Although the survival rate of patients with thyroid cancer has remained unchanged,1 the incidence of thyroid cancer has been steadily increasing,2 leading to innovations in approaches to thyroid surgery.
In addition to conventional open thyroidectomy (OT), the endoscopic breast approach, endoscopic and robotic bilateral axillo-breast approach (BABA), as well as endoscopic and robotic transaxillary, and endoscopic and robotic facelift approaches, have been introduced to improve patients’ quality of life by focusing on better cosmetic outcomes and lesser postoperative pain.3 BABA is a common technique used to avoid cosmetically undesirable scars. Notably, BABA thyroidectomy using the da Vinci surgical robot system is more popular than the endoscopic BABA method because the number of central lymph nodes resected is higher and surgical complication and locoregional recurrence rates are lower with the former technique.4
Although the cosmetic benefit of robotic thyroidectomy (RT) is widely reported, the severity of postoperative pain in patients undergoing RT or OT is debatable. A few studies have reported that postoperative pain associated with both the methods was similar,5,6 whereas others have reported that RT resulted in lesser postoperative pain.7,8 Comparative studies investigating postoperative pain after BABA thyroidectomy are limited. We compared postoperative pain after OT and BABA RT (BRT) using propensity score matching analysis. We additionally compared the incidence and severity of postoperative nausea and vomiting (PONV) in patients undergoing the aforementioned surgical procedures.
MATERIALS AND METHODS
The Institutional Review Board of Chung-Ang University Hospital approved this study (IRB no. 2016-2097), and the requirement for informed consent was waived. We analyzed the electronic medical records of 1269 patients who were diagnosed with thyroid cancer, nodular goiter, and follicular neoplasm, and underwent OT or RT at the Chung-Ang University Hospital between January 1, 2010 and April 30, 2016. We anonymized all the data from the electronic medical records. We excluded patients aged younger than 19 years, patients who underwent concomitant surgeries, patients in whom data for variables or outcome parameters were missing, patients who had previously participated in other randomized controlled trials, and those who refused fentanyl-based intravenous patient-controlled analgesia (IV-PCA). We categorized patients on the basis of the surgical procedure performed into the OT group (n=1128) and the BRT group (n=141). This manuscript has been prepared per the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology checklist.9
Data collection was performed by a specialized nurse who obtained information related to PCA, including data regarding patient management. This nurse was specially trained for data collection with respect to pain and PONV, and all the data were recorded in a standardized form. The severity of pain was evaluated using a 10-point visual analogue scale (VAS), whereas the severity of nausea was evaluated using a numerical rating scale (NRS) (none=0, mild=1, moderate=2, severe=3, and worst imaginable=4). The variables were evaluated on postoperative days (PODs) 0 and 1.
Standardized treatment protocols for IV-PCA were used in this study. The IV-PCA (100 mL) regimen used for thyroidectomy consisted of 15 mcg/kg of fentanyl and 90 mg of ketorolac or 60 mg of nefopam (administered as a continuous infusion at 1 mL/h, bolus infusion of 1 mL, with a lockout interval of 15 min). Additional rescue analgesics (ketorolac 30 mg, nefopam 20 mg, or fentanyl 50 mcg) were administered through the IV route if the VAS score for pain was >3 or if patients requested analgesia despite the use of IV-PCA. Rescue antiemetics (metoclopramide 10 mg, ramosetron 0.3 mg, palonosetron 0.25 mg, or granisetron 3 mg) were administered through the IV route in patients with NRS >moderate score or if patients requested an antiemetic.
All data were systematized on the basis of the following predefined criteria: surgical method (OT vs. RT), operation time, patient characteristics (age, sex, height, weight, and smoking history), PONV or motion sickness, anesthesia used [type of anesthetic agent administered (desflurane vs. sevoflurane vs. propofol) and use of intraoperative opioid], and dosage of IV-PCA. The following additional postoperative variables were used for data systematization: postoperative pain, usage of rescue analgesics, incidence and severity of PONV, usage of rescue antiemetics, and incidence of headache.
Group allocation of patients is not randomized in retrospective cohort studies; thus, various confounders may affect the results of such studies. We used propensity score matching to analyze our data to reduce the above-mentioned bias. Logistic regression analysis was used to calculate propensity scores and analyze the covariates (age, sex, height, weight, smoking history, PONV or motion sickness, operation time, dosage of intraoperative opioid, and dosage of fentanyl used in IV-PCA). We used the nearest available match between groups based on propensity score similarities (caliper radius of 0.001). Standardized difference (STD), defined as the intergroup difference in means expressed as a unit of SD, was calculated to assess whether the matched groups were adequately balanced. An STD value <20% indicated reliable and effective intergroup comparison.10
After matching, we assessed the type of thyroid disease, the size of thyroid, and the extent of operation performed in each matched group.
We used the Shapiro-Wilk test to evaluate the distribution of continuous variables. We compared normally distributed data using parametric and non-normally distributed data using nonparametric methods. We used an unpaired t test or the Mann-Whitney U test for continuous variables, and a χ2 or the Fisher exact test for descriptive variables. After data matching, the paired t test, Wilcoxon signed-rank test, and McNamara test were used for statistical intergroup comparisons. Continuous variables were expressed as mean±SD, whereas descriptive variables were expressed as absolute numbers (%).
All statistical analyses were performed using the IBM Statistical Package for Social Sciences Statistics, Version 23 (IBM Corp., Armonk, NY). A P-value<0.05 was considered statistically significant.
We obtained the records of 1269 patients who underwent OT or RT at Chung-Ang University Hospital between January 1, 2010 and April 30, 2016. On the basis of the surgical method used, patients were categorized into an OT group (n=1128) and a BRT group (n=141). Demographic characteristics of all patients and the matched data are shown in Table 1.
Comparison Between the OT Versus BRT Groups in the Overall Series
Before propensity score matching, 9 of the 17 confounders (age, height, weight, operation time, sevoflurane, desflurane, nitrous oxide, continuous infusion of propofol, and remifentanil use) showed poor STD scores (Table 1). No significant intergroup differences were observed in any of the variables postoperatively (Table 2).
Comparison Between the OT Versus BRT Groups Based on Propensity Score Analysis
Using propensity score analysis, 86 patients were matched in each group. Acceptable STD values (<20%) were observed for all 17 confounders; thus, we could confirm that all covariates were well balanced in the matched groups (Table 1). The VAS score for pain on POD 0 was higher in the OT than in the BRT group (2.57±0.95 vs. 2.28±0.95, P=0.040). However, no statistically significant intergroup differences were observed in the use of rescue analgesics on POD 0 [1 (1.2%) vs. 3 (3.5%), P=0.312], the VAS score for pain on POD 1 (1.09±0.76 vs. 0.93±0.76, P=0.244), and the use of rescue analgesics on POD 1 [1 (1.2%) vs. 1 (1.2%), P=1.000] (Table 3).
No significant intergroup differences were observed in the type of thyroid disease, the size of thyroid, and the extent of operation performed (Table 4).
In this study, the VAS score for pain on POD 0 was higher in patients who underwent OT than in patients who underwent BRT. However, no statistically significant intergroup difference was observed in the use of rescue analgesics. No statistically significant intergroup difference was observed in the VAS score for pain and the use of rescue analgesics on POD 1 and in the NRS score for nausea and the use of rescue antiemetics.
Linear regression analysis of data showing cancer incidence between 1999 and 2013 obtained from the Korea National Cancer Incidence Database indicates that thyroid cancer was the most common cancer in women aged 35 to 64 years and in both sexes in the age groups 0 to 14 and 15 to 34 years.11 The prevalence of thyroid cancer has increased significantly in recent years, with a reported increase of 246% from 1995 to 2002.12
Higher costs, the need for greater technological skills and for advanced surgical training serve as disadvantages of RT.13 However, it scores over OT or endoscopic thyroidectomy14 in that RT offers high-definition 3-dimensional visualization of the surgical field,15,16 which allows surgeons to perform delicate movements and offers better maneuverability to access even narrow and deep-seated structures.17,18 In addition to technical advantages, RT scores over OT by providing better cosmetic outcomes because the RT incision is not easily visible, whereas that used for OT is more conspicuous because it is located in the anterior neck.19,20 This cosmetic advantage particularly benefits patients with hypertrophic scar formation or keloid diathesis.
BABA is one of the most popular RT techniques used in clinical practice. BABA is associated with better cosmetic outcomes, and performing contralateral thyroidectomy is easier with the BABA than with the transaxillary approach.21 The BABA uses 2 axillary incisions measuring 8 mm in size, as well as 8- and 12-mm circumareolar incisions on each side15 (Fig. 1). This technique provides symmetrical views of each thyroid lobe (as is possible during OT) and better visualization of important structures such as the recurrent laryngeal nerve and the superior and inferior thyroid vessels.15 Excluding the aforementioned technical advantages, the BABA and OT techniques do not differ with respect to surgical completeness.16
The width of the flaps created using the BABA technique is 3- to 4-fold greater than that of the flaps created during OT; thus, theoretically, the former can potentially be associated with more severe postoperative pain.
Previous studies have reported that RT was associated with more severe anterior chest pain caused by electrocautery induced thermal injury and subcutaneous traction applied during wide dissection required during RT.22 Moreover, although anterior chest pain associated with RT was more severe than that associated with OT, the level of neck pain was comparable over a few months postoperatively.23,24 Sensory changes in the anterior chest area, such as light pressure thresholds persisted over 3 months postoperatively.25
In contrast, a few studies have reported similar degrees of postoperative pain after OT or RT.5 Furthermore, physical distress levels including pain and exercise limitations did not differ between BRT and OT.26
We did not characterize postoperative pain location-wise such as neck or anterior chest pain, however, postoperative pain was lower after BRT than after OT. This result concurred with previous studies, which have reported lower pain scores in patients undergoing RT.6–8
The lower pain scores observed after BRT (despite the wider flap dissection) could be attributed to differences in the incision site. OT involves anterior neck incision. The anterior neck has a more extensive nerve distribution and shows greater mobility than the axilla or the areola (the incision site for BRT), which may cause greater mobilization of and traction on the parathyroid tissue intraoperatively with a consequent increase in postoperative pain after OT. Previous studies7,8 have reported no difference in pain 4 hours postoperatively but statistically significant difference in pain 24 hours later, which may be attributed to excessive neck movements in patients undergoing OT.
Although a significant intergroup difference was observed in VAS scores on POD 0, the absolute difference in VAS scores between the groups was relatively small, which could be attributed to the fact that we only included patients receiving fentanyl-based IV-PCA for pain control. Use of opioid-based PCA may have reduced postoperative pain in both the groups, with a consequent decrease in absolute VAS scores in both the groups, resulting in only a slight difference in VAS scores (2.57 vs. 2.28, difference 0.29).
The etiology of PONV is multifactorial and includes anesthetics used and surgical factors.27,28 Previous studies have reported a high incidence of PONV in patients undergoing thyroidectomy,29,30 which may be associated with patient characteristics (mostly young or middle-aged women were included in the study). Excessive stimulation of the vagal afferent nerve during surgical manipulation is also known to increase the incidence of PONV.29 Furthermore, postoperative pain is a common etiological factor associated with PONV.28,31 The increased incidence of PONV could be associated with the use of fentanyl-based IV-PCA. Perioperative use of opioids is a well-known risk factor for PONV.
A previous study comparing open and gasless transaxillary RT has shown lower incidence and severity of PONV in the latter group,8 which could be explained by lesser vagal stimulation and postoperative pain observed with transaxillary RT than with OT. Our study showed no intergroup difference in the severity of PONV. Despite lesser vagal stimulation and postoperative pain with BRT than with OT, our observations regarding PONV may be attributed to carbon dioxide (CO2) insufflation performed during BRT (this procedure is not performed during OT or transaxillary RT). CO2 insufflation dilates cerebral vessels and increases intracranial pressure and is an independent risk factor for PONV.32,33 In our view, these characteristics of CO2 insufflation could have offset the positive effect of RT on the reduction of PONV.
The limitations of our study are as follows: (1) the retrospective study design is a drawback in that missing or incomplete data, as well as recall bias when evaluating VAS and NRS scores could have affected our results. (2) This study was not a randomized clinical trial; thus, the role of confounders cannot be excluded. However, we did our best to analogize the best correlation on the basis of the results of this study by performing propensity score matching. (3) We only assessed patients with IV-PCA for short term (days 0 and 1). Therefore, long-term VAS for pain and NRS for nausea, and those for patients without IV-PCA, were not included in this study and these data could induce different result. (4) This study analyzed data from a single medical center focusing only on Asians. Studies involving patients of other ethnicities with higher body mass index and breast volume (which could interfere with the working space required for RT) could show different results. Therefore, the results of this study are not generalizable. Further randomized controlled trials and multicenter studies are warranted to validate our findings.
In conclusions, although flap dissection was larger and the operation time was longer in the BRT than in the OT group, no significant intergroup differences were observed in postoperative pain, except on POD 0. Thus, the cosmetic benefit offered by BRT and the lesser pain on POD 0 may significantly contribute to better quality of life and patient satisfaction, which might explain patients’ preference for BRT observed in clinical practice.
The authors thank Min Seo Kim for assistance with illustrations in the manuscript.
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