Open ventral hernia repair with a composite ventral patch - final results of a multicenter prospective study

Background This study assessed clinical outcomes, including safety and recurrence, from the two-year follow-up of patients who underwent open ventral primary hernia repair with the use of the Parietex™ Composite Ventral Patch (PCO-VP). Methods A prospective single-arm, multicenter study of 126 patients undergoing open ventral hernia repair for umbilical and epigastric hernias with the PCO-VP was performed. Results One hundred twenty-six subjects (110 with umbilical hernia and 16 with epigastric hernia) with a mean hernia diameter of 1.8 cm (0.4–4.0) were treated with PCO-VP. One hundred subjects completed the two-year study. Cumulative hernia recurrence was 3.0% (3/101; 95%CI: 0.0–6.3%) within 24 months. Median Numeric Rating Scale pain scores improved from 2 [0–10] at baseline to 0 [0–3] at 1 month (P < 0.001) and remained low at 24 months 0 [0–6] (P < 0.001). 99% (102/103) of the patients were satisfied with their repair at 24 months postoperative. Conclusions The use of PCO-VP to repair primary umbilical and epigastric defects yielded a low recurrence rate, low postoperative and chronic pain, and high satisfaction ratings, confirming that PCO-VP is effective for small ventral hernia repair in the two-year term after implantation. Trial registration The study was registered publically at clinicaltrials.gov (NCT01848184 registered May 7, 2013).


Background
Although there is no consensus on the ideal technique for repairing umbilical or epigastric hernias in adults, to our knowledge only two prospective randomized trials have been conducted. The first by Arroyo et al. showed an 11% versus 1% recurrence rate after primary suture and mesh repair [1]. While the second, by Polat et al. compared 3 different techniques in umbilical hernia repairs (Prolene Hernia System, Mayo repair, and onlay repair with mesh) and demonstrated recurrence rates of 0, 11, and 0%, respectively [2]. According to Arroyo et al. and also retrospectively shown by Sanjay et al., the conclusion could be drawn that the use of mesh in these patients is mandatory, no matter the diameter of the defect [3]. Due to the technical difficulty of retrorectus and preperitoneal dissection for these small hernias, an alternative approach is to use a self expanding mesh device that can be introduced via an incision at the level of the hernia into the peritioneal cavity. Once deployed, traction on the fixation points or straps leads to a flat alignment to the abdominal wall. As a quick and elegant procedure, these devices have been embraced by many surgeons.
However, further studies on the two most frequently used mesh devices revealed several issues influencing clinical outcomes. Cases of serious complications due to severe adhesion formation as well as higher recurrence rates compared to traditional retromuscular mesh placement have been reported [4][5][6]. Thus, in addition to the design of the mesh device, adequate handling of the fatty intra-abdominal structures (both falciform ligament and umbilical folds) is mandatory to achieve best outcomes. The currently available devices for repair of small ventral hernias consist of polypropylene (PP) in combination with well known anti-adhesive barriers, as ePTFE, sepramesh technology or oxidized cellulose.
Several earlier reports also mention issues with deployment using a two-strap fixation method [4,7]. Instead, by using a four-flap fixation, flat alignment to the abdominal wall might be improved. This manuscript reports the final two-year clinical results of a prospective study of patients undergoing open ventral hernia repair with intra-peritoneal positioning of a recently developed patch for hernia repair.

Methods
As reported in the early results of this prospective multicenter cohort study, patients underwent a small primary ventral hernia repair using the Parietex™ Composite Ventral Patch (PCO-VP) (Medtronic; Trevoux, France) with a diameter of 4.6, 6.6, or 8.6 cm, depending on the size of the defect [8]. The objectives were to assess hernia recurrence at 24 months follow-up and safety. All patients ≥18 years of age planned for primary ventral hernia surgery via open approach were consented if they met eligibility criteria via a screening/baseline visit within 6 weeks of their procedure. All in-and exclusion criteria were reported previously with patients in need of emergency surgery, pregnant patients and BMI > 35 kg/m 2 being excluded. The surgical procedure applied was described in detail earlier [9]. In short, opening of the hernia sac was performed, and the fascial defect was measured. The sac was dissected out and opened and possible contents were reduced. A finger was then inserted into the defect to clear the surrounding peritoneum. The PCO-VP was then inserted into the peritoneal cavity. After introduction, the mesh is pulled up gently, to flatten the patch against the abdominal wall. To fix the mesh against the abdominal wall the 4 quadrants of the patch were fixed to the margins of the fascia defect with 4 non-resorbable sutures. Although not specifically recommended, the anterior fascia was then closed over the mesh to minimize the risks for mesh infection. For hernias < 1 cm in diameter any size of PCO-VP could be used. For hernias 1-3 cm in diameter, 6.6 and 8.6 cm PCO-VP were recommended, and for hernias > 3 cm in diameter, 8.6 cm PCO-VP was recommended. The meshes were deployed in the intraperitoneal position. If intraperitoneal positioning was difficult, preperitoneal placement was performed. Laparoscopic control was only performed in 10 patients as described earlier [8], all other patients had no laparoscopy done at the end of the procedure.
The primary endpoint was recurrence at 24 months evaluated by a physical examination and by ultrasonography in all patients (not only in case of suspicion for recurrence). The secondary endpoints were recurrence at one, six-and 12-months post-surgery. Additional outcomes included: postoperative pain measured by the Numeric Rating Scale (NRS) 0-10 in accordance with the definition in 4 categories (0 = No pain, 1-3 = minor/mild pain, 4-6 = moderate pain, 7-9 = severe pain, and 10 = worst pain); postoperative patient comfort measured by the Carolina's Comfort Scale® (CCS) to assess quality of life, as well as adverse events (AEs).

Statistics
As the recurrence rate for primary ventral hernia repair using synthetic mesh is approximately 4% (range: 0-6%) [5,[7][8][9][10], assuming a 95% confidence interval, 60 patients were needed for the evaluable population. Anticipating a 20% lost to follow-up rate a minimum of 100 patients were required as the evaluable population. Recurrence rates and complications were analyzed using time to event (Kaplan-Meier) analysis, while Student ttest or non-parametric Mann-Whitney test were used for mean comparisons between sub-groups. Proportion comparisons between sub-groups were performed using Chi-square or Fisher's exact test. All tests were performed using two-side tests with an α-level of 5%. Analyses were performed using SAS® Version 9.2 or higher (SAS Inc., Cary, NC).
This study was conducted in accordance with the Declaration of Helsinki (2008), ICH-GCP guidelines, ISO 14155-2011, institutional review board, and ethics council approval. The study was registered publically at clinicaltrials.gov (NCT01848184).
In total, 3 hernia recurrences (3.0%, n = 3/101); 95%CI: 0.0-6.3%) occurred within 2 years of repair (79 days, 197 days, and 288 days after surgery) including one patient who withdrew from the study after recurrence at 79 days. Reoperations were performed for two patients: A 33-year old female with BMI of 22.6 kg/m 2 who had received an 8.6 cm PCO-VP for a 2.2 cm umbilical hernia repair experienced a hernia recurrence 79 days after surgery. A physical exam and ultrasound confirmed the recurrence. A laparoscopic reoperation confirmed a probable missed second hernia defect cephalad to the PCO-VP. Extensive adhesiolysis from omentum and colon was necessary to identify the defect and the PCO-VP prosthesis was removed. A 15 × 19 cm piece of mesh was placed intraperitoneally. The second patient was a 54-year old male with BMI of 28.4 kg/m 2 who underwent umbilical hernia repair for a 3 cm hernia with an 8.6 cm PCO-VP. This subject experienced a hernia recurrence 197 days after surgery and eventually underwent laparoscopy demonstrating 50% cupping of the PCO-VP causing the recurrence, and an open preperitoneal repair with a 9 × 16 cm mesh was performed leaving the PCO-VP in place. The third patient with recurrence was a 69-year old female patient with a BMI of 34.7 kg/m 2 who had a recurrence at 288 days. Her 1.2 cm umbilical hernia had been repaired by preperitoneal mesh placement using a 4.6 cm PCO-VP. During the original repair, the surgeon had difficulty with the intraperitoneal dissection and the mesh was placed preperitoneally rather than intraperitoneally mainly due to the patient's obesity. Reoperation for the recurrence was not performed as it was asymptomatic.
Postoperative numeric rating scale (NRS) pain scores are depicted in Fig. 1 patients were asked to rate their satisfaction with the outcome of their procedure, the vast majority of patients responded as "completely satisfied" at all points of assessment, and 99% (102/103) of patients were satisfied with their repair at 24 months postoperative (Fig. 2). One patient responded as "unsatisfied" at his last assessment-he was the patient with hernia recurrence at 197 days.

Discussion
Until now the use of different mesh devices has led to unacceptable morbidity, including gastrointestinal obstructions, mesh erosions, as well as high recurrence rates compared to other types of repair. In the present study more than 100 patients with umbilical hernia and epigastric hernia repair using the PCO-VP were investigated over the course of 2 years. Historically, these types of hernias, with relatively small defect diameters between 0.5 cm and 3 cm, have been primarily repaired using either suture closures, or the Mayo technique, yielding recurrence rates of 10-30% [10,11]. As evident from this and similar studies, the use of a prosthetic mesh significantly reduces the mid-term 2 year rates of hernia recurrence even for small defects [1,12,13]. Recurrence rates of up to 2.2% (range, 1-2.2%) have previously been demonstrated using the mesh repair [1,13] and similarly our study yielded a cumulative hernia recurrence rate of 3.0% within 24 months. With PCO-VP, the most common AEs reported were pain between discharge and 1-month follow-up (n = 27, 21.4%), and superficial wound dehiscence (n = 5, 4.0%). Pre-existing risk factors did not predispose subjects to AEs, although obesity might complicate mesh introduction in the intraperitoneal position as observed in 1 patient, which was later complicated by a recurrence. The cupping phenomenon or "potato-chip" deformities are well-known issues after the use of mesh devices for small ventral hernia repair. These complications are probably due to excessive traction on the straps in order to align the patch flatly against the parietal peritoneum [4,7]. Although mesh misalignment may also have occurred in this series [8], as laparoscopic evaluation is the only way to verify this, the low recurrence (3%) and reoperation rate observed at the end of the 2 year follow up, show that at least the clinical impact of misalignment has been minimal. Nevertheless, accurate surgical technique with complete dissection of the falciform ligament cranially and the umbilical folds caudally is mandatory to obtain best patient outcomes, especially when using the largest 8.6 cm patch. Garcia-Moreno et al. specifically examined the prothetic design of PCO-VP, in which the authors concluded, that both the intraperitoneal positioning and the incorporation of the mesh in the abdominal wall were very reliable using the four flap handles and fixation [14]. The well-known antiadhesive properties of its collagen barrier to intraperitoneal adhesions have already proven its efficacy [15][16][17].
Our observed recurrence rate of 3.0% is lower than that previously reported with other mesh devices (up to 14.8% in 25 months [4,13,[18][19][20][21], up to 12% at 16 months follow-up [22][23][24][25][26], or up to 10% after 43 months according to the regional cohort study from the Danish Hernia Database [27]). It is remarkable that a follow-up of 2 years in our studied patients did not increase the number of recurrences, despite a final ultrasound evaluation in all patients. However, it should be noted that this study does not exclude the possibility of later recurrences and that the actual recurrence rate might be slightly higher due to the number of lost to follow-up  patients. In this respect, a randomized controlled trial comparing 2 different mesh devices could reinforce the value of these results.
As reported previously, the early wound morbidity was low (4.0% incidence of superficial wound dehiscence) without any evidence of mesh infection. But, as the study is limited by the absence of a control group, no further additional conclusions about the PCO-VP compared to alternate devices or surgical mesh repair techniques can be drawn. PCO-VP provides a potentially better outcome than reported by Bontinck et al., who reported 3% (3/96) of their patients had moderate or severe pain 12 months postoperative [23]; this difference might possibly be explained by their recurrence rate and less inflammatory and foreign body reaction after implantation of the PCO-VP [14]. In our study the excellent patient outcome is reflected in the quality of life global CCS score, which incorporates the sensation, pain and movement scores.

Conclusion
The use of PCO-VP for the repair of primary umbilical and epigastric defects yielded a low recurrence rate, low postoperative and chronic pain, and high satisfaction ratings, confirming that PCO-VP is effective for small ventral hernia repair in the two-year term after implantation.