Ultrasonic incisions produce less inflammatory mediator response during early healing than electrosurgical incisions.

As the use of laparoscopic surgery has become more widespread in recent years, the need has increased for minimally-invasive surgical devices that effectively cut and coagulate tissue with reduced tissue trauma. Although electrosurgery (ES) has been used for many generations, newly-developed ultrasonic devices (HARMONIC? Blade, HB) have been shown at a macroscopic level to offer better coagulation with less thermally-induced tissue damage. We sought to understand the differences between ES and HB at a microscopic level by comparing mRNA transcript and protein responses at the 3-day timepoint to incisions made by the devices in subcutaneous fat tissue in a porcine model. Samples were also assessed via histological examination. ES-incised tissue had more than twice as many differentially-expressed genes as HB (2,548 vs 1,264 respectively), and more differentially-expressed proteins (508 vs 432) compared to control (untreated) tissue. Evaluation of molecular functions using Gene Ontology showed that gene expression changes for the energized devices reflected the start of wound healing, including immune response and inflammation, while protein expression showed a slightly earlier stage, with some remnants of hemostasis. For both transcripts and proteins, ES exhibited a greater response than HB, especially in inflammatory mediators. These findings were in qualitative agreement with histological results. This study has shown that transcriptomics and proteomics can monitor the wound healing response following surgery and can differentiate between surgical devices. In agreement with clinical observations, electrosurgery was shown to incur a greater inflammatory immune response than an ultrasonic device during initial iatrogenic wound healing

Comparison of the overall effect of the identified gene expression changes in response to harmonic blade and electrosurgery incisions on biological processes of relevance to wound healing using GOModeler workflow.

<p>We used Gene Ontology terms to represent specific biological processes, and identify the known effect on a function under consideration such as ‘positively regulates’ or ‘negatively regulates’. The magnitude of the changes in gene expression was also taken into account.</p

Up-regulated genes in response to Electrosurgery and Harmonic incisions.

<p>Up-regulated genes in response to Electrosurgery and Harmonic incisions.</p

Histopathology analysis revealed mild degeneration/necrosis of the adipose and/or connective tissue (black arrows), mild acute inflammation (yellow arrows), mild fibrin infiltration (blue arrow) and minimal hemorrhage (red arrow) are noted within the connective tissue/fat immediately surrounding the incision by electrosurgery.

<p>The images were acquired at 50X magnification after hematoxylin and eosin staining.</p

Proteins with significant changes in expression in response to electrosurgery and harmonic blade incisions.

<p>*Genbank or Uniprot accessions.</p

Summary of the biological processes as described by Gene Ontology, represented in the differentially expressed proteins in response to harmonic blade and electrosurgery incisions.

<p>Summary of the biological processes as described by Gene Ontology, represented in the differentially expressed proteins in response to harmonic blade and electrosurgery incisions.</p

Summary of the biological processes as described by Gene Ontology, represented in the differentially expressed genes in response to harmonic blade and electrosurgery incisions.

<p>Summary of the biological processes as described by Gene Ontology, represented in the differentially expressed genes in response to harmonic blade and electrosurgery incisions.</p

Comparison of the overall effect of the identified protein expression changes in response to harmonic blade and electrosurgery incisions on biological processes of relevance to wound healing using GOModeler workflow.

<p>We used Gene Ontology terms to represent specific biological processes, and identify the known effect on a function under consideration such as ‘positively regulates’ or ‘negatively regulates’.</p

Proteins with significant changes in expression in response to either electrosurgery or harmonic blade incisions.

*<p>Genbank or Uniprot accessions.</p>#<p>n.s. indicates that there was no significant change in protein expression.</p>$<p>n.d. indicates that the protein was not identified in the dataset.</p