+ MODEL Asian Journal of Surgery (2017) xx, 1e7 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.e-asianjournalsurgery.com ORIGINAL ARTICLE Is the superior laryngeal nerve really safe when using harmonic focus in total thyroidectomy? A prospective randomized study Kemal Arslan a,*, Bulent Erenoglu a, Osman Dogru a, Gultekin Ovet b, Ersin Turan a, Arif Atay a, Hande Koksal a Department of General Surgery, Saglık Bilimleri University, Konya Training and Research Hospital, Turkey b Department of Otorhinolaryngology, Konya Training and Research Hospital, Konya, Turkey a Received 23 August 2016; received in revised form 18 November 2016; accepted 15 December 2016 KEYWORDS harmonic focus; superior laryngeal nerve; thyroidectomy Summary Background: Harmonic focus (HF) was introduced in thyroid surgery in an effort to reduce operation time and complications Objective: The present study aimed to compare function of superior laryngeal nerve and incidence of other postoperative complications in total thyroidectomies using HF and conventional ligation (CL) Methods: The trial is a randomized single-center, single-blinded study Patients aged ! 18 years scheduled for total thyroidectomy were considered for participation An ultrasonic dissector was used for coagulation and cutting in the HF group, while the standard technique was used in the CL group Demographic, surgical data, and complications were recorded Data were analyzed using SPSS for Windows Results: Of 244 eligible patients, data of 206 patients who completed the study were analyzed The groups were similar in terms of age, sex, and indication for operation The mean operative time in the HF group was significantly shorter than that in CL group (p Z 0.01) Drain necessity, duration of drainage, duration of postoperative hospitalization, and the incidence of postoperative complications was similar in the groups (p > 0.05) The external branch of the superior laryngeal nerve and recurrent laryngeal nerve palsy were noted in three and two patients in the HF group and in two and one patients in the CL group at months Conclusion: To the best of our knowledge, this is the first study comparing conventional technique with HF in total thyroidectomy, focusing on the function of the external branch of the * Corresponding author Department of General Surgery, Saglık Bilimleri University, Konya Training and Research Hospital, Hacı S‚aban Mah, No 197, PK 42090, Meram, Konya, Turkey E-mail address: arslanka74@hotmail.com (K Arslan) http://dx.doi.org/10.1016/j.asjsur.2016.12.004 1015-9584/ª 2017 Asian Surgical Association and Taiwan Robotic Surgical Association Publishing services by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic focus in total thyroidectomy? A prospective randomized study, Asian Journal of Surgery (2017), http://dx.doi.org/10.1016/j.asjsur.2016.12.004 + MODEL K Arslan et al superior laryngeal nerve using laryngostroboscopy; results showed that HF is as safe as the conventional technique ª 2017 Asian Surgical Association and Taiwan Robotic Surgical Association Publishing services by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) Introduction Thyroidectomy is the most common surgical procedure in general surgery departments and total thyroidectomy is performed in the majority of thyroid diseases The thyroid gland is highly vascularized, and is closely related to vital anatomic structures such as parathyroid glands, recurrent laryngeal nerve (RLN), and superior laryngeal nerve (SLN) Therefore, meticulous hemostasis should be provided to avoid bleeding, provide a clear view of the surgical field, and prevent injury to the vital structures The most common technique continues to be practiced in thyroidectomy is the conventional “clamp and tie” technique After the introduction of the harmonic scalpel (HS) in the 1990s, an innovative technical improvement of the device for thyroid surgery, harmonic focus (HF) shears, was implemented in 2008.1 Harmonic devices use ultrasound energy to cut and coagulate soft tissue and vessels at much lower temperatures than radiofrequency-based devices, with minimal thermal damage to the surrounding tissue.1 In the literature, a meta-analyses comparing HS and conventional technique reported shorter operation time, hospital stay, less bleeding, and lower rates of hypocalcemia with HS than with the conventional technique.2,3 The meta-analyses comparing HF with other techniques also revealed a shorter operative time and hospital stay, lower drainage volume and blood loss, lower rates of transient hypocalcemia, but similar rates of permanent hypocalcemia and RLN palsy.4 However, most studies did not emphasize whether the external branch of the SLN (EBSLN) is safe in total thyroidectomy The primary aim of the present study was to assess and compare the function of SLN by laryngostroboscopy in patients undergoing total thyroidectomy using HF and conventional ligation (CL), and the secondary aim was to assess and compare the incidence of other postoperative complications in the two treatment groups Methods 2.1 Study design and patient selection The trial was designed as a randomized single-center, single-blind study The protocol was approved by the Regional Ethics Committee of Necmettin Erbakan University, Konya Turkey (Number 2011/80) The study protocol was registered at www.clinical.trials.gov (NCT00306839) All patients aged ! 18 years scheduled for total thyroidectomy in the Department of Surgery of Konya Education and Research Hospital from January 2013 to February 2015, were considered for participation in the trial Patients with a history of previous thyroid surgery, radiation therapy to the neck, those scheduled for hemithyroidectomy or requiring cervical lymph node dissection, and those with calcium metabolism disorders or hoarseness were excluded All patients underwent preoperative and postoperative video laryngostroboscopy by an experienced otorhinolaryngologist Vocal fold mobility and bowing, regularity and symmetry of the mucosal wave, and degree of glottic closure were evaluated, and the patients with SLN and/or RLN paralysis were also excluded Patients were thoroughly informed about both surgical procedures and they agreed to be blinded to the surgical method during the study period Selection of eligible patients began on January 2013 and the study was completed in February 2015 Using a computer-generated random sequence and block randomization, 230 patients were randomly allocated to HF or CL groups in a blinded fashion (Figure 1) The allocations were concealed in sealed opaque envelopes, and were enclosed in the patient files The envelopes were opened in the operating room and the surgeon performed the type of surgery written in the envelope All patients underwent surgery by or under the supervision of two surgeons (O.D and K.A.) Total thyroidectomy was performed with the same technique in all patients After Kocher collar incision, skin-platysma flaps were created, and then the strap muscles were separated in the midline to expose the thyroid gland The gland was rotated medially and the middle thyroid vein was identified and ligated The superior thyroid vessels were isolated and divided individually as close to the thyroid gland as possible in order to avoid damage to the SLN The thyroid lobe was retracted medially and anteriorly At this step, identification of the RLN is obligatory before completing the division of the branches of the inferior thyroid artery Attention was directed towards the visualization of the inferior and superior parathyroid glands In almost all cases, RLNs and parathyroid glands were identified If ischemia was suspected, autotransplantation of the parathyroid glands into the sternocleidomastoid muscle was performed In the HF group, ultrasonic dissector was used for hemostasis, and HF (Ethicon Endo surgery, Cincinnati, OH, USA) was used for coagulation and cutting In the CL group, surgery was performed using the standard surgical technique and vicryl 3-0/4-0 stitches were used to achieve hemostasis In all patients in both groups, the recurrent laryngeal nerves were identified and preserved bilaterally The superior pole vessels were individually identified, skeletonized ligated and divided by using HF low on the thyroid gland to avoid injury to the external branch of the superior laryngeal nerve (Figures 2e5) Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic focus in total thyroidectomy? A prospective randomized study, Asian Journal of Surgery (2017), http://dx.doi.org/10.1016/j.asjsur.2016.12.004 + MODEL Harmonic focus in total thyroidectomy Figure Treatment of flow chart No funding or financial support was received from the manufacturer of the harmonic devices Patients who were lost to follow-up during the study were excluded and only patients who completed the study were included in the analysis to the end of wound closure), length of hospital stay, need and duration of drainage and complications (bleeding within 24 hours of operation that necessitated reoperation, RLN palsy, EBSLN palsy), late hematomas (developing > 24 2.2 Data collection Patient demographic and surgical data, including the surgical technique, duration of surgery (time from skin incision Figure Identification recurrent laryngeal nerve Figure Dissection of inferior thyroid artery Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic focus in total thyroidectomy? A prospective randomized study, Asian Journal of Surgery (2017), http://dx.doi.org/10.1016/j.asjsur.2016.12.004 + MODEL K Arslan et al Figure Dissection of superior thyroid artery hours after operation), were obtained from medical files and operating notes If the surgical field was not completely dry, a suction drain was inserted at the end of surgery The amount of drainage was measured every morning and the drain was removed whenever 0.05) Similarly, no difference was found in the duration of drainage (1.02 Ỉ 0.14 vs 1.05 Ỉ 0.23 day) and the mean duration of postoperative hospitalization (1.39 Ỉ 0.56 vs 1.32 Ỉ 0.54 days) No mortality was observed and none of the patients developed wound infection or wound dehiscence The most frequent postoperative complications were temporary hypocalcemia (n Z 27) and seroma formation (n Z 25) Early postoperative bleeding requiring reoperation was only noted in two patients (2%) in the CL group The rates of seroma and hematoma were higher in the CL group (13.9% and 6.9%) compared to the HF group (10.9% and 3%) Eighteen (17.8%) patients in the HF group and 11 (10.4%) patients in the CL group had clinical manifestations of hypocalcemia Refractory hypocalcemia was recorded in two patients (2%) in the HF group and one (1%) patient in the CL group at months after surgery Postoperative endoscopic laryngostroboscopy showed EBSLN palsy in four patients (4%) in the HF group and in two patients (1.9 %) in the CL group During the follow-up of months, the findings of one patient in the HF group were ameliorated RLN palsy was noted in four patients (4%) in the HF group and in two patients (1.9%) in the CL group During the follow-up period, the findings were ameliorated in two patients in the HF group, and in one patient in the CL group The incidence of postoperative complications was similar in the groups (Table 2) Number of malign patients (all of them papillary thyroid cancer) were 45 in surgical specimens Twenty-five (55.6%) patients were papillary thyroid cancer in HF group and 20 (44.4%) in CL group of the surgical specimens The overall mean size of the tumor size of the surgical specimens for malign patients was 1.3 cm (range, 0.5e2.7 cm) The mean size of the tumor 1.2 cm (range, 0.5e2.5 cm) in HF group and 1.4 (range, 0.5e2.7 cm) in CL group There were two (4.4%) temporary SLN palsy patients was in the HF group and two (4.4%) in the CL group There was no significant difference in temporary SLN palsy between the study groups No permanent recurrent SLN palsy was encountered in any malign patients during the study period Discussion The present study, which primarily aimed to determine whether the EBSLN is safe during total thyroidectomies performed using HF, demonstrated that HF and conventional methods reveal similar outcomes The SLN is one of the branches of the vagus nerve, and has internal and external branches The internal branch, which provides sensory innervation to the larynx, is not at risk during thyroidectomy as it enters the larynx through the thyrohyoid membrane However, the external branch, which provides motor innervation of the cricothyroid muscle, which is involved in elongation of the vocal folds, has close anatomical relationship with the superior thyroid pedicle, and hence is susceptible to damage during thyroidectomy.5 The course of the EBSLN was described in various classification systems, including the classifications of Friedman et al,6 Kierner et al,7 and Cernea et al,8 the latter being the most used, and the risk is higher with nerves that are Grade IIa and IIb according to Cernea et al8 classification, where the nerve is in close proximity or on the upper pole of the gland In case of trauma, voice changes including hoarseness, voice fatigue, poor vocal volume, and projection may Table Postoperative complications Complications HF group (n Z 101) n (%) CL group (n Z 105) n (%) p Bleeding Seroma Hematoma Temporary hypocalcemia Permanent hypocalcemia Temporary SLN palsy Permanent SLN palsy Temporary RLN palsy Permanent RLN palsy (0) 11 (10.9) (3) 16 (15.8) (2) (4) (3) (4) (2) (2) 14 (13.9) (6.9) 10 (9.5) (1) (1.9) (1.9) (1.9) (1) 0.498 0.374 0.182 0.210 0.616 0.438 0.878 0.438 0.616 CL Z conventional ligation; HF Z harmonic focus; RLN Z recurrent laryngeal nerve; SLN Z superior laryngeal nerve Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic focus in total thyroidectomy? A prospective randomized study, Asian Journal of Surgery (2017), http://dx.doi.org/10.1016/j.asjsur.2016.12.004 + MODEL occur These changes often have a minimal impact on the patient’s life, excluding professional singers or public speakers In the literature, the reported incidence of EBSLN injury varies from 0% to 58%,9,10 and this high range may be attributed to the fact that EBSLN injury is mostly overlooked and this fact reflects a need for a standardized protocol and perhaps a move towards electromyography and video laryngostroboscopy for more accurate evaluation.11 EBSLN injury is not clearly defined clinically as injury to the recurrent laryngeal nerve Video laryngostroboscopy is a diagnostic tool in the assessment of EBSLN function, even when combined with voice analysis, and as a consequence electromyography and electroglottography have been recommended for post-thyroidectomy assessment An international standards guideline for intraoperative neuromonitoring (IONM) was proposed for the RLN in 2011,12 and recently the International Neural Monitoring Study Group published a guideline statement to optimize clinical utility of IONM for the management of the EBSLN.13 In a survey study in USA performed in in 2012, fellowship-trained surgeons and university surgeons more often search for the EBSLN during operation than nonfellowship-trained surgeons and nonuniversity colleagues.14 An international web-based survey in 2015 on surgeons from five continents, found that IONM was utilized in RLN management by 95% of respondents, for identification of the EBSLN by 26.3% of low-volume versus 68.4% of highvolume surgeons and 93% of the respondents felt IONM should be used in EBSLN identification in voice professionals.13 The meta-analysis performed between 2010 and 2016, showed more favorable results in terms of operative and postoperative parameters and cost-effectiveness, only Garas et al3 reported higher rates of RLN palsy in the ultrasound-based devices group; however, a retabulation of the studies included in Garas et al’s3 analysis indicated that persistent RLN paresis was present in 1/1006 cases in the ultrasonic arm and 2/992 cases in the conventional surgery arm However, Garas et al3 showed an increase in transient RLN palsy rate for harmonic scalpel.1e4,15 In the present study, the mean operative time was significantly shorter in the HF group than the CL group; however, drain necessity, duration of drainage, and duration of postoperative hospitalization and the incidence of postoperative complications was similar EBSLN palsy was noted in three and two patients, and RLN palsy was noted in two patients and one patient in the HF and groups, respectively at months Cheng et al4 claimed that it may be possible to reduce the rate of transient RLN paresis with the use of intraoperative nerve monitoring (IONM), as the improved dissecting ability of ultrasonic devices may decrease the amount of traction compared with conventional technique The cost of harmonic scalpels in thyroid surgery must also be discussed, since some authors have argued that this device is not cost-effective.16 However, it is commonly agreed that the potential added cost to the procedure by the use of the harmonic scalpel should be compared with the substantial benefit in surgical time-saving.17e19 Yildirim et al,20 who conducted a study on the use of harmonic scalpels in K Arslan et al Turkey, reported that increased cost of using harmonic scalpels was not significant Furthermore, they found that using the device at least 15 times reduces the price of surgery We did not a cost analysis of the present study, but we use every device at least 15 times The cost effectiveness of this device should be further investigated The present study has some limitations as it is a singleinstitution practice including a small sample size and all the surgeries were done or by supervised by two experienced surgeons, therefore the results of the study cannot be generalized However, to the best of our knowledge, it is the first study comparing conventional thyroidectomy to HF thyroidectomy, focusing on the function of the EBSLN using laryngostroboscopy In conclusion, the results of the study showed that HF is as safe as the conventional technique in terms of EBSLN However, interventions should be done no closer than mm to the nerves or glands, continuous activation of the device should be less than 15 seconds when approaching the nerve, the devices should not be used continuously, and, after prolonged application, cooling should be considered.2e15,21 We think that multicenter studies using neural monitoring and video laryngostroboscopy will allow the surgeons to get more information on the safety of nerves at risk during thyroidectomy Conflicts of interest All authors have no conflicts of interest to declare References Revelli L, Damiani G, Bianchi CB, et al Complications in thyroid surgery Harmonic scalpel, harmonic focus versus conventional hemostasis: a meta-analysis Int J Surg 2016; 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A network meta-analysis of surgical technologies Thyroid 2013;23:1138e1150 Cheng H, Soleas I, Ferko NC, Clymer JW, Amaral JF A systematic review and meta-analysis of Harmonic Focus in thyroidectomy compared to conventional techniques Thyroid Res 2015;1:8e15 Thiagarajan B, Ramamoorthy G Preventing nerve damage during thyroid surgeries Webmed Central Otorhinolaryngol 2012;3:WMC003260 Friedman M, LoSavio P, Ibrahim H Superior laryngeal nerve identification and preservation in thyroidectomy Arch Otolaryngol Head Neck Surg 2002;128:296e303 Kierner AC, Aigner M, Burian M The external branch of the superior laryngeal nerve: its topographical anatomy as related to surgery of the neck Arch Otolaryngol Head Neck Surg 1998; 124:301e303 Cernea CR, Ferraz AR, Nishio S, Dutra Jr A, Hojaij FC, dos Santos LR Surgical anatomy of the external branch of the superior laryngeal nerve Head Neck 1992;14:380e383 Aluffi P, Policarpo M, Cherovac C, Olina M, Dosdegani R, Pia F Post thyroidectomy superior laryngeal nerve injury Eur Arch Otorhinolaryngol 2001;258:451e454 Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic focus in total thyroidectomy? A prospective randomized study, Asian Journal of Surgery (2017), http://dx.doi.org/10.1016/j.asjsur.2016.12.004 + MODEL Harmonic focus in total thyroidectomy 10 Morton RP, Whitfield P, Al-Ali S Anatomical and surgical considerations of the external branch of the superior laryngeal nerve: a systematic review Clin Otolaryngol 2006;31: 368e374 11 Mihai R, Randolph GW Thyroid surgery, voice and the laryngeal examinationdtime for increased awareness and accurate evaluation World J Endocrine Surg 2009;1:1e5 12 Randolph GW, Dralle H, Abdullah H, et al Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: international standards guideline statement Laryngoscope 2011;121(suppl 1):1e16 ski M, Randolph GW, Cernea C International survey on 13 Barczyn the identification and neural monitoring of the EBSLN during thyroidectomy Laryngoscope 2016;126:285e291 14 Henry L, Helou L, Solomon N, Chang A, Libutti S, Stojadinovic A Current practice patterns regarding the conduct of thyroidectomy and parathyroidectomy amongst surgeons - a survey study J Cancer 2012;3:207e216 15 Cirocchi R, D’Ajello F, Trastulli S, et al Meta-analysis of thyroidectomy with ultrasonic dissector versus conventional clamp and tie World J Surg Oncol 2010;8:112 16 Leonard DS, Timon C Prospective trial of the ultrasonic dissector in thyroid surgery Head Neck 2008;30:904e908 ski M, Konturek A, Cichon S Minimally invasive video 17 Barczyn assisted thyreoidectomy (MIVAT) with and without use of harmonic scalpel A randomized study Langenbecks Arch Surg 2008;393:647e654 18 Ortega J, Sala C, Flor B, Lledo S Efficacy and costeffectiveness of the UltraCision harmonic scalpel in thyroid surgery: an analysis of 200 cases in a randomized trial J Laparoendosc Adv Surg Tech A 2004;14:9e12 19 Lombardi CP, Raffaelli M, Cicchetti A, et al The use of “harmonic scalpel” versus “knot tying” for conventional “open” thyroidectomy: results of a prospective randomized study Langenbecks Arch Surg 2008;393:627e631 20 Yildirim O, Umit T, Ebru M, et al Ultrasonic harmonic scalpel in thyroidectomies Adv Ther 2008;25:260e265 ski J, 21 Adamczewski Z, Kro ´l A, Kałuz_ na-Markowska K, Brzezin ski A, Dedecjus M Lateral spread of heat during thyLewin roidectomy using different hemostatic devices Ann Agric Environ Med 2015;22:491e494 Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic focus in total thyroidectomy? A prospective randomized study, Asian Journal of Surgery (2017), http://dx.doi.org/10.1016/j.asjsur.2016.12.004 ... avoid injury to the external branch of the superior laryngeal nerve (Figures 2e5) Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic. .. superior laryngeal nerve injury Eur Arch Otorhinolaryngol 2001;258:451e454 Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really safe when using harmonic focus. .. conventional ligation; HF Z harmonic focus; RLN Z recurrent laryngeal nerve; SLN Z superior laryngeal nerve Please cite this article in press as: Arslan K, et al., Is the superior laryngeal nerve really