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Department of Gynecologic Surgery, CHU Estaing, 1 place Lucie Aubrac, 63058 Clermont-Ferrand Cedex 1, FranceCICE (Centre International de Chirurgie Endoscopique), Faculty of Medicine, Clermont-Ferrand, France1
Department of Gynecologic Surgery, CHU Estaing, 1 place Lucie Aubrac, 63058 Clermont-Ferrand Cedex 1, FranceCICE (Centre International de Chirurgie Endoscopique), Faculty of Medicine, Clermont-Ferrand, France1
Department of Gynecology and Obstetrics, Rouen University Hospital, FranceResearch Group 4308, Spermatogenesis and Gamete Quality, IHU Rouen Normandy, IFRMP23, Reproductive Biology Laboratory, Rouen University Hospital, 1 Rue de Germont, 76000 Rouen, France
Department of Gynecologic Surgery, CHU Estaing, 1 place Lucie Aubrac, 63058 Clermont-Ferrand Cedex 1, FranceCICE (Centre International de Chirurgie Endoscopique), Faculty of Medicine, Clermont-Ferrand, France1
To compare the most used types of surgical techniques, for peritoneal lesions management, to Plasmajet® (PJ), in term of healing and post-operative adhesion.
Study design
Prospective, experimental animal study. Female pigs (Landrace/Large White-Pietran) weighing 20–25 kgs were used for the experiments. Eleven areas of 2 cm2 were treated on each lateral side of the peritoneal wall. Two areas of control, 2 of surgical resection with scissors, 2 of bipolar coagulation, 2 of Plasmajet® 10 low (PJ10L, adjustment of the Plasmajet®) used in contact with the peritoneum, 2 of PJ10L used at 3–5 mm from the peritoneum, 2 of PJ10L used at 10 mm, 2 of PJ used at 10 High (PJ10H) close to the peritoneum, 2 of PJ10H used at 3–5 mm, 2 of PJ10H used at 10 mm, 2 of PJ used at 40 Low (PJ40L) used at 3–5 mm, 2 of PJ40L used at 10 mm from the peritoneum.
Results
For each 2 areas, one was removed immediately for histological analysis. All animals were reoperated 14 days later to evaluate macroscopic healing, adhesion score, histological inflammation and mesothelialization. Immediate histological analysis shows that in every treated area the peritoneum was completely vaporized, coagulated or removed. After resection, the healing was macroscopically perfect and there was no adhesion, as in the control area. After bipolar coagulation in half of cases there was adhesion. There was no adhesion after treatment by Plasmajet® 10 low used at 10 mm from the peritoneum.
Conclusion
Surgical resection leads to perfect healing, and no adhesion formation. The use of Plasmajet® 10 low used at 10 mm from the peritoneum could be an alternative to resection, because it allows complete superficial destruction, with a low rate of adhesion. Further study is required to explore and assess fully the potential of this device.
Many surgical techniques exist to treat endometriosis lesions: the most frequently used are resection and bipolar coagulation, but laser or argon plasma ablation (Plasmajet®) can also be used. There are no scientific arguments to use a type of resection or destruction for peritoneal endometriosis compared to another. The principles of action of these methods are very different, and the influence of each method on the quality of treatment or on wound healing and adhesion formation is not yet known. The PlasmaJet® System (PlasmaSurgical, Inc. Roswell, Georgia, USA) is a surgical technology designed to facilitate cutting, coagulation and ablation of tissue. The PlasmaJet® uses a low DC voltage (direct current voltage) applied between internal bipolar electrodes to produce highly energetic electrically neutral pure argon plasma. The plasma can be used in three forms: light to illuminate the surgical field, heat to coagulate bleeding surfaces, and kinetic energy to vaporize or cut tissue. This easy-to-use device is utilized for a wide variety of surgical procedures including gynecology. The energy from the PlasmaJet® seems to be short-lived, hence tissue effects are superficial with minimal lateral spread [
]: the average depth and width of tissue damage with the application of the Plasmajet® coagulator for 5 s at a low power of 20% is 0.62 and 4.24 mm, respectively. It therefore appears to be a safe method of coagulation on gynecological tissues. This implies an ideal safe source of energy for dealing with superficial endometriosis lesions, with minimal effect on underlying tissue [
]. In this study, we compared the most frequently-used surgical techniques for peritoneal lesions (i.e. surgical resection with scissors and bipolar coagulation) to PlasmaJet® vaporization. We compared all techniques in terms of wound healing, post-operative adhesion, inflammation, and mesothelialization, and we also compared the effects of the Plasmajet® at different power settings and at different distances (tip to tissue) from the peritoneum.
Postsurgical adhesions have four major negative impacts on health care outcomes. First, adhesions are the major cause of small bowel obstruction and a leading cause of infertility and chronic pelvic pain in women [
]. Second, adhesions are associated with multiple surgical complications. Third, these complications lead to a greater surgical workload and utilization of hospital and other health care resources. Fourth, all these negative impacts result in a significant economic burden to society [
]. The economics of adhesions is another way of approaching this problem. The annual cost of adhesion-related problems in Sweden was estimated as 39.9–59.5 million [
]. Consequently the importance of identifying a surgical technique that may reduce this burden would appear crucial for healthcare providers.
Animals and methods
Animals
Pigs (Landrace/Large White-Pietran) weighing 20–25 kg were used for the experiment. Institutional Review Board approval was obtained prior to starting the study and all investigations complied with the National Institutes of Health Guide for the Care and Use of Laboratory Animals [
] (U.S. Department of Health and Human Services, Public Health Service, 1985). Standard swine feed and purified water were provided ad libitum and then pigs were deprived of food 24 h before surgery.
Anesthesia
Anesthesia was induced with an intramuscular administration of 2 ml of Stresnil (Janssen-Cilag, Berchem, Belgium) and 3 ml of Zoletil100 (Virbac, Glattbrugg, Switzerland). Pigs were intubated and mechanically ventilated (Aeroporc®, Clermont-Ferrand, France). Anesthesia was maintained with intravenous Propofol (5 ml/10 kg).
Surgical procedures
The animals were placed in the supine position and immobilized, a CO2 pneumoperitoneum was created. Three operative trocars were introduced on the midline. Eleven zones of 2 cm2 were treated laterally on each side of the peritoneal wall, each neighboring zone separated from the other by 5 mm (Fig. 1). We performed a pilot study on one animal to test the different Plasmajet® settings, and the distribution of the treatment zones (data not reported). It appeared that in the areas treated with the Plasmajet® set at 40 low and used in contact with the peritoneum the injuries on the underlying tissue were too great, so this setting was excluded (Fig. 2).
For each type of treatment zone, one was removed immediately (left side) for histological analysis to assess destruction. All animals were euthanized 14 days later. After euthanasia the 11 zones on the right wall were easily identified and each zone was well separated from the others (Fig. 1). The 11 zones were harvested to evaluate macroscopic healing and adhesion formation (score), and to conduct a histological analysis to assess inflammation and mesothelialization.
Macroscopic results: adhesion and healing
The extent, type and severity of any adhesions were evaluated. We took pictures of each zone, and the pictures were then evaluated by a single blinded observer. The extent of adhesions was assessed by estimating the overall length of the treated zone covered by adhesive tissue and scored according to Vrijland et al. [
Effects of supplemental perioperative oxygen on post-operative abdominal wound adhesions in a mouse laparotomy model with controlled respiratory support*.
], from 1/”filmy adhesion, easy to separate by blunt dissection” to 4/“Very strong adhesion; lysis possible by sharp dissection only; organs strongly attached with severe adhesions; damage of organs hardly preventable”. Severity of adhesion formation was calculated by multiplying the extent and the type of adhesions for each location [
Specimens for histological analysis (11 left zones) were transported to the laboratory on the day of the first operation (Post-operative Day 0–POD0). Histological assessment of peritoneal destruction was performed at POD0 using the Periodic acid–Schiff staining method. All slides were reviewed by a single blinded pathologist. At post-operative day 14 (POD14), following laparotomy, we removed the 11 zones on the right side for histological analysis. Specimens were transported in formalin to the laboratory then embedded in paraffin, and then manually sectioned with a microtome to obtain paraffin sections. For each treated zone we studied 3 different histological regions in order to average our measurement.
Our aim was to evaluate acute inflammation (polymorphonuclear leukocytes per high-powered field (HPF)), and mesothelialization (%) [
]. The mesothelialization score is evaluated with the mesothelial layer growth (%) on the specimens surface. The inflammation score (×40 magnification) was defined as the mean inflammation score of the three regions studied. The mesothelialization score (×20 magnification) was defined as the mean mesothelialization score of the three regions.
Statistical analysis
Statistical analysis was performed using Stata software, version 13 (StataCorp, College Station, TX, U.S.). The tests were two-sided, with a type I error set at α = 0.05. Continuous data were presented as the mean ± standard deviation or the median [interquartile range] according to statistical distribution (assumption of normality checked using normal probability plots and Shapiro-Wilk’s test). To take into account between and within subject variability (due to several measurements for a given animal), ANOVA for repeated measures or the non-parametric Friedman test (if conditions for ANOVA were not met) followed by the appropriate post-hoc test (Tukey-Kramer) were performed to examine differences in the mean inflammation score, mesothelialization score, adherences and macrohealing of tissue damage when treated with resection, bipolar coagulation and different power levels and distances using the Plasmajet®. When appropriate, these analyses were completed by random-effects models considering the variable associated to animal as a random effect.
Results
There were no unplanned complications, morbidities or mortalities. All animals survived the study period and recovered from surgery with no complications. No animals showed signs of peritonitis postoperatively before euthanasia. This clinical impression was confirmed during laparotomy at POD 14 for all six animals (no abscess nor signs of intraperitoneal infection).
Macroscopic healing scores were significantly different between the control zone and all the various techniques except for resection. In the resection group, healing was perfect and identical to the control group. It was significantly better than in the other groups (score 1 for resection vs 2.77 for Plasmajet® and bipolar coagulation). There was no significant difference in macroscopic healing between high or low mode PlasmaJet® when the distance from peritoneal tissue was constant (0, 3–5 mm, or 10 mm) .
Table 1Results for macroscopic healing, adhesion formation and severity, average score of inflammation and mesothelialization.
However, between all types of Plasmajet® power settings and application distances, PJ10L10 had a better healing score (score 2 for PJ10L10 vs 2.76 for other PJ types), even if this score was not as good as the resection score. No adhesion formation was found with resection, PJ10L10 and the control group. The use of PJ10H10 seemed to cause the most severe adhesion formation (66%), but the adhesion formation and severity score weren’t significantly different between the control zone and all the various techniques. However, there was a significant difference between PJ10L10 on the one hand and all other Plasmajet® settings and bipolar coagulation on the other hand: PJ10L10 caused significantly fewer adhesions (0% vs 43.75%). There was also a significant difference in terms of adhesion severity between the same two groups (0 vs 2.98). Resection seemed to cause less adhesion also, and the difference was statistically significant between resection and the group including bipolar coagulation and all Plasmajet® settings except PJ10L10 (0% vs 43.75%), but it became non-significant (0% vs 38.8) when PJ10L10 was included in the compared group.
Histological findings
A total of 66 histological regions were studied to assess destruction at POD0 (6 pigs × 11 left zones), and 189 to assess inflammation and mesothelialization at POD14 (6 pigs × 11 right zones × 3 regions). Histological analysis showed that in every treated zone the peritoneum was completely destroyed or coagulated whatever the type of surgical technique or the Plasmajet® level of energy used (Fig. 4). Use of the Plasmajet® at a power setting of 40 caused a mesothelialization score in excess of 3.50 (average histologic grading scale 3.67, >75%) while use of the Plasmajet® at a power setting of 10High and a distance of 3–5 mm from the peritoneum was the only technique resulting in less than 50% mesothelialization (average histologic grading scale 2.06) (Fig. 5). Statistically there was no significant difference between any of the groups in terms of inflammation or mesothelialization.
Fig. 4Histological analysis at POD0, for Plasmajet at different distances.
Conventional electrosurgery using high frequency current used to coagulate tissues and obtain homeostasis is recognized to cause deep tissue effects with lateral heat spread. Argon plasma energy removes the risk of arcing, alternate side burns, lateral heat effects [
]. The Plasmajet® System is an innovative technique which allows precise application of the energy to the targeted tissue while avoiding surface straying of the electrical current and accidental impact to remote zones in the surgical field. It seems to reduce instrument exchanges during surgery, hence reducing operating time and the risk of inadvertent visceral injury due to its continuously cooled tip [
]. In our study, we evaluated the impact of the Plasmajet® used at different settings and different distances on adhesion formation. At POD14, our results were very heterogeneous from one group to another, but there was a difference between the Plasmajet® used at a power setting of 10 and a distance of 10 mm from the peritoneum and all others types of Plasmajet® settings and bipolar coagulation. Finally macroscopic healing assessment showed that resection was the best technique to achieve perfect healing. The Plasmajet® system could be used as an alternative to resection in terms of healing. In our study, histological analysis showed no significant difference between inflammation/mesothelialization scores in any of the techniques compared to the control group. These results show the importance of the intraperitoneal environment, and are probably due to the fact that adhesions are covered by mesothelial cells too (Fig. 5). Postoperative adhesion formation results from a series of local events at the trauma site. Peritoneal injury by surgery, infection or irritation initiates a local inflammatory reaction, exudation, and fibrin deposition into which white blood cells, macrophages, fibroblasts, and mesothelial cells could migrate, proliferate, and/or differentiate [
]. The local interplay between inflammatory cells, macrophages and cytokines is not well understood. These events at the trauma site are modulated by factors arising from the peritoneal cavity [
]. Overall in our work there is no link between adhesion, healing, and inflammation, nor even a significant trend.
Of all the different PJ levels of power and application distances, PJ10L10 seemed to induce fewer adhesions. Conversely, stronger settings and shorter distances seemed to induce more adhesions. A distance of 10 mm tip-to-tissue seems to be the best for surgery using the Plasmajet® for vaporization of soft tissue. This distance is commonly used in other studies [
]. In our experience, in laparoscopic surgery we used the laparoscopic grasping forceps as a baseline measurement to ensure the same distance at all times. The power and distance used in daily surgery in our experience are Plasmajet® 10 low, used at 10 mm from the peritoneum.
Our comparative study aims also to assess histological outcomes immediately after treating the peritoneum. Histological analysis at POD0 showed that every zone of the peritoneum treated was completely destroyed or coagulated whatever the type of surgical technique or the level of energy used for the Plasmajet®.
The Plasmajet® appears to be a safe method for in vitro and in vivo coagulation of gynecological tissues at a power level of 20 [
]. Another possible application of the Plasmajet® technique is removing carcinomas. This technology could facilitate diaphragmatic peritoneal stripping as well as dissection of tissue close to the bowel and major vessels [
]. In oncological surgery, the Plasmajet® can also be used in vulvar cancer, to seal the lymph vessels and channels. In their study, Tanner et al. also found that the Plasmajet® effectively ablate bowel serosa in a porcine model [
]. It seems to result in a predictable tissue effect with low inflammatory response, especially when used at low power settings. These characteristics are appealing for ablation of bowel serosa implants during ovarian cancer surgery [
Although ours is an animal study with a limited number of cases, the Plasmajet® appears to possess characteristics that make it a safe and useful tool for the treatment of gynecological pathologies, especially endometriosis. Larger studies with more patients considering long-term outcomes will be needed to confirm these initial findings.
There are limitations in our study: we didn’t do immunohistochemical analysis. Another limitation is the small size of the specimens analysed, which may impact on the generalisability of findings. The immediate resection of the left side treated zones could also have modified the local peritoneal environment, and could have modified the analysis of the controlateral side. However, if there have been changes they are the same for all animals and all zones treated.
Conclusion
After surgical resection of peritoneum in a porcine model, macroscopic healing is perfect and there are no adhesions at POD14 but this technique can be difficult, risky and time consuming, especially in case of endometriosis. Use of the Plasmajet® at 10 (power level) and at 10 mm from the peritoneum could be a good alternative to surgical resection for superficial lesions, because it allows complete superficial destruction with minimal adhesion formation compared to bipolar energy and other Plasmajet® settings. Further study is required to explore and assess fully the potential of this device and whether it can replace conventional surgical techniques.
Acknowledgements
We are grateful to all staff in the Centre International de la Chirurgie Endoscopique (Clermont-Ferrand, France). We are indebted to Karl Storz Endoscopy for providing laparoscopic equipment.
All authors have made a substantial contribution to the information or material submitted for publication: N Bourdel: Principal author, design the study, P Chauvet: Second author who also collect the information, Horace Roman: third author who also collect the information.
Bruno Pereira: the statistician, Oana Tartan and Pierre Dechelotte did all the histological analysis, Michel Canis: referent for gynecological surgery and endometriosis in our center, revise the manuscript critically for content. All authors have read and approved the final manuscript.
We report financial support to pay for the animals, but no remuneration for any authors.
Dr. Bourdel reports support for travel expenses for participating in a symposium presenting the effect of the PlasmaJet.
Dr. Roman reports personal fees for participating in a symposium and a masterclass presenting his experience in the use of the PlasmaJet.
Drs. Chauvet, Pereira, Somcutian, Dechelotte and Canis have no conflicts of interest nor financial ties to disclose.
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Effects of supplemental perioperative oxygen on post-operative abdominal wound adhesions in a mouse laparotomy model with controlled respiratory support*.
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