Comparison of PEAK PlasmaBlade™ to Conventional Diathermy in Abdominal Based Free Flap Breast Reconstruction

Study Overview
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Brief Summary
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Electrosurgery allows for dissection with simultaneous haemostasis. One of its disadvantages is that the heat production can cause injury to the surrounding tissue which may result in wound healing problems and an increased rate of seromas. The PEAK PlasmaBlade™ (PPB) is a new electrosurgery device which may overcome this by having the ability to operate on a lower temperature, therefore reducing collateral thermal damage. Different experimental studies in both animal and human models comparing the PEAK PlasmaBlade™ and other surgical dissection devices for incisions have shown a reduction in width of zone of thermal injury, reduction in wound inflammation, increased wound strength and reduced scaring in favour of the PEAK PlasmaBlade™ and comparable to scalpel incisions. A prospective clinical study published by Dogan et al. in 2013, including 46 consecutive breast cancer patients receiving a modified radical mastectomy either with the conventional diathermy (n=22) or the PEAK PlasmaBlade™ (n=24), showed a statistically significant reduction in wound fluid production (p=0.025), leading to earlier drain removal (p=0.020) in the PEAK PlasmaBlade™ group. Comparable to oncological breast surgery, prolonged drain requirements for high wound fluid production and seromas are often experienced in the abdominal donor side after deep inferior epigastric perforator/ muscle sparing transverse rectus abdominis muscle flap (DIEP/MS-TRAM) breast reconstruction. To evaluate the effects of the PEAK PlasmaBlade™ for abdominal dissection in autologous breast reconstruction on wound fluid production and complications such a seroma, this double blinded randomised controlled clinical trial was conducted. It was hypothesised the use of the PEAK PlasmaBlade™ for the harvest of the DIEP/ MS-TRAM flap would result in 1) a shorter abdominal drains requirement (days); 2) a lower total drainage volume (mL) from the abdominal drains; 3) lower levels of inflammatory cytokines in the drain fluid and 4) less and smaller seromas would be identified using ultrasound in the follow-up period.

Detailed Description
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The study was conducted between November 2016 and May 2018 in a single centre, St. Andrew's Centre for Plastic Surgery and Burns in Broomfield Hospital, in Chelmsford United Kingdom, including all immediate and delayed DIEP/MS-TRAM patients of two senior plastic surgeons, who agreed to participate and met the in-/exclusion criteria. All participants signed an informed consent. Randomisation was performed using the Trans European Network for Clinical Trials Service (TENALEA), which is an internet-based randomisation system. Patients were either allocated to the 'Group A - diathermy' or 'Group B - PEAK PlasmaBlade™. Blinding was broken after the last patient had completed the 6-week follow-up period. All patients underwent a standardised DIEP or MS-TRAM breast reconstruction procedure. A scalpel was used to make the skin incision to the depth of the dermis. The raising of the flap was subsequently done either using the PEAK Plasma Blade™ or conventional diathermy. Before the abdominal closure two 15 French Blake drains were inserted and secured to the skin with a 2.0 Silk suture and connected to a low vacuum wound drainage system (85 kPa/neg 100mmHg). Every patient would wear an abdominal binder (9-inch, Marena) for 6 weeks post-operatively. Data on drain requirement, total daily abdominal drainage, pain, mobility and complications were collected during the inpatient stay. On day 0,1 and 2 also abdominal drain fluid was obtained. This was stored in labelled 1.5mL Eppendorf tubes in a -80°C freezer. The samples were sent to Myriad RBM, Inc. a clinical laboratory improvement amendments (CLIA) certified biomarker testing laboratory located in Austin, Texas (United States) for inflammatory cytokine analysis. Abdominal drains were removed when draining 30mL or less in 24 hours. Following discharge, patients were seen in the outpatient department after two and six weeks. At both follow-up appointments, data on complications were recorded. Also an abdominal ultrasound was performed using the V-Universal™ Stand portable ultrasound machine (SonoSite, Inc) to identify and measure abdominal seroma collections. Seromas were only aspirated if they were causing discomfort to the patient. After completion of the 6-week follow-up period patients were discharged from the study. All data were collected by the blinded principle study investigator and logged onto an electronic database. Data from an in the investigator's unit conducted pilot study on drain requirement was used to perform a power calculation.This results in a minimal sample size of 53 patients for each group (106 overall). Normal distribution was evaluated using the Shapiro-Wilk test, following this continuous data was analysed using the independent sample t-test or Mann-Whitney U Test to identify a statistically significant difference between the two groups. All right skewed was log transformed, if this resulted in a normal distribution the independent samples t-test was used to determine statistical significance. For categorical data the Pearson Chi-Square Test for numbers over 5 was used. If the count was equal to or less than 5 the Fisher's Exact Test was used to determine statistical significance. A value below or equal to 0.05 (2-tailed) was considered to be statistically significant. Linear regression (Cox proportional hazard model) was used to identify significant determinants for the time to drain removal. Variables that had a significant p-value in the univariate analysis were included in a multivariable analysis. Significant determinants could indicate confounding factors for which would be corrected. Logistic regression was used to identify determinants for complications and the presence of seroma at the 2- and 6-week abdominal ultrasound scan. Variables that had a significant p-value in the univariate analysis were included in multivariable analysis, if none of the determinates were significant p values <0.10 were included in the multivariable analysis. Significant determinants could indicate confounding factors for which would be corrected.

Official Title
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Comparison of PEAK PlasmaBlade™ to Conventional Diathermy in Abdominal Based Free Flap Breast Reconstruction - a Single Centre, Double Blinded Randomised Controlled Trial

Conditions
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Breast Reconstruction, Breast Cancer

Intervention / Treatment
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* Device: Conventional diathermy
* Device: PEAK PlasmaBlade™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults between 18-80 years, able to consent Unilateral immediate or delayed DIEP/ MS-TRAM breast reconstruction BMI >20 Exclusion Criteria: Children (<18 years) and adults older than 80 years Bilateral or bi-pedicled DIEP/MS-TRAM breast reconstruction BMI <20 Diabetic Immune-suppression Clotting disorders On steroid medication Pregnancy Active smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients randomised between having their procedure performed with one of two different electrosurgery devices
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conventional diathermy<br>DIEP/ MS-TRAM breast reconstruction free flap raise performed with conventional diathermy | Device: Conventional diathermy<br>* Abdominal free flap raise performed with conventional diathermy. Settings: cutting 40 Watt, coagulation 40 Watt.<br>|
| Experimental: PEAK PlasmaBlade™<br>DIEP/ MS-TRAM breast reconstruction free flap raise performed with PEAK PlasmaBlade™ | Device: PEAK PlasmaBlade™<br>* Abdominal free flap raise performed with PEAK PlasmaBlade™ Settings: cutting 7 (35 Watt), coagulation 7 (35 Watt)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days the abdominal drains were required | Number of days post operative | Drain requirement from the day of operation (day 0) until the day the drain was removed when producing 30ml or less/ 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flap raise time | Time required to raise abdominal flap (minutes) | Data recorded during operation | 
| Weight of abdominal flap | Weight of raised abdominal flap in grams | Data recorded during operation | 
| Inflammatory markers in abdominal drain fluid on day 0,1 and 2 | Inflammatory markers in abdominal drain fluid: TNF-alpha, IL-4, IL-6,IL-8, IL-10, IL-18, MIP-1 alpha, MIP-1 beta, MCP-1 | Drain fluid on day 0, 1 and 2 | 
| Pain score | Numerical rating scale (NRS) 0 to 10 (with 0 being no pain and 10 the worse pain imaginable) | Recorded twice a day (morning and afternoon) while an inpatient (between 3 - 14 days) | 
| Mobility | Number of steps a day | While an inpatient (between 3 - 14 days) | 
| Total abdominal drain fluid output | Total amount of fluid drained from abdominal wound (millilitres) during admission | Total amount of abdominal drain fluid collected at time of drain removal (between 3 - 14 days post-operatively) | 
| Complications | Number of complications during the study experienced by each patient (for example: Flap problems, haematoma, delayed abdominal wound healing, seroma) | In the 6-week follow-up period | 
| Interventions for complications | Number of interventions required to deal with complication for each patient (for example needle aspiration, surgery, iv antibiotics) | In the 6-week follow-up period | 
| Seroma presence on abdominal ultrasound | Abdominal ultrasound to identify | At the 2- and 6-week follow-up appointments | 
| Size of seroma collection on abdominal ultrasound | Size (length, width and depth was measured and used to estimate the size using the formula of half an ellipse) | At the 2- and 6-week follow-up appointments | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electrosurgery, Conventional diathermy, PEAK PlasmaBlade™, Deep Inferior Epigastric Perforator (DIEP) flap, Drain, Seroma