of life six months after surgery. Postoperative complications, readmissions and chronic abdominal pain are associated with a lower health status.

A novel diagnostic aid for intra-abdominal adhesion detection in cine-MRI: pilot study and initial diagnostic impressions.

OBJECTIVE: A non-invasive diagnostic technique for abdominal adhesions is not currently available. Capture of abdominal motion due to respiration in cine-MRI has shown promise, but is difficult to interpret. This article explores the value of a complimentary diagnostic aid to facilitate the non-invasive detection of abdominal adhesions using cine-MRI. METHOD: An image processing technique was developed to quantify the amount of sliding that occurs between the organs of the abdomen and the abdominal wall in sagittal cine-MRI slices. The technique produces a "sheargram" which depicts the amount of sliding which has occurred over 1-3 respiratory cycles. A retrospective cohort of 52 patients, scanned for suspected adhesions, made 281 cine-MRI sagittal slices available for processing. The resulting sheargrams were reported by two operators and compared with expert clinical judgment of the cine-MRI scans. RESULTS: The sheargram matched clinical judgment in 84% of all sagittal slices and 93-96% of positive adhesions were identified on the sheargram. The sheargram displayed a slight skew towards sensitivity over specificity, with a high positive adhesion detection rate but at the expense of false positives. CONCLUSION: Good correlation between sheargram and absence/presence of inferred adhesions indicates quantification of sliding motion has potential to aid adhesion detection in cine-MRI. ADVANCES IN KNOWLEDGE: This is the first attempt to clinically evaluate a novel image processing technique quantifying the sliding motion of the abdominal contents against the abdominal wall. The results of this pilot study reveal its potential as a diagnostic aid for detection of abdominal adhesions.

Surgical treatment of adhesion-related chronic abdominal and pelvic pain after gynaecological and general surgery: a systematic review and meta-analysis.

BACKGROUND: Chronic pain is a frequent post-operative complication, affecting ~20-40% of patients who have undergone surgery of the female genital or alimentary tract. Chronic pain is an important risk factor for diminished quality of life after surgery. Adhesions are frequently associated with chronic post-operative pain; however, surgical treatment of adhesion-related pain is controversial. OBJECTIVE AND RATIONALE: The aim of this study was to investigate the efficacy and harms of surgical interventions for chronic post-operative pain attributable to adhesions. SEARCH METHODS: A search was conducted using PubMed, EMBASE and CENTRAL, without restrictions pertaining to date, publication status or language. Randomized trials and cohort studies from all surgical interventions for chronic post-operative pain were considered eligible. Patients with a concomitant diagnosis that could cause chronic pain (e.g. endometriosis or inflammatory conditions) were excluded. Outcome measures were graded according to clinical relevance, with improvement of pain at long-term follow-up regarded as most clinically relevant. OUTCOMES: A total of 4294 unique citations were identified, of which 13 studies met the criteria for inclusion. Two of the analysed studies were randomized trials, of which one had a low risk of bias. Only one trial, randomizing between laparoscopic adhesiolysis without an adhesion barrier and diagnostic laparoscopy, reported improvement of pain at long-term follow-up. In this trial, pain improved in 55.8% of patients after adhesiolysis and in 41.7% of patients in the control group; however, the difference was not significant (relative risk (RR) 1.34; 95% CI: 0.89-2.02). Most non-randomized studies had mid-length follow-up (6-12 months). In pooled analyses of trials and non-randomized studies, improvement of pain was reported in 72% of patients who underwent adhesiolysis (95% CI: 61-83%) at any follow-up longer than 3 months. The incidence of negative laparoscopies was 20% (95% CI: 10-30%). The overall incidence of complications following laparoscopic adhesiolysis was 4% (95% CI: 1-6%). WIDER IMPLICATIONS: Laparoscopic adhesiolysis reduces pain from adhesions in ~70% of patients in the initial phase after treatment. However, there is little evidence for long-term efficacy of adhesiolysis for chronic pain. Other drawbacks of laparoscopic adhesiolysis are the high rate of negative laparoscopies and the risk of bowel injury. At present, there is little evidence to support routine use of adhesiolysis in treatment for chronic pain. New research is needed to investigate whether the results of adhesiolysis can be improved with new techniques for diagnosis and prevention of adhesion reformation.

In-hospital costs of an admission for adhesive small bowel obstruction.

BACKGROUND: Previous research on the costs of treatment for ASBO is outdated and often based on reimbursements, rather than true healthcare provider costs of the admission and related interventions. An accurate estimate of the true costs of treatment is necessary to understand the healthcare burden and to model cost-efficacy of adhesion strategies. The aim of this study was to provide an accurate cost estimate of the in-hospital costs for treatment of adhesive small bowel obstruction (ASBO) using micro-costing methods. METHODS: Consecutive patients admitted for ASBO to the Radboud University Medical Center from November 2013 to November 2015 were included. An episode of ASBO was defined as an admission for SBO with operative confirmation of adhesions or after radiological exclusion of other causes for SBO. For the purpose of generalization we used the costs of medication and interventions as provided by the Dutch Healthcare Authority and only if these were not available local hospital costs. We evaluated costs separately for operative and non-operative treatment for ASBO. RESULTS: During the study period 39 admissions for ASBO were eligible for analysis. An operative treatment was required in 19 patients (48.7 %). Mean hospital stay for ASBO with operative treatment was 16.0 ± 11 days versus 4.0 ± 2.0 days for non-operative treatment (P = 0.003). A total of 12 patients developed complications, 2 in the non-operative group (10 %) and 10 in the operative group (52.6 %; P = 0.004). Overall costs for an admission for ASBO with operative treatment were €16 305 (SD €2 513), and for non-operative treatment € 2 277 (SD € 265) (p = <0.001). The highest expenditure with operative treatment for ASBO was made for ward stay (mean €7 856, SD €6 882), OR time (mean €2 6845, SD €1 434), ICU stay (mean €2 183, SD €4 305) and (parenteral) feeding costs (mean €1797, SD €2070). A table with correction coefficient to correct for differences in price levels for goods and services between different countries has been added. CONCLUSION: The in-hospital costs of an admission for ASBO are higher than previously thought. These costs can be used to guide hospital reimbursement policy and for the development of a cost-effective model for the use of adhesion barriers.

Risk factors for future repeat abdominal surgery.

PURPOSE: Today, 40 to 66 % of elective procedures in abdominal surgery are reoperations. Reoperations show increased operative time and risk for intraoperative and postoperative complications, mainly due to the need to perform adhesiolysis. It is important to understand which patients will require repeat surgery for optimal utilization and implementation of anti-adhesive strategies. Our aim is to assess the incidence and identify risk factors for repeat abdominal surgery. METHODS: This is the long-term follow-up of a prospective cohort study (Laparotomy or Laparoscopy and Adhesions (LAPAD) study; clinicaltrials.gov NCT01236625). Patients undergoing elective abdominal surgery were included. Primary outcome was future repeat abdominal surgery and was defined as any operation where the peritoneal cavity is reopened. Multivariable logistic regression analysis was used to identify risk factors. RESULTS: Six hundred four (88 %) out of 715 patients were included; median duration of follow-up was 46 months. One hundred sixty (27 %) patients required repeat abdominal surgery and underwent a total of 234 operations. The indication for repeat surgery was malignant disease recurrence in 49 (21 %), incisional hernia in 41 (18 %), and indications unrelated to the index surgery in 58 (25 %) operations. Older age (OR 0.98; p 0.002) and esophageal malignancy (OR 0.21; p 0.034) significantly reduced the risk of undergoing repeat abdominal surgery. Female sex (OR 1.53; p 0.046) and hepatic malignancy as indication for surgery (OR 2.08; p 0.049) significantly increased the risk of requiring repeat abdominal surgery. CONCLUSIONS: One in four patients will require repeat surgery within 4 years after elective abdominal surgery. Lower age, female sex, and hepatic malignancy are significant risk factors for requiring repeat abdominal surgery.

A Novel Diagnostic Aid for Detection of Intra-Abdominal Adhesions to the Anterior Abdominal Wall Using Dynamic Magnetic Resonance Imaging.

Introduction. Abdominal adhesions can cause serious morbidity and complicate subsequent operations. Their diagnosis is often one of exclusion due to a lack of a reliable, non-invasive diagnostic technique. Development and testing of a candidate technique are described below. Method. During respiration, smooth visceral sliding motion occurs between the abdominal contents and the walls of the abdominal cavity. We describe a technique involving image segmentation and registration to calculate shear as an analogue for visceral slide based on the tracking of structures throughout the respiratory cycle. The presence of an adhesion is attributed to a resistance to visceral slide resulting in a discernible reduction in shear. The abdominal movement due to respiration is captured in sagittal dynamic MR images. Results. Clinical images were selected for analysis, including a patient with a surgically confirmed adhesion. Discernible reduction in shear was observed at the location of the adhesion while a consistent, gradually changing shear was observed in the healthy volunteers. Conclusion. The technique and its validation show encouraging results for adhesion detection but a larger study is now required to confirm its potential.

Prior Abdominal Surgery Jeopardizes Quality of Resection in Colorectal Cancer.

BACKGROUND: Prior abdominal surgery increases complexity of abdominal operations. Effort to prevent injury during adhesiolysis might result in less extensive bowel resection in colorectal cancer surgery. The aim of this study was to evaluate the effect of prior abdominal surgery on the outcome of colorectal cancer surgery. METHODS: A nationwide prospective database of patients with primary colorectal cancer resection in The Netherlands between 2010 and 2012 was reviewed for histopathology, morbidity and mortality in patients with compared to patients without prior abdominal surgery. RESULTS: 9042 patients with and 17,679 without prior abdominal surgery were analyzed. After prior abdominal surgery 20.7 % had less than 10 lymph nodes in the histopathological specimen compared to 17.8 % without prior abdominal surgery (adjusted OR 1.17, 95 % CI 1.09-1.26). Adjusted ORs for less than 10 and 12 lymph nodes were significant in colon cancer resection and not in rectal cancer resection. Subgroups of patients who had previous hepatobiliary surgery or other abdominal surgery had a higher incidence of inadequate number of harvested lymph nodes. Prior colorectal surgery increased the percentage of positive circumferential rectal resection margin by 64 % (12.5 and 7.6 %; adjusted OR 1.70, 95 % CI 1.21-2.39). For colon cancer morbidity was significantly higher in patients with prior surgery (33.2 and 29.7 %; adjusted OR 1.18, 95 % CI 1.10-1.26), 30-day mortality was comparable (4.7 % prior surgery and 3.8 % without prior surgery; adjusted OR 1.01, 95 % CI 0.88-1.17). CONCLUSIONS: Prior abdominal surgery compromises the quality of resection and increases postoperative morbidity in patients with primary colorectal cancer.

Long-term impact of adhesions on bowel obstruction.

BACKGROUND: The incidence of reoperation for adhesive bowel obstruction after general abdominal surgery is 2.5% and carries a considerable risk of mortality and morbidity. Adhesions account for 56% of all cases of bowel obstruction. Most epidemiologic knowledge regarding adhesive bowel obstruction is derived from data of national registries and retrospective cohorts of elective abdominal surgery. Because of the design of these studies, it remains unknown whether specific operative factors impact the occurrence of bowel obstruction. We aimed to comprehensively assess risk factors for the incidence of adhesive bowel obstruction with emphasis on intraoperative surgical factors. METHODS: Follow-up study of the prospective LAPAD study (LAParotomy or LAParoscopy and Adhesions study; clinicaltrials.gov registration number: NCT01236625) that included patients undergoing all types of elective open or laparoscopic abdominal surgery. The primary endpoint of this study was (suspected) adhesive bowel obstruction. Univariable and multivariable logistic regression analysis were used to assess risk factors. RESULTS: A total of 604 (88%) of 715 patients were included; 38 (6%) patients experienced an episode of adhesive bowel obstruction. Surgery on the lower gastrointestinal tract (odds ratio 4.57, P < .01) and the severity of adhesions in the operative area (odds ratio 2.37, P = .04) independently increased the risk for adhesive small bowel obstruction. CONCLUSION: Patients undergoing surgery on the lower gastrointestinal tract and patients with more severe adhesions present at surgery have an increased risk for adhesive bowel obstruction.

Impact of Adhesiolysis on Outcome of Colorectal Surgery.

BACKGROUND/AIMS: Adhesiolysis is a frequent part of colorectal surgery, potentially impeding the operation and causing inadvertent bowel injury. Such difficulties might compromise convalescence and oncological quality of resection. The aim of this prospective cohort study was to assess the impact of adhesiolysis on clinical outcomes and histopathological results in colorectal surgery. METHODS: Colorectal procedures were selected from a prospective cohort study of adhesiolysis-related problems. We compared the incidence of bowel injury, morbidity, costs, and the histopathology between patients undergoing elective colorectal surgery with or without adhesiolysis. RESULTS: Two hundred and forty nine colorectal surgeries were analysed. Adhesiolysis was required in 59.0%. The mean adhesiolysis time was 28 min. In the adhesiolysis group, enterotomies occurred in 6.1% and seromuscular injuries in 27.2% compared to 0 and 6.9% respectively in the non-adhesiolysis group (p = 0.012 and p < 0.001). In patients requiring adhesiolysis, 29.9% had major surgery-related complications (MSRC) compared to 15.7% without adhesiolysis (p = 0.007). There were no statistically significant differences regarding inpatient costs and resection margin or number of harvested lymph nodes. CONCLUSIONS: Adhesiolysis during colorectal surgery is related to an increased incidence of iatrogenic bowel injuries and MSRC. Despite the technical challenges associated with adhesiolysis, good histopathological results were obtained in oncological resections.

Adhesiolysis in Patients Undergoing a Repeat Median Laparotomy.

BACKGROUND: Adhesiolysis during repeat surgery is associated with a high incidence of iatrogenic enterotomies and an increase in postoperative complications. Identification of risk factors would improve preoperative counseling and operating room strategy. OBJECTIVE: The aim of this study was to identify preoperative risk factors for prolonged and difficult adhesiolysis in a repeat median laparotomy. DESIGN: This is a prospective cohort study. Univariate and multivariate analyses were used to assess the risk factors for prolonged and difficult adhesiolysis. SETTINGS: This study was conducted at Radboud University Medical Center. PATIENTS: Patients participating in the LAPAD study (ClinicalTrials.gov Identifier: NCT01236625) undergoing an elective repeat median laparotomy were selected. MAIN OUTCOME MEASURES: Detailed data regarding adhesiolysis to gain entry to the abdomen and adhesions underneath the previous incision were gathered by direct observation. RESULTS: A total of 259 patients underwent a repeat median laparotomy. Adhesiolysis was required for 230 patients (89%); the remaining 29 patients (11%) did not have adhesions underneath the incision. Median adhesiolysis time underneath the midline incision was 10 minutes (interquartile range, 5-25). Seventy-six patients (29%) had grade 1 or grade 2 adhesions; 108 (42%) had grade 3; and 46 (18%) had grade 4. The number of previous laparotomies was the only independent risk factor for prolonged (p ≤ 0.01; 95% CI, 2.5-14.10) and difficult adhesiolysis (p ≤ 0.01; OR, 4.21; 95% CI, 1.74-10.17). History of peritonitis, anatomical location of previous surgery, and the time interval between consecutive median laparotomies did not prolong adhesiolysis. LIMITATIONS: This study involved retrospective data collection of patients' medical histories. No data were collected on the severity of previous peritonitis. CONCLUSIONS: This study demonstrates that 4 or more previous laparotomies and the presence or history of an intraperitoneal synthetic mesh are independently associated with a longer duration of adhesiolysis needed to gain access to the abdomen. A short time interval between median laparotomies or a history of peritonitis did not prolong the duration of adhesiolysis.

Response to pathological processes in the peritoneal cavity--sepsis, tumours, adhesions, and ascites.

The peritoneum is one of the commonest sites for pathological processes in pediatric surgery. Its response to pathological processes is characterized by an inflammatory reaction with specific pathways depending on the type of injury or peritoneal process involved. This review discusses the current understanding of peritoneal inflammation, adhesion formation, intra-abdominal sepsis, peritoneal metastasis, and ascites and briefly reviews new therapeutic strategies to treat or prevent these pathological entities. Recent studies have improved the understanding of peritoneal responses, resulting in possible new targets for prevention and therapy.

Efficacy and safety of the C-Qur™ Film Adhesion Barrier for the prevention of surgical adhesions (CLIPEUS Trial): study protocol for a randomized controlled trial.

BACKGROUND: Adhesions develop in over 90% of patients after intra-abdominal surgery. Adhesion barriers are rarely used despite the high morbidity caused by intra-abdominal adhesions. Only one of the currently available adhesion barriers has demonstrated consistent evidence for reducing adhesions in visceral surgery. This agent has limitations through poor handling characteristics because it is sticky on both sides. C-Qur™ Film is a novel thin film adhesion barrier and it is sticky on only one side, resulting in better handling characteristics. The objective of this study is to assess efficacy and safety of C-Qur™ Film to decrease the incidence of adhesions after colorectal surgery. METHODS/DESIGN: This is a prospective, investigator initiated, randomized, double-blinded, multicenter trial. Eligible patients undergoing colorectal resection requiring temporary loop ileostomy or loop/split colostomy by laparotomy or hand assisted laparoscopy will be included in the trial. Before closure, patients are randomized 1:1 to either the treatment arm (C-Qur™ Film) or control arm (no adhesion barrier). Patients will return 8 to 16 weeks post-colorectal resection for take down of their ostomy. During ostomy takedown, adhesions will be evaluated for incidence, extent, and severity. The primary outcome evaluation will be assessment of adhesions to the incision site. It is hypothesized that the use of C-Qur™ Film underneath the primary incision reduces the incidence of adhesion at the incision by 30%. To demonstrate 30% reduction in the incidence of adhesions, a sample size of 84 patients (32 + 10 per group (25% drop out)) is required (two-sided test, α = 0.05, 80% power). DISCUSSION: Results of this study add to the evidence on the use of anti-adhesive barriers in open and laparoscopic 'hand-assisted' colorectal surgery. We chose incidence of adhesions to the incision site as primary outcome measure since clinical outcomes such as small bowel obstruction, secondary infertility and adhesiolysis related complications are considered multifactorial and difficult to interpret. Incidence of adhesions at repeat surgery is believed to be the most valuable surrogate endpoint for clinically relevant adhesion prevention, since small bowel obstruction and adhesiolysis at repeat surgery are not likely to occur when complete adhesion reduction in a patient is accomplished. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01872650, registration date 6 June 2013.

Benefits and harms of adhesion barriers for abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Formation of adhesions after peritoneal surgery results in high morbidity. Barriers to prevent adhesion are seldom applied, despite their ability to reduce the severity of adhesion formation. We evaluated the benefits and harms of four adhesion barriers that have been approved for clinical use. METHODS: In this systematic review and meta-analysis, we searched PubMed, CENTRAL, and Embase for randomised clinical trials assessing use of oxidised regenerated cellulose, hyaluronate carboxymethylcellulose, icodextrin, or polyethylene glycol in abdominal surgery. Two researchers independently identified reports and extracted data. We compared use of a barrier with no barrier for nine predefined outcomes, graded for clinical relevance. The primary outcome was reoperation for adhesive small bowel obstruction. We assessed systematic error, random error, and design error with the error matrix approach. This study is registered with PROSPERO, number CRD42012003321. FINDINGS: Our search returned 1840 results, from which 28 trials (5191 patients) were included in our meta-analysis. The risks of systematic and random errors were low. No trials reported data for the effect of oxidised regenerated cellulose or polyethylene glycol on reoperations for adhesive small bowel obstruction. Oxidised regenerated cellulose reduced the incidence of adhesions (relative risk [RR] 0·51, 95% CI 0·31-0·86). Some evidence suggests that hyaluronate carboxymethylcellulose reduces the incidence of reoperations for adhesive small bowel obstruction (RR 0·49, 95% CI 0·28-0·88). For icodextrin, reoperation for adhesive small bowel obstruction did not differ significantly between groups (RR 0·33, 95% CI 0·03-3·11). No barriers were associated with an increase in serious adverse events. INTERPRETATION: Oxidised regenerated cellulose and hyaluronate carboxymethylcellulose can safely reduce clinically relevant consequences of adhesions. FUNDING: None.