Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2016; 20: 3544-3551 Study on the use of focus harmonic in thyroidectomies: is it useful also in preserving voice function?

A. MINNI 1, D. ROSATI 1, C. CAVALIERE 1, A. DE CARLO 1, G. ILLUMINATI 2, V. SCARANO CATANZARO 2, M. BONONI 3

1Department of Sensory Organs, “Sapienza” University of Rome, Azienda Policlinico Umberto I, Rome, Italy 2“F. Durante” Department of Surgical Science, “Sapienza” University of Rome, Azienda Policlinico Umberto I, Rome, Italy 3Department of “P. Valdoni”, “Sapienza” University of Rome, Azienda Policlinico Umberto I, Rome, Italy

Abstract. – OBJECTIVE : The aim of this ran - Key Words: domized study is to evaluate the real benefits of Thyroid surgery, Focus , Voice the FOCUS Harmonic Scalpel in total thyroidec - function . tomies compared with conventional ligation, re - garding operative time, postoperative blood loss, length of stay and complications. Further - Introduction more, as never seen in other studies, we studied the effects of using the FOCUS during thy - roidectomy analyzing the vocal production of During the past decades, the techniques of thy - patients before and after surgery. roid surgery have undergone small changes only. PATIENTS AND METHODS: We enrolled 361 On the other hand, the last twenty years have patients who underwent total thyroidectomy from 2008 to 2014. It was a randomized clinical trial in seen dynamic development of new instruments which all the surgical procedures were performed that has had a significant impact on this kind of by the same surgeon. Patients were randomized surgery 1-3 . into two groups according to the haemostatic Even if effective vessel haemostasis can be technique: 187 patients were included in a “con - achieved by using the conventional -and- ventional” group (C) in whom dissection and tie technique, newer techniques of vessel haemostasis were performed using conventional haemostasis were performed to be more rapid materials (Vicryl, stitches, V titanium hemostatic 4 clips and monopolar or bipolar electrocautery); while achieving the same effectiveness . 174 patients were included in a group in which Actually, during thyroidectomy , classic manu - the FOCUS was used (F group). al suture ligation and electrocoagulation are the RESULTS: Our data show that the FOCUS al - two main options to have a good haemostasis. lows a one-third time-saving vs. classic haemostasis. Moreover, the use of the FOCUS The first one is a time -consuming procedure and would allow reduced traction and reduced ma - implicates the risk of knot slipping, the second nipulation of the thyroid during surgery. Our da - one is a fast procedure but implicates the poten - ta demonstrate that the rate of complications in tial risk to damage surrounding tissues (i.e. la - the Focus group might not be significantly re - ryngeal nerve) by dispersion of heat 5. duced. In our series, we noticed that the quanti - In the last years, several papers have reported tative acoustic assessment of voice quality the utility of bipolar vessel sealing systems 6 or show important alterations in several parame - 7 ters (Shim, Jitt, sPPQ, sAPQ studied with the the Harmonic Scalpel in shortening the length of Multi Dimensional Voice Program evaluation) thyroid surgery and reducing blood loss, while between the C group and F group. maintaining a good safety and low rate of com - CONCLUSIONS: The FOCUS Harmonic Scalpel plications for patients . reduces the operative time, post-operative blood The FOCUS Harmonic Scalpel has been de - loss and length of hospital stay in thyroidectomy. Besides, important vocal alterations after thy - veloped for precise and simultaneous cutting as roidectomy seem more severe using the conven - well as hemostasis with minimal damage to sur - tional technique instead of FOCUS. rounding tissues; it uses high-frequency mechan -

3544 Corresponding Author: Antonio Minni, MD; e-mail: [email protected] Study on the use of focus harmonic scalpel in thyroidectomies ical energy to cut and coagulate at the same time 2. Coagulation disorders; tissues and vessels without the need for knot-ty - 3. Pregnancy; ing 8. 4. Cervicomediastinal goiters; The aim of this randomized study is to evalu - 5. Total thyroidectomy with need of lymph node ate the real benefits of the FOCUS Harmonic dissection as in patients with invasive malig - Scalpel in total thyroidectomies when compared nant cancer; with conventional ligation, concerning operative 6. Concomitant parathyroid disorders; time, postoperative blood loss, length of stay and 7. History of neck irradiation. complications. Besides, as never seen in other studies, we analyzed the effects of using the FO - In all cases, total thyroidectomy was per - CUS Harmonic Scalpel during thyroidectomy on formed under general anesthesia with endotra - vocal production of patients after surgery. cheal intubation . In both groups, the surgical in - cision was always a 4 to 6 cm low collar inci - sion; after performing subplatysmal flap with Patients and Methods high frequency electric knife, the superficial muscles were isolated at the midline. As the We enrolled 361 patients (152 men and 209 gland was exposed, we separated the two groups women) who underwent total thyroidectomy performing haemostasis of thyroid vessels in one from January 2008 to May 2014. It was a ran - of the following ways: (1) in the conventional domized clinical trial in which all the surgical group: main thyroid vessels (inferior , middle and procedures were performed under general anes - superior) were ligated using 3/0 silk sutures thesia by the same surgeon (to eliminate every while in all other vessels we used absorbable 4/0 kind of surgical technique bias) . sutures and/or electrocauterization ; (2) in the FO - Patients were randomized into two groups ac - CUS group : the haemostasis of all thyroid ves - cording to the haemostatic technique: 187 pa - sels was performed with the FOCUS Harmonic tients (79 men and 108 women) were included in Scalpel. For a better patient safety, we used a the first group (Conventional group or C group), double ligation technique on superior and inferi - in whom haemostasis and other surgical passages or thyroid vessels. Synthetically, the device was were performed using only conventional materi - used two times in 2 succeeding areas of the same als (Vicryl , stitches, haemostatic clips made of ti - vessel: just to coagulate the vessel in the distal tanium and monopolar or bipolar electrocoagula - part, and cutting the tissue after coagulation in tion ); 174 patients (73 men and 101 women) the proximal part. In this way , no suture ligation were included in FOCUS Harmonic scalpel was used. group (Focus group or F group), in which the Other surgical steps were the same for C FOCUS was used: the application of ultrasound group and F group . We identified and isolated re - to tissues was performed during the entire proce - current laryngeal nerves and parathyroid glands dure, to obtain three purposes synergistically: co - every time and a closed suction was always agulation, cutting, and cavitation . positioned below the superficial muscles. The patients were divided according to age, The parameters considered in this study were: preoperative diagnosis, and thyroid size to gener - total operating time (since initiation of the inci - ate homogeneous groups. sion until conclusion of skin closure), amount of drainage, time of positioning of drainage bal - The inclusion criteria were loons (the drains were removed if drainage vol - 1. Age > 18 years; ume was less than 10 ml in 24 hours) , post-oper - 2. Acceptance to participate in the study (signed ative hospitalization and occurrence of complica - informed consent form); tions (Table I). Serum parathyroid hormone, 3. Scheduled total thyroidectomy for multinodu - serum Ca and P levels were obtained in all pa - lar goiters or low risk differentiated carcinoma tients during the first post -operative day. We (T1N0M0). considered post-operative biochemical hy - poparathyroidism when serum parathyroid hor - The exclusion criteria were: mone level resulted below 15 ng/L (normal, 15- 1. Preoperative medication including analgesics, 65 ng/L ) and we handed out oral calcium carbon - corticosteroids or nonsteroidal antiinflamma - ate and calcitriol supplementation to patients tory drugs; with transient biochemical hypoparathyroidism,

3545 A. Minni, D. Rosati, C. Cavaliere, A. De Carlo, G. Illuminati, V. Scarano Catanzaro, M. Bononi

Table I. Operative and postoperative parameters between 2 groups.

Focus group Conventional group Variable (No. = 174) (No. = 187) p-value

Mean thyroid weight (g) 46.8 ± 18.5 50.6 ± 14.2 > 0.05 Total operating time (min) 78.8 ± 16.1 133.6 ± 33.4 < 0.05 Amount of drainage (ml) 36.9 ± 2.3 57.2 ± 4.4 < 0.05 Time of drainage (h) 36 ± 12 84 ± 12 < 0.05 Serum PTH (ng/L): Preoperative 46.90 ± 18.58 43.87 ± 17.21 > 0.05 Postoperative 20.6 ± 14.3 19.06 ± 16.88 > 0.05 Serum Ca (mmol/L): Preoperative 2.32 ± 0.13 2.28 ± 0.21 > 0.05 Postoperative 2.12 ± 0.17 2.05 ± 0.23 > 0.05 Serum P (mmol/L): Preoperative 1.36 ± 0.31 1.39 ± 0.33 > 0.05 Postoperative 1.45 ± 0.24 1.48 ± 0.27 > 0.05 Hypoparathyroidism 9 10 > 0.05. Postoperative hospitalization (d) 4.8 ± 1.28 6.9 ± 1.74 < 0.05 Parathyroid gland autotransplantation(n) 14 16 > 0.05. RLN paralysis: Temporary (n) 12> 0.05 Permanent (n) 00 Superior laryngeal nerve injury 00 Lymphatic ducts injured chyle leakage (n) 11> 0.05

Abbreviations: PTH, parathyroid hormone; RLN, recurrent laryngeal nerve. even if they didn’t show any clinical symptoms morphology and motility of the larynx , to as - of hypocalcemia. We defined recurrent laryngeal sess vocal fold vibratory pattern (mucosal nerve palsy as temporary when it resolved be - wave) and to appreciate symmetry and regu - tween 6 months after surgery and as permanent larity of the vocal fold vibration as well as when it persisted more than 6 months . signs of functional dysphonia. The examina - About the phoniatric part of the study, the pre- tion was video-recorded for every patient to operative and post-operative voice assessment eliminate any kind of bias. Esophageal-laryn - protocol included three procedures, performed in geal reflux (ELR) symptoms were reported ac - a single session : cording to the Reflux Finding Score 10 . 3. Spectrographyc analysis : the vocal quality of 1. Evaluation of Voice Handicap Index (VHI) : patients was evaluated by means of a software we submitted patients 30 questions about the tool for quantitative acoustic assessment of discomfort related to the use of their voice. voice quality (MDVP KAYPENTAX Mod. The VHI includes 30 items, each scored on a 5101). We selected the following acoustic pa - 5-point scale ranging from “never” to “al - rameters : Jitt (Jitter percent, the relative vari - ways”, divided into three subscales including ability of the pitch in the short-term); sPPQ functional, emotional and physical features re - (smoothed Pitch Perturbation Quotient); Shim lated to voice dysfunction. The normal limit (Shimmer percent, the relative variability of and threshold for significant changes were the peak-to-peak amplitude in the short-term) based on the values reported by Jacobson et and the sAPQ (smoothed Amplitude Perturba - al 9. A difference of up to 8 points on the sub - tion Quotient) . scales and 18 points on the total score was considered to indicate significant discomfort. The evaluation of vocal alterations using the 2. Laryngo-stroboscopy : we studied patients protocol of three procedures (VHI, laryngo-stro - performing a laryngeal examination using a boscopy and spectrographyc analysis with Multi 3.5 mm diameter fiberscope (Storz 11101RP) Dimensional Voice Program MDVP) showed in - connected to a stroboscopic light source (AT - teresting differences between C group and F MOS Endo Stroboscope L) to evaluate the group (Tables II, III, IV, V).

3546 Study on the use of focus harmonic scalpel in thyroidectomies

Table II. Pre-operative parameters in 152 men patients (one way Anova analysis).

Focus group Conventional group Variable (No. = 73) (No. = 79) p-value

Shim 2.54 2.73 > 0.05 sAPQ patients 2.88 2.94 > 0.05 Jitt 0.54 0.51 > 0.05 sPPQ 0.52 0.58 > 0.05 VHI p (perception of vocal patients 0.00 0.00 > 0.05 emission characteristics) VHI f (daily activities impact) 0.00 0.00 > 0.05 VHI e (psychological impact) 0.00 0.00 > 0.05

Table III. Pre-operative parameters in 209 women patients (one way Anova analysis).

Focus group Conventional group Variable (No. = 101) (No. = 108) p-value

Shim 2.21 2.17 > 0.05 sAPQ patients 2.44 2.35 > 0.05 Jitt 0.59 0.61 > 0.05 sPPQ 0.48 0.52 > 0.05 VHI p (perception of vocal patients 0.00 0.00 > 0.05 emission characteristics) VHI f (daily activities impact) 0.00 0.00 > 0.05 VHI e (psychological impact) 0.00 0.00 > 0.05

Table IV. Post-operative parameters in 152 men patients (one way Anova analysis).

Focus group Conventional group Variable (No. = 73) (No. = 79) p-value

Shim 3.95 5.78 ˂ 0.05 sAPQ patients 3.28 4.91 ˂ 0.05 Jitt 0.63 1.09 ˂ 0.05 sPPQ 0.62 1.28 ˂ 0.05 VHI p (perception of vocal patients 3.58 3.70 > 0.05 emission characteristics) VHI f (daily activities impact) 0.48 0.56 > 0.05 VHI e (psychological impact) 0.19 0.21 > 0.05

Table V. Post-operative parameters in 209 women patients (one way Anova analysis).

Focus group Conventional group Variable (No. = 101) (No. = 108) p-value

Shim 3.65 5.03 ˂ 0.05 sAPQ patients 4.26 5.95 ˂ 0.05 Jitt 0.72 1.21 ˂ 0.05 sPPQ 0.69 1.18 ˂ 0.05 VHI p (perception of vocal patients 4.18 4.31 > 0.05 emission characteristics) VHI f (daily activities impact) 0.98 1.09 > 0.05 VHI e (psychological impact) 0.89 0.96 > 0.05

(Shim: absolute shimmer, sAPQ: smoothed amplitude perturbation quotient, jitter: irregularity index of vibration glottic, sPPQ: Smoothed Pitch Period Perturbation Quotient, F0: fundamental frequency, vAm: peak to peak amplitude variation, VHI: Voice Handicap Index).

3547 A. Minni, D. Rosati, C. Cavaliere, A. De Carlo, G. Illuminati, V. Scarano Catanzaro, M. Bononi

Statistical Analysis Discussion Statistical analysis of the differences between groups was performed using the 2-sample t-test The thyroid gland has an extensive and com - and c2 test. Statistical analysis was made by plex vascular network . Therefore , it is essential SPSS 13 (SPSS Inc., Chicago, IL, USA) . p < to perform a good haemostasis to avoid postoper - 0.05 was considered statistically significant. ative hemorrhage which potentially causes pa - One-way ANOVA (Analysis of Variance) with tient’s asphyxia and death 11 . LSD procedure for the post hoc test were used to Besides, total thyroidectomy requires massive test the differences in the selected MDVP vari - clamp-and-tie maneuvers for the small thyroid ables in four subgroups ; p-values less than or vessels and if the use of conventional technique equal to 0.05 were considered to indicate signifi - is time -consuming, on the other hand using in - cance. Data were analyzed with a PC version of struments as mono or bipolar diathermy can be the Statistical Package for Social Sciences 16.0 unsafe because of the risk of damaging the sur - (SPSS Inc., Chicago, IL, USA). rounding structures caused by adjacent thermal spread. FOCUS Harmonic scalpel is a good solu - tion because it is a device specifically designed Results for having an accurate dissection and an efficient haemostasis in all the procedures realized in a All the parameters studied in the two groups narrow operating field as in thyroid surgery. were extensively presented in Table I . Total op - Even if previous harmonic scalpel instruments erating time (in minutes) was significantly short - were probably too much large and bulky, the er in F group (p < 0.05) ; this allowed a one -third Harmonic Focus is smaller and more maneuver - time saving in confront of C group . About post - able and probably for this reason many surgeons operative transient biochemical hypoparathy - use it as an alternative to conventional hand-tied roidism, it occurred more frequently in Classic ligation for haemostasis in thyroid surgery 12-16 . group than in Focus group, but this was not sta - The Harmonic Focus uses high frequency me - tistically significant, while about permanent bio - chanical energy to cut and coagulate tissues at the chemical hypoparathyroidism we did not register same time. Ultrasonic coagulation achieved by the any case . 3 temporary palsies of the recurrent la - FOCUS is similar to that of electrocautery because ryngeal nerve occurred (2 in the C group, 1 in the at last remains a denatured protein coagulum that F group), with full recovery in three months, but close blood vessels. Nevertheless, the mechanism we did not observe cases of permanent laryngeal by which the proteins become denatured is com - nerve palsy, derived probably from the accurate pletely different. Electrocautery and lasers form the and precise surgical technique and mostly from coagulum by heating tissue to denature the protein. knowledge and recognition of anatomical struc - The FOCUS instead denatures proteins by using ul - tures. We didn’t observe injuries to superior la - trasonic vibration and transferring mechanical ener - ryngeal nerve. gy sufficient to break tertiary hydrogen bonds and Intraoperative bleeding was not excessive in this allows to create a smaller area of adjacent ther - all the patients; so, there were neither blood mal damage compared to the bipolar cautery 17-19 . It transfusions nor postoperative definitive seque - is important to underline that using FOCUS, blood lae. The amount of total drainage was signifi - vessels with a diameter until 5 mm did not need for cantly higher in patients of C group vs patients of an additional protection by ligation, and this impli - F group . Besides, the days of drainage mainte - cates a significant decrease of total operative time nance before removal were significantly in - (about one third saving in confront of classic creased in C group compared with F group. The haemostasis in our study) and even a significant re - mean postoperative hospital stay was significant - duction of use of material (sutures, clips). ly reduced in the Focus group. The rate of Besides, we noticed that using FOCUS ultra - parathyroid gland autotransplantation was not sonic scalpel there was a significantly decreased statistically significant between Focus group and amount of drainage after surgery, and this is con - Classic group (Table I). firmed by numerous randomized trials that re - Two patients of C group with cervical ported an important intra -operative blood loss re - hematomas required re-exploration within 24 duction in addition to a post -operative drainage hours. No other postoperative complications decrease 20-31 . This led also to a reduction of post- were observed . operative hospital stay.

3548 Study on the use of focus harmonic scalpel in thyroidectomies

The reduced tissue injury and the better prelaryngeal muscles. An abnormal scarring after haemostasis are confirmed by the statistically dissection and suturing or even simple manipula - significant reduction of drainage volume for pa - tion during surgery may lead to a functional tients that we observed in the Focus group, even deficit 44 and this vocal individual deficit may if there are some authors that did not reach simi - constitute a moderate or severe handicap in pro - lar conclusions regarding the quantity of intra- fessional and social life of patients . operative and post-operative drainage 32-36 . We observed that in patients of C group the Furthermore, Miccoli et al 37,38 underline the re - quantitative acoustic assessment of voice quality duced traction and manipulation of thyroid al - showed important alterations in several parame - lowed by the use of Harmonic Focus (particular - ters, more evident in those concerning the vari - ly when the surgeon has to separate the upper ability of loudness than pitch, instead that pa - pedicle and cut the superior pole). tients of F group. Hence, to have a more accurate In the end, we observed that there wasn’t a voice acoustic evaluation, we studied the gener - significant difference of complication rate (hy - ally used relative variability of the pitch (Jitt) and poparathyroidism, superior and inferior laryngeal of the peak-to-peak amplitude (Shim) in the short nerve damages) between F group and C group. term, but even the smoothed corresponding para - The symptomatic cases of hypocalcemia of F meters (sPPQ and sAPQ). group were lower than C group , even if in our In our series, we noticed important differences study we didn’t find a significant difference at in foniatric parameters (Shim, Jitt, sPPQ, sAPQ) first post-operative day in PTH and calcium lev - studied with the MDVP evaluation between the el, which were considered as reliable parameters C group and F group. Specifically, patients who for parathyroid function evaluation 39 . underwent a thyroidectomy with conventional Perhaps, the decreased tissue damage resulting technique (C group) showed significantly worst from less heat produced by the FOCUS might values of pitch and amplitude vocal parameters lead to a reduced injury to the vascularization of than patients who underwent a thyroidectomy in parathyroids glands, but we need other series to which it was used FOCUS (Tables II, III, IV, V ). confirm it . The patients’ subjective perception of voice We observed 3 patients with temporary palsy discomfort evaluated with VHI was instead quite of recurrent laryngeal nerve which resolved with - similar between two groups. in 60 days, while we did not register permanent Our data, particularly the alterations found in palsy of the recurrent laryngeal nerve. the acoustic parameters related to peak-to-peak On the other hand, the main problem of FO - amplitude variability (Shim, sPPQ, sAPQ), sug - CUS is related to its cost 40-42 ; in fact, the Har - gest that in many patients we examined after monic Focus is a single-use and high-priced de - thyroidectomy with conventional technique (C vice and must be considered an additional cost group), the muscles of larynx were unable to for hospital. Anyway , we think that evaluating maintain a stable voice emission. Although we the decreased operating time and hospitalization, cannot directly attribute these findings to the the utilization of this instrument might be consid - thyroidectomy technique, we can assume that, ered advantageous. despite the preservation of the EBSLN, the sur - In a previous report 43 , we observed that after gical maneuvers we used for sectioning and re - total thyroidectomy, some patients showed some suturing the sternothyroid muscles in patients in vocal parameters alterations despite intra-opera - whom dissection and haemostasis were per - tive and post-operative integrity of both superior formed using conventional materials, could and inferior laryngeal nerves. We presumed that have induced fibrosis, thus, altering our pa - these alterations resulted from abnormal fibrosis tients’ laryngeal muscle balance. We suppose of prelaryngeal muscles after dissection and su - that surgically-related fibrosis might explain turing. why 45 , whereas in other series mild or severe For this reason, we controlled vocal parame - vocal changes reported reversed within a ters of patients that underwent a total thyroidec - month, in our patients , vocal alterations persist - tomy to observe if there was a correlation be - ed for one year or more 46 . Finally , we can af - tween surgical technique and vocal parameters firm that, using FOCUS, is possible to avoid the related to eventual fibrosis and abnormal scarring muscular resection of pre-thyroid muscles, thus of laryngotracheal unit. After thyroidectomy, the performing a less traumatic injury to the tissues laryngotracheal unit is supported only by the and a smaller fibrosis .

3549 A. Minni, D. Rosati, C. Cavaliere, A. De Carlo, G. Illuminati, V. Scarano Catanzaro, M. Bononi

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3550 Study on the use of focus harmonic scalpel in thyroidectomies

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