Which combination cause less inflammatory response during laparoscopic hysterectomy? Ligasure plus monopolar cautery or harmonic plus bipolar cautery?

Objective: We aimed to compare the inflammatory response with alterations in hemogram parameters, in patients who underwent laparoscopic hysterectomy and bilateral salpingo-oophorectomy for benign gynecologic conditions with ligasure plus monopolar cautery or harmonic plus conventional bipolar cautery. Methods: Patients who underwent Laparoscopic hysterectomy with bilateral salpingo-oophorectomy between January 2017 and January 2022 for benign gynecologic pathology were identified. Patients were divided into two group, according to instruments used during surgery. Instruments were used according to surgeons preference. Preoperative and postoperative in the first 24 hours hematocrit (HCT), WBC, trombocyt, neutrophil- lymphocyte (NLR), platelet-lymphocyte (PLR) ratio, mean platelet volume- lymphocyte ratio (MPVLR) and red cell distribution width- platelet ratio (RPR) values were compared. Results: During study period, a total of 462 patients underwent hysterectomy for benign gynecologic pathology. After exclusion, 212 patients were included in the study. İn the study group, 147 patients were operated with ligasure plus monopolar electrocauter and 65 with harmonic scalpel plus bipolar electrocautery. İn the postoperative period, regardless of the procedure, WBC and RPR count increase, hematocrit and trombocyt decrease in both group but the inflammatory markers lymphocyte count, neutrophyl, NLR, PLR and MPVLR count changed less in the harmonic plus bipolar cautery group which shows less inflamatuar response in this group. Conclusions: Ligasure plus monopolar cautery group compared with harmonic plus bipolar cautery group cause more inflammatory changes in complete blood count values. However, further studies are needed to show whether these changes in laboratory findings affect clinical situations.


INTRODUCTION
Hysterectomy is the second most common surgery for women after cesarean section and the abdominal removal of the uterus is the most commonly used method by surgeons. 1Hysterectomy can also be done through the vagina or as a laparoscopic or robotassisted surgery.Regardless of the type of surgery used, hysterectomy is a major surgical procedure and studies have shown that these kind of major surgical trauma promotes an immunologic dysfunction that predisposes the patient to significant morbidity.Leukocyt and neutrophil count increase after the surgery, whereas lymphocytes and thrombocytes decreased because of the effects of various hormones and cytokines. 2,3Due to the surgical stress, the blood levels of cytokines, such as interleukin-1 (IL-1), tumor necrosis factor and IL-6 increase and thereby cause an increase of acute phase reactants, including immunosuppressive acidic protein, C-reactive protein and other substances.As a result, postoperative immune suppression is commonly seen in response to surgical stress due to complex interaction of various hormones (particularly adrenal corticosteroids), cytokines, and acute phase reactants. 4aparoscopic surgery should cause less immune impairment, as it is associated with less tissue damage. 5On the other hand, during laparoscopy electrosurgical devices are commonly used for hemostasis.The Ligasure TM (Valleylab Inc., Boulder, CO, USA) vessel sealing instrument and Harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, OH, USA) are the most popular devices for vessel sealing.The Ligasure™ (LS) vessel sealing instruments use a high-current, low-voltage continuous bipolar radiofrequency energy in combination with a feedback controlled response system that automatically delivers and disrupts the power according to the impedance of the tissue between the jaws of the instruments.It fuses collagen and elastin within the vessel walls, resulting in a permanent seal that can withstand three times the normal systolic pressure and seals vessels up to 7 mm. 6But Ligasure is not suitable for colpotomy so monopolar current should be used to detach the uterus from the vagina.
The other most popular device used for laparoscopic hysterectomy is Harmonic scalpel and it produces tissue effects by converting electrical energy into vibrations at more than 20,000 cycles per second which is above the audible range.It has approval of United States food and drug administration to seal vessel up to 5 mm in diameter. 6But the disadvantage of harmonic scalpel is, it does not reliably seal large vessels, so for large pedicles like infundibulopelvic and uterine artery pedicle, bipolar energy should be used for safety.][9] This inflammatory stress is very important because energy based surgical devices used for securing vascular pedicles instead of sutures produce collateral thermal damage in neighboring tissue and cause more inflammatory stress. 10here are many ways for assessing the postoperative inflammatory response but the measurement of leukocytic changes, including neutrophil-lymphocyte (NLR), platelet-lymphocyte (PLR) ratio, mean platelet volume-lymphocyte ratio (MPVLR) and red cell distribution width-platelet ratios (RPR) are easiest and cheapest methods.White blood cell (WBC), neutrophil, platelet, and lymphocyte counts as well as NLR,PLR,MPVLR and RPR have been well studied in many diseases, such as ulcerative colitis, diabetes, various cancers, surgeries and coronary artery disease. 11,12But there is not enough information in the literature about how these values change in laparoscopic hysterectomies with salpingooophorectomy.In the current study, we aimed to compare the inflammatory response with alterations in WBC, NLR, PLR, MPVLR and RPR, in patients who underwent laparoscopic hysterectomy and bilateral salpingo-oophorectomy for benign gynecologic conditions with ligasure plus monopolar cautery or harmonic plus conventional bipolar cautery.

METHODS
This study was conducted in Tepecik Education and Research Hospital, Obstetrics and Gynecology clinic, which is a reference clinic for Egean region of Turkey.Patients who underwent Laparoscopic hysterectomy with bilateral salpingo-oophorectomy between January 2017 and January 2022 for benign gynecologic pathology were identified.The records of patients were reviewed retrospectively.Preoperative and postoperative in the first 24 hours hematocrit (HCT), WBC, trombocyt, PLR, NLR, RPR and MPVLR values were compared.

Inclusion and Exclusion Criteria:
Patients with active infection, corticosteroid use, acetylsalicylic acid, and anticoagulant use were not included in the study.Due to animal studies that have shown that oophorectomy changed the leukocyte count by altering the cytokine response we only included patients with bilateral oophorectomy. 13We excluded patients whose ovaries were not taken.
Patients were divided into two group, according to instruments used during surgery.Instruments were used according to surgeons preference.Bladder and bowel injuries, blood transfusion requirements, wound infection and hematoma, postoperative respiratory system complications were evaluated as surgical complications and excluded.Maternal venous blood samples were taken into hemogram tubes.The calibrations of the device were completed and analyzed using the Pentra DF Nexus Hematology System® (Horiba Healthcare, Japan).PLR, NLR and MPVLR were calculated by dividing platelet, neutrophil and mean platelet volume counts, respectively, by the lymphocyte count and RPR was calculated by dividing red cell distribution width by the platelet count.
The Student's t-test and the Mann-Whitney U-test were used to compare the normal and the non-normal distributed quantitative variables, respectively.The paired sample t-test was used for the preoperative and postoperative comparisons of the variables with normal distribution.The Wilcoxon signed-rank test was used for the preoperative and postoperative comparisons of the variables with non-normal distribution.Pearson's chi-square test and Fisher's exact test were used to compare the qualitative data.Statistical significance was accepted at p < 0.05.

Surgical Technique Ligasure with monopolar cautery:
All patients were administered general anesthesia and positioned in the low lithotomy position.Total laparoscopic hysterectomy was performed by using one 10 mm umbilical puncture, one 10 mm left upper puncture and two 5 mm punctures for side ports.A RUMI II uterine manipulator with a Koh colpotomy ring and vaginal pneumo occluder balloon was used for manipulating the uterus and delineating the vaginal cuff.The hysterectomy was started with the division of infundibulopelvic ligaments.The infundibulopelvic ligaments and round ligaments were secured and divided by the LigaSure system (Valleylab, Boulder, CO).The vesicouterine peritoneal fold was opened and the bladder was mobilized by blunt and sharp dissection, using Ligasure until the anterior vagina was identified.
The uterine vessels were skeletonized, sealed, and divided by the LigaSure system.The vagina was entered posteriorly first by cutting with a monopolar L-hook at the cervicovaginal junction just above the uterosacral ligament, leaving the supports of the vagina intact.The incision was continued over the colpotomy ring of the uterine manipulator and the uterus was completely detached from the vagina.The uterus was pulled out of the vagina in cases with small uteri, whereas larger uteri were morcellated vaginally.A glove with sponges was placed to maintain the pneumopritoneum, and the vaginal cuff was sutured laparoscopically with a 0-vicryl suture (Ethicon, Somerville, NJ), using a 40-mm round bodied needle.Intermittent mattress suture, taking care to take bites from the angles incorporating uterosacral ligament on both sides, was taken.The Foley catheter was removed after six hours.Harmonic with bipolar cautery: Infundibulopelvic ligaments and uterine vessels were coagulated using bipolar cautery before divided by harmonic scalpel and colpotomy was done by harmonic scalpel.All other procedures were same with ligasure group.All the cases were done by AGK, ET and AHI.

RESULTS
A total of 462 patients underwent hysterectomy for benign gynecologic pathology.After exclusion, 212 patients were included in the study.The flowchart of the study is seen in Fig. 1.In the study group, 147 patients were operated with ligasure plus monopolar electrocauter and 65 with harmonic scalpel plus bipolar electrocautery.The demographic features are shown in Table-I.There were no significant differences between the groups in terms of the demographic data.
The most common indication in the ligasure group was fibroid, whereas the most common indication in the harmonic group was ovarian cyst.Regardless of the procedure, WBC and RPR count increase, hematocrit and trombocyt decrease in both group but the difference is not statistically significant.Lymphocyt count decrease in ligasure group and increase in harmonic group.(P:0,001).Neutrophyl and NLR count increase in both group, but in the ligasure group the increase is statistical significant then harmonic group (P:0,008 and P:0,001).PLR count decrease in both group, but in the harmonic group the decrease is statistical significant then ligasure (P:0,001).MPVLR count increase in ligasure group and decrease in harmonic group (P:0,001).
In the postoperative period, the inflammatory markers lymphocyte count, neutrophyl, NLR, PLR and MPVLR count changed less in the harmonic plus bipolar cautery group which shows less inflamatuar response in this group.

DISCUSSION
Cell damage due to surgical trauma causes the release of endogenous mediators.These mediators are called damage associated molecular patterns or alarmins. 14

Alarmins are recognized by Toll like receptors expressed by dendritic cells and macrophages. Activation of Toll
Which combination cause less inflammatory response during laparoscopic hysterectomy?like receptor signaling pathway causes mobilization of large quantities of immature neutrophils from the bone marrow into circulation which causes neutrophily and leucocytosis. 15Surgical trauma is associated with an increase in the leukocytes count, but also with a decrease in the number of CD4+ and CD8+ lymphocytes.One of the mechanisms responsible for the decrease in the number of lymphocytes are disturbances in the mechanisms regulating apoptosis of these cells.Beyond these, there are a lot of changes in complete blood count parameters and derivatives after surgery.Due to the combined effects of hemodilution and accelerated platelet consumption, platelet count is decreased.The more decrease in platelet count shows more surgical trauma.
The platelet-lymphocyte ratio (PLR) is a novel inflammatory marker and recent studies show that a high PLR reflects inflammation. 16Neutrophillymphocyte ratio (NLR) is used as a marker of inflammation.A higher ratio, indicative of a hyperinflammatory situation. 17Red cell distribution width (RDW), an indicator of size variability among circulating red blood cells, has gained considerable attention as an inflammatory marker. 18,19A new index, the ratio of RDW to platelet count (RPR), has been reported to reflect the severity of inflammation. 20 higher ratio, indicative of an hyperinflammatory situation.Mean platelet volume (MPV) is an indicator of platelet activation and aggregation.MPV-lymphocyte ratio (MPVLR) have been shown to be important indicator of systemic inflammation. 21Higher MPVLR indicative of an hyperinflammatory situation.
Since laparoscopic surgery is associated with less surgical trauma than conventional surgery, it can be assumed that it also causes less trauma related inflammation .But electrosurgical devices used in laparoscopy inevitably cause varying degrees of thermal spread and more inflammation than knot tying surgery.There are a lot of electrosurgical devices used in laparoscopy.Studies have evaluated the different devices in terms of their safety, efficacy, extent of thermal injury, and versatility; however, none of the devices has been proven superior over another. 22,23In the laparoscopic hysterectomy surgical technique, the vaginal cuff should be cut with a monopolar cautery or harmonic scalpel.Because of this, generally during laparoscopic hysterectomy, Ligasure plus monopolar cautery or harmonic plus bipolar cautery combination is used.Since they are the most frequently used devices, we compare this two surgical device group in terms of inflammatory markers which is inexpensive and easy to measure.
We found that, base on the laboratory findings, the inflammatory markers change more in Ligasure plus monopolar cautery group compared with harmonic plus bipolar cautery group.Similarly, Kallol et al. showed that Ligasure produced a more sustained and greater inflammatory response at 24 hours postsurgery. 5r results also showed that Ligasure plus monopolar cautery group cause more inflammatory response but it is not possible to determine which of the Ligasure or monopolar cautery caused this difference.

Limitation:
The main limitation of our study is its retrospective nature but the reliability of our medical records minimizes this limitation.The main strength of our study is large sample size and also the homogeneity between two groups, makes our result more reliable.There are many studies in literature that compare different energy devices but to our knowledge, this is the first study that compare the impact of combination of electrosurgical devices (Ligasure plus monopolar cautery or harmonic plus bipolar cautery combination) on the inflammatory markers.

CONCLUSION
Ligasure plus monopolar cautery group compared with harmonic plus bipolar cautery group cause more inflammatory changes in complete blood count.However, further studies are needed to show whether these changes in laboratory findings affect clinical situations.

Source of funding:
None.

Table - I
: Demographic features of the study group.