ORIGINAL ARTICLE
Long-term prospective evaluation comparing robotic parathyroidectomy with minimally invasive open parathyroidectomy for primary hyperparathyroidism Neil Tolley, MD, FRCS, DLO,1 George Garas, MRCS, DOHNS,1 Fausto Palazzo, MS, FRCS,2 Alexa Prichard, MBBS,1 Konstantinos Chaidas, MD, PhD,1 Jeremy Cox, MD, FRCP,3 Ara Darzi, KBE, MD, FRCS,4 Asit Arora, MRCS, DOHNS1* 1
Department of Otorhinolaryngology and Head & Neck Surgery, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom, 2Department of Endocrine and Thyroid Surgery, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom, 3Department of Endocrinology, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom, 4Department of Surgery and Cancer, Imperial College London, St. Mary’s Hospital Campus, London, United Kingdom.
Accepted 18 December 2014 Published online 26 June 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23990
ABSTRACT: Background. Targeted parathyroidectomy is a popular technique for localized pathology. No single technique is established as superior. The purpose of this study was to compare robotic-assisted parathyroidectomy (RAP) with the most common approach. Methods. This was a prospective, nonrandomized study. Fifteen consecutive patients who underwent RAP were compared to 15 matched controls undergoing focused lateral parathyroidectomy (FLP). Results. Biochemical cure occurred in 29 of 30 patients (97%). No major complications occurred, although there was 1 robotic conversion. RAP demonstrated a significant time reduction (R2 5 0.436; p 5 .01) but took much longer to perform than FLP (119 minutes vs 34 minutes; p 5 .001).
INTRODUCTION Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder after diabetes mellitus and osteoporosis.1 Although the exact incidence is unknown, its prevalence is estimated at between 1 to 4 of 1000 with a 3:1 female to male ratio.2 Approximately 80% of PHPT are due to a solitary parathyroid adenoma. Multigland disease in the form of multiple adenomas or parathyroid hyperplasia accounts for the remaining cases.2,3 Surgery remains the only definitive cure for PHPT and this has changed considerably since Felix Mandel performed the first successful parathyroidectomy in 1925.3,4 Over the decades, the surgical approach evolved into a standardized exploration of the neck via a “collar” incision. The objective has been to identify all the parathyroid glands, leaving the normal glands in situ and
*Corresponding author: A. Arora, Department of Otorhinolaryngology and Head & Neck Surgery, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, Praed Street, London, United Kingdom, W2 1NY. E-mail: [email protected] The preliminary findings of this study were presented at the 2011 British Association of Endocrine & Thyroid Surgeons annual meeting; September 22–23, 2011, Poitiers, France, where it was awarded the best poster presentation prize and also as a podium presentation at both the 2012 American Academy of Otolaryngology-Head and Neck Surgery & OTO EXPO, September 9–12, 2012, Washington, DC; and 20th International Federation of Oto-Rhino-Laryngological Societies World Congress, June 1–5, 2013, Seoul, Korea.
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RAP was associated with less initial postoperative pain (p 5 .036) and higher satisfaction with scar cosmesis (p 5 .002) until 6 months. Quality of life (QOL) improved in both groups (p 5 .007). Conclusion. RAP provides superior early cosmesis with equivalent global health improvement compared to FLP. The high cost and learning curve may preclude widespread adoption. Further evaluation is necessary to C 2015 Wiley establish its clinical efficacy regarding scar cosmesis. V Periodicals, Inc. Head Neck 38: E300–E7, 2016
KEY WORDS: robotic, surgery, hyperparathyroidism, cosmesis, outcomes
removing the diseased gland or glands. In the past 3 decades, there has been a significant improvement in the accuracy of preoperative localization studies. The reliable identification of a parathyroid adenoma has created the right background for a targeted surgical approach making targeted parathyroidectomy a well-established approach in the 65% of patients with localized single-gland pathology.5 A variety of targeted, minimal access techniques have been described. Despite numerous options, no single technique is established as demonstrably superior.6 However, the focused lateral parathyroidectomy (FLP) is the most widely adopted because of its simplicity and the lack of requirement for any additional equipment while offering cure and complication rates equivalent to both the conventional and other minimal access techniques.7–9 Advantages over the former include reduced operating times, smaller scars, shorter hospital stays, and less postoperative analgesic requirement.10 More recently, the endoscopic “scar-less in the neck” approach has been described. Studies suggest that avoiding a neck scar improves patient satisfaction.11–13 However, this approach has not been widely adopted because of limitations associated with the endoscopic platform. These include suboptimal depth perception because of a 2D view and restricted instrument movement because of the narrow working space.14 The da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced to address these limitations.15
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The dual-channel endoscope permits image magnification with the additional benefit of a 3D view of the operative field and superior depth perception compared to conventional endoscopy. The console surgeon controls 5 mm “wristed” instruments. This allows precise tissue manipulation within the confined space of the anterior neck compartment. The tremor filtering and motion scaling features enhance surgical dexterity.16 Feasibility studies of robotic-assisted parathyroidectomy (RAP) using an infraclavicular5 or transaxillary approach have been reported.17,18 However, the clinical efficacy of this approach compared to conventional targeted parathyroidectomy is not established. Therefore, the purpose of this study was to compare the outcome of RAP and FLP. The objective was to establish whether RAP conferred any additional benefit.
MATERIALS AND METHODS Ethical approval The study received favorable approval from the National Health Service Health Research Authority (National Research Ethics Service Committee London, Protocol Reference Number: 08/H0721/97).
Study design A prospective comparative study was conducted. Patients were recruited between April 2009 and December 2010 from the Departments of Otorhinolaryngology and Head & Neck Surgery (St. Mary’s Hospital Campus) and Endocrine and Thyroid Surgery (Hammersmith Hospital Campus), Imperial College Healthcare NHS Trust, London, UK. The unit does approximately 200 parathyroidectomy cases per annum and all cases are entered in the national British Association of Endocrine and Thyroid Surgeons database. Fifteen unselected consecutive FLPs and 15 consecutive RAPs were compared. The selection criteria were the same for both patients who underwent FLP and RAP, as described below. Both approaches were offered to all patients who met those criteria and the first 15 patients that opted for FLP were compared with the first 15 that opted for RAP. This was done to minimize differences between the groups (eg, age, body mass index [BMI], and localization) other than the approach used, in view of the lack of randomization.
Selection criteria Criteria included a biochemical diagnosis of PHPT because of a single parathyroid adenoma on imaging. Triple modality concordant localization using ultrasonography, sestamibi, and single-photon emission CT was a prerequisite to be considered for study inclusion. The diagnosis required an albumin-adjusted serum total calcium >2.60 mmoll21 on repeat samples, with an elevated parathyroid hormone (PTH) of >6.8 pmoll21 taken concurrently. Interfering medications, such as thiazide diuretics or lithium, were discontinued before testing. Familial hypocalciuric hypercalcemia was excluded by measuring 24-hour urine calcium levels. All patients had a 24-hour urine calcium >5 mmol, and/or a 24-hour urine calcium/creatinine clearance ratio >0.01. Patients with a family history of PHPT or associated endocrine condi-
tions, evidence of thyroiditis or bulky thyroid disease, and/or previous neck surgery or irradiation were not eligible for inclusion in this study.
Patients Thirty patients were recruited. The patient demographics, BMI, biochemical data, and radiological localization of the parathyroid adenoma are summarized in Table 1.
Treatment allocation The selection of a robotic versus a conventional approach was based upon patient preference (see Study design). Both approaches were offered to all patients. All RAP cases were performed by the same console and bedside surgeon (N.S.T. and A.A., respectively). FLP was performed by 1 of 2 senior surgeons (N.S.T. and F.P.) scrubbed in with an assistant surgeon (A.A.). Both senior surgeons were experienced with FLP each having performed over 300 cases.
Surgical technique Robotic-assisted parathyroidectomy. The surgical approach has been described in detail in a previous publication.5 The robotic arm is maintained in the neutral position. An infraclavicular incision is made ipsilateral to the adenoma. The exact position of the incision depends on body habitus and patient preference. It is drawn with the patient awake to ensure it is concealed even when wearing low-cut tops. Dissection proceeds through the natural dehiscence between the sternal and clavicular insertions to expose the internal jugular vein, common carotid artery, and ipsilateral omohyoid and sternohyoid muscles. A self-retaining (Chung or Imperial) retractor is used to maintain sufficient working space and 2 additional 5-mm trocar incisions are made in the anterior axillary line. Again, the exact positions vary. Most commonly, the first stab incision is made at the superior part of that line at the level of the pectoralis major tendon with the lower being made about 4 cm below. If body habitus permits, the 5 mm inferior trocar is inserted via an ipsilateral periareolar incision instead (see Figure 1). The remaining dissection is performed with the da Vinci robot. Drains are not inserted. Focused lateral parathyroidectomy. The technique described by Agarwal et al19 was used. An ipsilateral mini cervicotomy is made over the anterior border of the sternocleidomastoid muscle at a level depending on the position of the adenoma. The subplatysmal flaps are raised via sharp and blunt dissection. Dissection is performed lateral to the strap muscles to obtain access to the posterolateral thyroid lobe. After excision of the parathyroid adenoma and hemostasis, closure is achieved in a 2-layer format. No drains are used.
Outcome measures and follow-up The success of the procedure was determined biochemically with normalization of the albumin-adjusted serum total calcium and PTH levels after surgery and by histopathological confirmation of the presence of hypercellular parathyroid tissue in the excised lesion. HEAD & NECK—DOI 10.1002/HED
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TABLE 1. Patient demographics, body mass index, preoperative biochemical data, and radiological localization of the parathyroid adenoma.
Case
RAP 1 RAP 2 RAP 3 RAP 4 RAP 5 RAP 6 RAP 7 RAP 8 RAP 9 RAP 10 RAP 11 RAP 12 RAP 13 RAP 14 RAP 15 Control 1 Control 2 Control 3 Control 4 Control 5 Control 6 Control 7 Control 8 Control 9 Control 10 Control 11 Control 12 Control 13 Control 14 Control 15
Sex
Age, y
BMI, kg22
Ethnic origin
Preoperative PTH, pmoll21
Preoperative corrected calcium, mmoll21
Localization
Female Male Female Female Female Female Male Male Female Female Female Female Female Female Female Male Female Female Female Female Female Female Male Female Female Female Female Female Female Female
72 49 49 70 46 68 79 50 58 58 48 51 75 42 67 54 46 45 46 70 70 63 75 50 38 46 58 63 57 74
24.8 26.1 27.4 25.3 28.5 27.7 22.5 33.4 22.8 23.8 27.9 21.5 26.6 27.5 28.9 25.9 28.9 31.8 23.4 28.7 27.2 25.9 28.1 25.4 26.9 27.8 24.9 31.7 26.7 24.6
White Asian White Afro-Caribbean Afro-Caribbean White Afro-Caribbean White White White White White White White Afro-Caribbean White White White White Asian White Asian Afro-Caribbean White White Asian White Asian White Asian
12.5 15.7 34.0 15.6 16.0 11.4 27.9 21.2 15.3 15.3 30.7 11.4 19.7 14.2 17.9 13.0 21.5 13.2 22.9 11.7 14.6 7.1 18.8 26.4 14.8 26.1 63.3 26.1 14.2 16.0
2.61 2.62 2.96 2.66 3.07 2.80 2.95 2.99 2.67 2.85 2.75 2.61 2.78 2.66 2.75 2.61 2.76 2.70 2.68 2.70 2.78 2.81 3.01 2.93 2.71 2.66 3.20 2.63 2.91 2.80
Left inferior Right inferior Left inferior Left inferior Right inferior Left inferior Right inferior Right superior Left inferior Left inferior Left inferior Right superior Right superior Right inferior Left inferior Left superior Left inferior Left superior Right inferior Right inferior Right inferior Right superior Left superior Right superior Right inferior Left inferior Left inferior Left inferior Right superior Right superior
Abbreviations: BMI, body mass index; PTH, parathyroid hormone; RAP, robotic-assisted parathyroidectomy. Normal range: PTH 5 1.1–6.8 pmoll21; corrected calcium 5 2.15–2.60 mmoll21.
Patient-reported outcome measures included prospective assessment of scar cosmesis, pain, voice disability, and global health using validated assessment tools. Scar cosmesis was assessed using a 0 to 100 visual analog scale (VAS), in which 100 represented “completely satisfied.” Pain was assessed using a 0 to 100 VAS, in which 100 represented “worst imaginable pain.” The pain management was the same in both groups. All patients were given regular oral acetaminophen 1 g every 6 hours and ibuprofen 400 mg every 8 hours. Voice satisfaction was rated using the Voice Handicap Index-2 questionnaire. Moreover, all patients had preoperative and postoperative laryngoscopy. Global quality of life (QOL) was assessed using the EuroQOL-5D questionnaire assessment tool that comprises a descriptive system and EuroQOL-visual analog scale. The former comprises 5 dimensions: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each is self-rated as 1 5 no problems, 2 5 some problems, and 3 5 severe problems. The EuroQOL-visual analog scale is a 0 to 100 scale in which 100 represented “best imaginable health state.”
Statistical analysis The 2 groups were compared regarding the patients’ characteristics, intraoperative findings, and postoperative results using chi-square test (categorical variables) or E302
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Mann–Whitney and Wilcoxon test (continuous variables). A logarithmic regression model was used to evaluate the robotic learning curve for the time taken to perform the robotic procedure. The comparisons were performed using SPSS software version 21.0 (SPSS, Chicago, IL). Statistical significance was accepted when p < .05.
RESULTS Patients The RAP and FLP groups were matched in terms of age (58.8 6 12.0 years vs 57.0 6 11.8 years, respectively; p 5 .618), sex (3 of 15 men vs 2 of 15 men, respectively; p 5 .624), race, BMI (26.3 6 3.0 kg22 vs 27.2 6 2.4 kg22, respectively; p 5 .436), size of lesion (21.7 6 6.4 mm vs 17.5 6 6.8 mm, respectively; p 5 .118), and comorbidity.
Operative data The mean incision length for the robotic approach was 3.9 cm, whereas for the open approach it was 3.6 cm (p 5 .293). The parathyroid adenoma was successfully identified and removed in all cases. Pathological evaluation of the excised specimen confirmed hypercellular parathyroid tissue. The mean blood loss was 9.9 6 3.9 mL in the robotic group and 11.6 6 2.6 mL in the conventional group (p 5 .056). One RAP case was converted to an open procedure because
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and PTH normalized postoperatively in 14 patients. One patient had persistent hyperparathyroidism but declined further investigation or treatment. The remaining 29 patients were normocalcemic at latest follow-up (minimum 12-month timeframe after surgery).
Postoperative complications One postoperative complication occurred in the robotic cohort (RAP case 11). A superficial wound infection was treated with oral antibiotics (co-amoxiclav) with no adverse clinical outcome.
Patient-reported outcome measures
FIGURE 1. Incisions for right robotic-assisted parathyroidectomy marked in red. All incisions are ipsilateral. Exact positions can vary as they depend on body habitus and patient preference. The infraclavicular incision is drawn with the patient awake to ensure it is concealed even when wearing low-cut tops. The first stab incision is made at the superior part of the anterior axillary line at the level of the pectoralis major tendon with the lower made about 4 cm below. If body habitus permits, the 5 mm inferior trocar is inserted via an ipsilateral periareolar incision instead, as indicated.
Patients were followed up after surgery for a mean period of 24.8 6 14 months. Postoperative pain at 2 weeks was significantly less for patients in the RAP group compared to those in the FLP group (6.43 6 9.7 vs 24.33 6 24.1, respectively; p 5 .036). Regarding scar cosmesis, the mean VAS score was significantly higher for the robotic group compared to the FLP group at 3 months (91.3 6 9.2 vs 65.7 6 19.2, respectively; p 5 .005) and 6 months (92.8 6 7.7 vs 70.7 6 19.2, respectively; p 5 .002) after surgery, but not at 12 months (94.3 6 5.8 vs 80.4 6 28.4, respectively; p 5 .523) and 24 months (95 6 5.0 vs 81.7 6 35.3, respectively; p 5 .849; see Figure 3). There was no difference in global QOL between the groups (see Figure 4), which significantly improved up to 1 year after surgery in both groups (p 5 .007 for the RAP group and p 5 .043 for the FLP group; see Figure 5). All patients had preoperative and postoperative laryngoscopy. Postoperative laryngoscopy was performed on the first postoperative day and confirmed normal vocal cord mobility in all patients (n 5 30). Significant voice disability was not reported after surgery using the Voice Handicap Index-2 questionnaire. All patients were discharged within 24 hours.
DISCUSSION Targeted parathyroidectomy is a popular surgical option for PHPT when the abnormal parathyroid gland has been of suboptimal surgical access owing to the patient’s large body habitus (RAP case #8; BMI 5 33.4 kg22). The mean operative time was significantly higher for RAP compared to FLP (119 minutes vs 34 minutes, respectively; p 5 .001). In the robotic cohort, a clear learning curve was demonstrated (see Figure 2). Logarithmic regression analysis (excluding the 1 conversion) revealed a progressive reduction in operating time from 190 minutes to 57 minutes (R2 5 0.436; p 5 .01).
Biochemistry The postoperative biochemical data, intraoperative localization findings, and histopathological dimensions are shown in Table 2. The mean biochemical follow-up was 27 6 12.2 months. There was no difference in the cure rate between groups (p 5 .543). In the robotic cohort, initial normalization of PTH and adjusted serum calcium levels occurred in 13 patients. The remaining 2 patients had persistent hyperparathyroidism because of 4-gland hyperplasia not detected on the initial localization imaging. Further surgery involving bilateral neck exploration cured them. In the FLP group, adjusted serum calcium
FIGURE 2. Learning curve regarding operative time (in minutes) for robotic-assisted parathyroidectomy (RAP). Case #8, which necessitated conversion to open surgery (body mass index [BMI] 5 33.4) was excluded from the analysis. y 5 180.9435 1 (233.5482 * log(x)) R 5 0.661, R2 5 0.436, Adjusted R2 5 0.389, p 5 .01.
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TABLE 2. Postoperative biochemical data (parathyroid hormone at a minimum of 3 months and corrected calcium at a minimum of 1 year), intraoperative localization findings, and histopathological dimensions of the adenoma. Postoperative Histological corrected Postoperative Actual adenoma diameter, calcium, 21 21 PTH, pmoll location mm mmoll
Case no.
RAP 1 RAP 2 RAP 3
4.4 4.7 33.8*
2.39 2.42 2.30
RAP 4 RAP 5 RAP 6 RAP 7 RAP 8 RAP 9 RAP 10 RAP 11 RAP 12 RAP 13 RAP 14 RAP 15
6.4 4.3 1.6 5.5 1.9 2.6 4.7 1.4 1.7 5.8 5.4 13.6*
2.39 2.38 2.40 2.43 2.42 2.39 2.43 2.37 2.46 2.43 2.33 2.53
Control 1 Control 2 Control 3 Control 4 Control 5 Control 6 Control 7 Control 8 Control 9 Control 10 Control 11 Control 12 Control 13 Control 14 Control 15
2.3 4.4 6.2 1.2 6.5 1.8 1.4 6.0 6.3 4.1 4.5 4.9 4.7 3.2 12.7†
2.21 2.39 2.45 2.45 2.39 2.34 2.34 2.40 2.40 2.33 2.55 2.32 2.27 2.47 2.59
Left inferior Right inferior 4-gland hyperplasia* Left inferior Right inferior Left inferior Right inferior Right superior Left inferior Left inferior Left inferior Right superior Right superior Right inferior 4-gland hyperplasia* Left superior Left inferior Left superior Right inferior Right inferior Right inferior Right superior Left superior Right superior Right inferior Left inferior Left inferior Left inferior Right superior Unknown†
15 20 15 18 16 30 22 30 13 20 15 30 28 25 29 20 8 16 12 14 12 22 20 28 19 22 10 22 30 8
Abbreviations: PTH, parathyroid hormone; RAP, robotic-assisted parathyroidectomy. * Corresponds to the 2 patients who underwent RAP who had persistent hyperparathyroidism because of 4-gland hyperplasia not detected on the initial localization imaging. Further surgery involving bilateral neck exploration cured both of these patients. † Corresponds to the 1 patient in the control group who had persistent hyperparathyroidism after focused lateral parathyroidectomy (FLP) but declined further investigation or treatment. Normal range: PTH 5 1.1–6.8 pmoll21; corrected calcium 5 2.15–2.60 mmoll21.
localized. RAP has been shown to be feasible and safe.5,17,18 To the best of our knowledge, this is the first study to compare RAP with another targeted approach. A learning curve was observed for RAP and this phenomenon is well-described in other surgical fields.20 RAP takes considerably longer than FLP even when the learning curve is accounted for. As with all appropriately performed parathyroidectomy techniques, blood loss was negligible. Recurrent laryngeal nerve identification, a key principle of parathyroid surgery, was easily achieved because of the magnified 3D visualization afforded by the dual-channel endoscope. There were no short-term complications, such as recurrent laryngeal nerve palsy, bleeding, or hypocalcemia. One wound infection did occur in the RAP group that resolved with oral antibiotics. Persistent PHPT occurred in both groups and is reported in E304
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FIGURE 3. Comparison of the 2 study groups in terms of scar satisfaction with visual analogue scale (VAS) in a postoperative period of 2 years. Bars represent SE for mean score. RAP, robotic-assisted parathyroidectomy; FLP, focused lateral parathyroidectomy. *p < .05; **p < .01.
approximately 5% of patients undergoing first-time surgery.21 Persistent hyperparathyroidism is a recognized complication of a focused approach without intraoperative PTH localization and not a reflection of the robotic technique per se.22 The high rate in this study is due to the small number of patients recruited and does not reflect our unit’s numbers. The data from our unit, which are prospectively entered in the national British Association of Endocrine and Thyroid Surgeons database, reveal a 4.2% rate (ie, below the national average). The 2 of 15 cases of persistent hyperparathyroidism were due to 4gland hyperplasia that was not evident from the initial preoperative localization imaging. Further surgery involving 4-gland exploration and subtotal (3 [1/2] gland) parathyroidectomy via a cervicotomy cured these patients. The lateral focused approach patient refused further surgery. This risk could be reduced using an intraoperative
FIGURE 4. Quality of life (QOL) recording with visual analogue scale (VAS) during the post\operative period in the roboticassisted parathyroidectomy (RAP) and focused lateral parathyroidectomy (FLP) groups. Bars represent SE for mean score.
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FIGURE 5. Comparison of the 2 study groups regarding changes in the quality of life (QOL) between the preoperative period and 12 months after surgery using visual analogue score (VAS). Bars represent 95% confidence interval for mean score.
PTH assay, which was not in routine use at the time of this study. Pain was significantly lower in the RAP group at 2 weeks compared to the FLP group. Although it is difficult to account for the exact reasons as to why this may be the case, it could be that the stretching and pulling required with the small neck incision leads to that “extra initial pain,” something that is not required with the robotic approach. Moreover, with the infraclavicular approach, no insufflation is required and the area of subcutaneous dissection required to raise the flap is smaller than that required when using a transaxillary approach. Interestingly, similar findings have also been reported in the literature for robotic transaxillary thyroidectomy, with patients undergoing the robotic procedure complaining of less pain than those undergoing conventional open thyroidectomy.23 Global QOL is known to improve after parathyroidectomy.24 The cumulative EuroQOL-5D questionnaire score showed a return to normal levels by 2 weeks. There was no significant difference between the 2 groups. Satisfaction with scar cosmesis was higher after RAP compared with FLP at 2 weeks, 3 months, 6 months, 12 months, and 24 months postoperatively. The difference was not statistically significant after 6 months. Increased satisfaction with scar cosmesis seems to be the primary clinical advantage of RAP (see Figure 6).5,17,18 The approach could, therefore, be justified in a subset of patients with a propensity toward hypertrophic or keloid scarring and those patients where the cosmetic impact of a neck scar carries significant social stigma.25,26
However, the findings in this study showed no statistically significant difference in scar cosmesis between the groups beyond 6 months. Patient satisfaction with scar cosmesis after FLP is reportedly high because the neck scar is small and usually heals well, although these studies rarely report outcomes beyond 6 months.26 In a retrospective study of 691 patients, Linos et al27 concluded that a smaller neck incision was not associated with greater patient satisfaction. Long-term evaluation with more patients assigned to each cohort is therefore necessary to corroborate the findings of this study. The importance of careful patient selection cannot be overemphasized. One patient (RAP case 8) required conversion to an open approach because of suboptimal surgical access owing to the patient’s large body habitus (BMI 5 33.4 kg22). Obese patients are not good candidates for this approach because adequate exposure is more challenging.28 In this series, a short neck, a BMI >33 kgm22, and a retroclavicular location increased the console time. Cost is another important issue. This is high because of the initial outlay ($1.4 million), subsequent maintenance ($150,000 per annum) and consumable ($1700 per case) costs, and the significantly longer operating time incurred.26,29 It may be that if patients express a preference for the extracervical approach, they will have to fund such surgery.28 Like all studies, this study had certain limitations. It was not randomized, included a relatively small sample (n 5 30), and selection bias must be acknowledged as a potential confounding factor. Nevertheless, careful patient selection is important in surgery to ensure a successful outcome. Although a relatively small number of patients were recruited, the objective of this pilot study was to compare the technique of RAP with FLP in order to create the foundation for a larger definitive clinical trial. A power calculation was therefore not performed. Lack of randomization constitutes a limitation of surgical research in general.29 To minimize this bias, both groups were matched in terms of mean BMI, age, sex, and pathology.
FIGURE 6. A close-up photograph of a patient 6 months after right robotic-assisted parathyroidectomy (RAP).
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There is a potential “performance” bias because 2 surgeons performed FLP, although this was minimized by using a standardized technique and both surgeons had sufficient experience to surpass the learning curve. Despite its limitations, this study also possesses several strengths. There are only a handful of case series in the literature evaluating RAP outcomes.5,17,18 Moreover, few studies have prospectively evaluated the outcome of targeted parathyroidectomy beyond 12 months.3 Long-term follow-up is important because of the natural history of wound healing. A similar study used heterogeneous cohorts consisting of both thyroidectomy and parathyroidectomy patients.26 In contrast, this study includes homogeneous groups with matched patients. The data were collected prospectively and assessed both surgical and patient-related outcomes. The VAS used to report scar cosmesis is validated for use in parathyroid surgery and reliably discriminates between different types of scar quality.30 Outcome measures for pain used a VAS, which is sensitive enough to detect clinically relevant changes in pain intensity over time.31 The mean clinical and biochemical follow-up period in this study was over 2 years, which is considerably longer than other studies.26,32 It is important to appreciate that RAP is not for every patient, surgeon, or hospital. Only those who have undergone necessary training, proctoring, and licensure should perform robotic surgery. Sufficient experience of parathyroid surgery is essential. The nursing team must be trained and institutions must have an appropriate sized operating room and the necessary technical support. The introduction of new robotic systems (eg, Amadeus Robotic Surgical System; Titan Medical, Toronto, Ontario, Canada, and Flex System, Medrobotics, Raynham, MA) will create much needed competition. The existing climate is a monopoly limited by high cost and the need for expensive training.33 It remains to be seen whether these issues preclude its widespread adoption. In conclusion, RAP offers a viable but expensive alternative to other forms of targeted parathyroidectomy in patients who want to avoid a neck scar. This study showed superior cosmesis for RAP but only up to 6 months. Larger, definitive studies are currently in progress to evaluate long-term cosmetic satisfaction. At present, RAP occupies a niche role and can only be justified in patients who have cultural or biological drivers to avoid a neck scar.
Acknowledgments The authors wish to acknowledge the invaluable input of Mrs. Shirley Martin, clinical robotic nurse specialist, and Mr. James Budge, medical student for their assistance in the preparation of the manuscript.
REFERENCES 1. Melton LJ III. The epidemiology of primary hyperparathyroidism in North America. J Bone Miner Res 2002;17 Suppl 2:N12–N17. 2. Pallan S, Rahman MO, Khan AA. Diagnosis and management of primary hyperparathyroidism. BMJ 2012;344:e1013. 3. Venkat R, Kouniavsky G, Tufano RP, Schneider EB, Dackiw AP, Zeiger MA. Long-term outcome in patients with primary hyperparathyroidism who underwent minimally invasive parathyroidectomy. World J Surg 2012; 36:55–60.
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4. Delbridge LW, Palazzo FF. First parathyroid surgeon: Sir John Bland–Sutton and the parathyroids. ANZ J Surg 2007;77:1058–1061. 5. Tolley N, Arora A, Palazzo F, et al. Robotic-assisted parathyroidectomy: a feasibility study. Otolaryngol Head Neck Surg 2011;144:859–866. 6. Palazzo FF, Delbridge LW. Minimal-access/minimally invasive parathyroidectomy for primary hyperparathyroidism. Surg Clin North Am 2004;84: 717–734. 7. Agarwal G, Barraclough BH, Robinson BG, Reeve TS, Delbridge LW. Minimally invasive parathyroidectomy using the ‘focused’ lateral approach. I. Results of the first 100 consecutive cases. ANZ J Surg 2002;72: 100–104. 8. Henry JF, Sebag F, Ippolito G. Endoscopic parathyroidectomy through a lateral approach [in French]. J Chir (Paris) 2008;145:470–474. 9. Miccoli P, Berti P, Materazzi G, Donatini G. Minimally invasive video assisted parathyroidectomy (MIVAP). Eur J Surg Oncol 2003;29:188–190. 10. Miccoli P, Bendinelli C, Berti P, Vignali E, Pinchera A, Marcocci C. Video-assisted versus conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study. Surgery 1999;126:1117– 1121; discussion 1121–1122. 11. Ikeda Y, Takami H. Endoscopic parathyroidectomy. Biomed Pharmacother 2000;54 Suppl 1:52s–56s. 12. Kang J, Fan Y, Guo B, Wu B, Zheng Q. Trans-areola single-site endoscopic parathyroidectomy: report of one case. Surg Innov 2013;20: NP16–NP20. 13. Lee KE, Kim HY, Park WS, et al. Postauricular and axillary approach endoscopic neck surgery: a new technique. World J Surg 2009;33:767–772. 14. Chung YS, Choe JH, Kang KH, et al. Endoscopic thyroidectomy for thyroid malignancies: comparison with conventional open thyroidectomy. World J Surg 2007;31:2302–2306; discussion 2307–2308. 15. Ewing DR, Pigazzi A, Wang Y, Ballantyne GH. Robots in the operating room–the history. Semin Laparosc Surg 2004;11:63–71. 16. Moorthy K, Munz Y, Dosis A, et al. Dexterity enhancement with robotic surgery. Surg Endosc 2004;18:790–795. 17. Karagkounis G, Uzun DD, Mason DP, Murthy SC, Berber E. Robotic surgery for primary hyperparathyroidism. Surg Endosc 2014;28:2702–2707. 18. Noureldine SI, Lewing N, Tufano RP, Kandil E. The role of the roboticassisted transaxillary gasless approach for the removal of parathyroid adenomas. ORL J Otorhinolaryngol Relat Spec 2014;76:19–24. 19. Agarwal G, Barraclough BH, Reeve TS, Delbridge LW. Minimally invasive parathyroidectomy using the ‘focused’ lateral approach. II. Surgical technique. ANZ J Surg 2002;72:147–151. 20. Kaul S, Shah NL, Menon M. Learning curve using robotic surgery. Curr Urol Rep 2006;7:125–129. 21. The British Association of Endocrine & Thyroid Surgeons, Fourth National Audit Report; 2012. Available at: http://www.baets.org.uk/wp-content/ uploads/2013/05/4th-National-Audit.pdf. Accessed June 1, 2014. 22. Miccoli P, Berti P, Materazzi G, Massi M, Picone A, Minuto MN. Results of video-assisted parathyroidectomy: single institution’s six-year experience. World J Surg 2004;28:1216–1218. 23. Lee J, Kwon IS, Bae EH, Chung WY. Comparative analysis of oncological outcomes and quality of life after robotic versus conventional open thyroidectomy with modified radical neck dissection in patients with papillary thyroid carcinoma and lateral neck node metastases. J Clin Endocrinol Metab 2013;98:2701–2708. 24. Weber T, Keller M, Hense I, et al. Effect of parathyroidectomy on quality of life and neuropsychological symptoms in primary hyperparathyroidism. World J Surg 2007;31:1202–1209. 25. Allah KC, Yeo S, Kossoko H, Assi Dje` Bi Dje` V, Richard Kadio M. Keloid scars on black skin: myth or reality [in French]. Ann Chir Plast Esthet 2013;58:115–122. 26. Foley CS, Agcaoglu O, Siperstein AE, Berber E. Robotic transaxillary endocrine surgery: a comparison with conventional open technique. Surg Endosc 2012;26:2259–2266. 27. Linos D, Economopoulos KP, Kiriakopoulos A, Linos E, Petralias A. Scar perceptions after thyroid and parathyroid surgery: comparison of minimal and conventional approaches. Surgery 2013;153:400–407. 28. Landry CS, Grubbs EG, Morris GS, et al. Robot assisted transaxillary surgery (RATS) for the removal of thyroid and parathyroid glands. Surgery 2011;149:549–555. 29. Garas G, Ibrahim A, Ashrafian H, et al. Evidence-based surgery: barriers, solutions, and the role of evidence synthesis. World J Surg 2012;36: 1723–1731. 30. Duncan JA, Bond JS, Mason T, et al. Visual analogue scale scoring and ranking: a suitable and sensitive method for assessing scar quality? Plast Reconstr Surg 2006;118:909–918. 31. Crossley KM, Bennell KL, Cowan SM, Green S. Analysis of outcome measures for persons with patellofemoral pain: which are reliable and valid? Arch Phys Med Rehabil 2004;85:815–822. 32. Fraker DL, Harsono H, Lewis R. Minimally invasive parathyroidectomy: benefits and requirements of localization, diagnosis, and intraoperative PTH monitoring. Long-term results. World J Surg 2009;33:2256–2265. 33. Trehan A, Dunn TJ. The robotic surgery monopoly is a poor deal. BMJ 2013;347:f7470.
Long-term prospective evaluation comparing robotic parathyroidectomy with minimally invasive open parathyroidectomy for primary hyperparathyroidism Neil Tolley, MD, FRCS, DLO,1 George Garas, MRCS, DOHNS,1 Fausto Palazzo, MS, FRCS,2 Alexa Prichard, MBBS,1 Konstantinos Chaidas, MD, PhD,1 Jeremy Cox, MD, FRCP,3 Ara Darzi, KBE, MD, FRCS,4 Asit Arora, MRCS, DOHNS1* 1
Department of Otorhinolaryngology and Head & Neck Surgery, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom, 2Department of Endocrine and Thyroid Surgery, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom, 3Department of Endocrinology, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom, 4Department of Surgery and Cancer, Imperial College London, St. Mary’s Hospital Campus, London, United Kingdom.
Accepted 18 December 2014 Published online 26 June 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23990
ABSTRACT: Background. Targeted parathyroidectomy is a popular technique for localized pathology. No single technique is established as superior. The purpose of this study was to compare robotic-assisted parathyroidectomy (RAP) with the most common approach. Methods. This was a prospective, nonrandomized study. Fifteen consecutive patients who underwent RAP were compared to 15 matched controls undergoing focused lateral parathyroidectomy (FLP). Results. Biochemical cure occurred in 29 of 30 patients (97%). No major complications occurred, although there was 1 robotic conversion. RAP demonstrated a significant time reduction (R2 5 0.436; p 5 .01) but took much longer to perform than FLP (119 minutes vs 34 minutes; p 5 .001).
INTRODUCTION Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder after diabetes mellitus and osteoporosis.1 Although the exact incidence is unknown, its prevalence is estimated at between 1 to 4 of 1000 with a 3:1 female to male ratio.2 Approximately 80% of PHPT are due to a solitary parathyroid adenoma. Multigland disease in the form of multiple adenomas or parathyroid hyperplasia accounts for the remaining cases.2,3 Surgery remains the only definitive cure for PHPT and this has changed considerably since Felix Mandel performed the first successful parathyroidectomy in 1925.3,4 Over the decades, the surgical approach evolved into a standardized exploration of the neck via a “collar” incision. The objective has been to identify all the parathyroid glands, leaving the normal glands in situ and
*Corresponding author: A. Arora, Department of Otorhinolaryngology and Head & Neck Surgery, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, Praed Street, London, United Kingdom, W2 1NY. E-mail: [email protected] The preliminary findings of this study were presented at the 2011 British Association of Endocrine & Thyroid Surgeons annual meeting; September 22–23, 2011, Poitiers, France, where it was awarded the best poster presentation prize and also as a podium presentation at both the 2012 American Academy of Otolaryngology-Head and Neck Surgery & OTO EXPO, September 9–12, 2012, Washington, DC; and 20th International Federation of Oto-Rhino-Laryngological Societies World Congress, June 1–5, 2013, Seoul, Korea.
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RAP was associated with less initial postoperative pain (p 5 .036) and higher satisfaction with scar cosmesis (p 5 .002) until 6 months. Quality of life (QOL) improved in both groups (p 5 .007). Conclusion. RAP provides superior early cosmesis with equivalent global health improvement compared to FLP. The high cost and learning curve may preclude widespread adoption. Further evaluation is necessary to C 2015 Wiley establish its clinical efficacy regarding scar cosmesis. V Periodicals, Inc. Head Neck 38: E300–E7, 2016
KEY WORDS: robotic, surgery, hyperparathyroidism, cosmesis, outcomes
removing the diseased gland or glands. In the past 3 decades, there has been a significant improvement in the accuracy of preoperative localization studies. The reliable identification of a parathyroid adenoma has created the right background for a targeted surgical approach making targeted parathyroidectomy a well-established approach in the 65% of patients with localized single-gland pathology.5 A variety of targeted, minimal access techniques have been described. Despite numerous options, no single technique is established as demonstrably superior.6 However, the focused lateral parathyroidectomy (FLP) is the most widely adopted because of its simplicity and the lack of requirement for any additional equipment while offering cure and complication rates equivalent to both the conventional and other minimal access techniques.7–9 Advantages over the former include reduced operating times, smaller scars, shorter hospital stays, and less postoperative analgesic requirement.10 More recently, the endoscopic “scar-less in the neck” approach has been described. Studies suggest that avoiding a neck scar improves patient satisfaction.11–13 However, this approach has not been widely adopted because of limitations associated with the endoscopic platform. These include suboptimal depth perception because of a 2D view and restricted instrument movement because of the narrow working space.14 The da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced to address these limitations.15
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The dual-channel endoscope permits image magnification with the additional benefit of a 3D view of the operative field and superior depth perception compared to conventional endoscopy. The console surgeon controls 5 mm “wristed” instruments. This allows precise tissue manipulation within the confined space of the anterior neck compartment. The tremor filtering and motion scaling features enhance surgical dexterity.16 Feasibility studies of robotic-assisted parathyroidectomy (RAP) using an infraclavicular5 or transaxillary approach have been reported.17,18 However, the clinical efficacy of this approach compared to conventional targeted parathyroidectomy is not established. Therefore, the purpose of this study was to compare the outcome of RAP and FLP. The objective was to establish whether RAP conferred any additional benefit.
MATERIALS AND METHODS Ethical approval The study received favorable approval from the National Health Service Health Research Authority (National Research Ethics Service Committee London, Protocol Reference Number: 08/H0721/97).
Study design A prospective comparative study was conducted. Patients were recruited between April 2009 and December 2010 from the Departments of Otorhinolaryngology and Head & Neck Surgery (St. Mary’s Hospital Campus) and Endocrine and Thyroid Surgery (Hammersmith Hospital Campus), Imperial College Healthcare NHS Trust, London, UK. The unit does approximately 200 parathyroidectomy cases per annum and all cases are entered in the national British Association of Endocrine and Thyroid Surgeons database. Fifteen unselected consecutive FLPs and 15 consecutive RAPs were compared. The selection criteria were the same for both patients who underwent FLP and RAP, as described below. Both approaches were offered to all patients who met those criteria and the first 15 patients that opted for FLP were compared with the first 15 that opted for RAP. This was done to minimize differences between the groups (eg, age, body mass index [BMI], and localization) other than the approach used, in view of the lack of randomization.
Selection criteria Criteria included a biochemical diagnosis of PHPT because of a single parathyroid adenoma on imaging. Triple modality concordant localization using ultrasonography, sestamibi, and single-photon emission CT was a prerequisite to be considered for study inclusion. The diagnosis required an albumin-adjusted serum total calcium >2.60 mmoll21 on repeat samples, with an elevated parathyroid hormone (PTH) of >6.8 pmoll21 taken concurrently. Interfering medications, such as thiazide diuretics or lithium, were discontinued before testing. Familial hypocalciuric hypercalcemia was excluded by measuring 24-hour urine calcium levels. All patients had a 24-hour urine calcium >5 mmol, and/or a 24-hour urine calcium/creatinine clearance ratio >0.01. Patients with a family history of PHPT or associated endocrine condi-
tions, evidence of thyroiditis or bulky thyroid disease, and/or previous neck surgery or irradiation were not eligible for inclusion in this study.
Patients Thirty patients were recruited. The patient demographics, BMI, biochemical data, and radiological localization of the parathyroid adenoma are summarized in Table 1.
Treatment allocation The selection of a robotic versus a conventional approach was based upon patient preference (see Study design). Both approaches were offered to all patients. All RAP cases were performed by the same console and bedside surgeon (N.S.T. and A.A., respectively). FLP was performed by 1 of 2 senior surgeons (N.S.T. and F.P.) scrubbed in with an assistant surgeon (A.A.). Both senior surgeons were experienced with FLP each having performed over 300 cases.
Surgical technique Robotic-assisted parathyroidectomy. The surgical approach has been described in detail in a previous publication.5 The robotic arm is maintained in the neutral position. An infraclavicular incision is made ipsilateral to the adenoma. The exact position of the incision depends on body habitus and patient preference. It is drawn with the patient awake to ensure it is concealed even when wearing low-cut tops. Dissection proceeds through the natural dehiscence between the sternal and clavicular insertions to expose the internal jugular vein, common carotid artery, and ipsilateral omohyoid and sternohyoid muscles. A self-retaining (Chung or Imperial) retractor is used to maintain sufficient working space and 2 additional 5-mm trocar incisions are made in the anterior axillary line. Again, the exact positions vary. Most commonly, the first stab incision is made at the superior part of that line at the level of the pectoralis major tendon with the lower being made about 4 cm below. If body habitus permits, the 5 mm inferior trocar is inserted via an ipsilateral periareolar incision instead (see Figure 1). The remaining dissection is performed with the da Vinci robot. Drains are not inserted. Focused lateral parathyroidectomy. The technique described by Agarwal et al19 was used. An ipsilateral mini cervicotomy is made over the anterior border of the sternocleidomastoid muscle at a level depending on the position of the adenoma. The subplatysmal flaps are raised via sharp and blunt dissection. Dissection is performed lateral to the strap muscles to obtain access to the posterolateral thyroid lobe. After excision of the parathyroid adenoma and hemostasis, closure is achieved in a 2-layer format. No drains are used.
Outcome measures and follow-up The success of the procedure was determined biochemically with normalization of the albumin-adjusted serum total calcium and PTH levels after surgery and by histopathological confirmation of the presence of hypercellular parathyroid tissue in the excised lesion. HEAD & NECK—DOI 10.1002/HED
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TABLE 1. Patient demographics, body mass index, preoperative biochemical data, and radiological localization of the parathyroid adenoma.
Case
RAP 1 RAP 2 RAP 3 RAP 4 RAP 5 RAP 6 RAP 7 RAP 8 RAP 9 RAP 10 RAP 11 RAP 12 RAP 13 RAP 14 RAP 15 Control 1 Control 2 Control 3 Control 4 Control 5 Control 6 Control 7 Control 8 Control 9 Control 10 Control 11 Control 12 Control 13 Control 14 Control 15
Sex
Age, y
BMI, kg22
Ethnic origin
Preoperative PTH, pmoll21
Preoperative corrected calcium, mmoll21
Localization
Female Male Female Female Female Female Male Male Female Female Female Female Female Female Female Male Female Female Female Female Female Female Male Female Female Female Female Female Female Female
72 49 49 70 46 68 79 50 58 58 48 51 75 42 67 54 46 45 46 70 70 63 75 50 38 46 58 63 57 74
24.8 26.1 27.4 25.3 28.5 27.7 22.5 33.4 22.8 23.8 27.9 21.5 26.6 27.5 28.9 25.9 28.9 31.8 23.4 28.7 27.2 25.9 28.1 25.4 26.9 27.8 24.9 31.7 26.7 24.6
White Asian White Afro-Caribbean Afro-Caribbean White Afro-Caribbean White White White White White White White Afro-Caribbean White White White White Asian White Asian Afro-Caribbean White White Asian White Asian White Asian
12.5 15.7 34.0 15.6 16.0 11.4 27.9 21.2 15.3 15.3 30.7 11.4 19.7 14.2 17.9 13.0 21.5 13.2 22.9 11.7 14.6 7.1 18.8 26.4 14.8 26.1 63.3 26.1 14.2 16.0
2.61 2.62 2.96 2.66 3.07 2.80 2.95 2.99 2.67 2.85 2.75 2.61 2.78 2.66 2.75 2.61 2.76 2.70 2.68 2.70 2.78 2.81 3.01 2.93 2.71 2.66 3.20 2.63 2.91 2.80
Left inferior Right inferior Left inferior Left inferior Right inferior Left inferior Right inferior Right superior Left inferior Left inferior Left inferior Right superior Right superior Right inferior Left inferior Left superior Left inferior Left superior Right inferior Right inferior Right inferior Right superior Left superior Right superior Right inferior Left inferior Left inferior Left inferior Right superior Right superior
Abbreviations: BMI, body mass index; PTH, parathyroid hormone; RAP, robotic-assisted parathyroidectomy. Normal range: PTH 5 1.1–6.8 pmoll21; corrected calcium 5 2.15–2.60 mmoll21.
Patient-reported outcome measures included prospective assessment of scar cosmesis, pain, voice disability, and global health using validated assessment tools. Scar cosmesis was assessed using a 0 to 100 visual analog scale (VAS), in which 100 represented “completely satisfied.” Pain was assessed using a 0 to 100 VAS, in which 100 represented “worst imaginable pain.” The pain management was the same in both groups. All patients were given regular oral acetaminophen 1 g every 6 hours and ibuprofen 400 mg every 8 hours. Voice satisfaction was rated using the Voice Handicap Index-2 questionnaire. Moreover, all patients had preoperative and postoperative laryngoscopy. Global quality of life (QOL) was assessed using the EuroQOL-5D questionnaire assessment tool that comprises a descriptive system and EuroQOL-visual analog scale. The former comprises 5 dimensions: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each is self-rated as 1 5 no problems, 2 5 some problems, and 3 5 severe problems. The EuroQOL-visual analog scale is a 0 to 100 scale in which 100 represented “best imaginable health state.”
Statistical analysis The 2 groups were compared regarding the patients’ characteristics, intraoperative findings, and postoperative results using chi-square test (categorical variables) or E302
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Mann–Whitney and Wilcoxon test (continuous variables). A logarithmic regression model was used to evaluate the robotic learning curve for the time taken to perform the robotic procedure. The comparisons were performed using SPSS software version 21.0 (SPSS, Chicago, IL). Statistical significance was accepted when p < .05.
RESULTS Patients The RAP and FLP groups were matched in terms of age (58.8 6 12.0 years vs 57.0 6 11.8 years, respectively; p 5 .618), sex (3 of 15 men vs 2 of 15 men, respectively; p 5 .624), race, BMI (26.3 6 3.0 kg22 vs 27.2 6 2.4 kg22, respectively; p 5 .436), size of lesion (21.7 6 6.4 mm vs 17.5 6 6.8 mm, respectively; p 5 .118), and comorbidity.
Operative data The mean incision length for the robotic approach was 3.9 cm, whereas for the open approach it was 3.6 cm (p 5 .293). The parathyroid adenoma was successfully identified and removed in all cases. Pathological evaluation of the excised specimen confirmed hypercellular parathyroid tissue. The mean blood loss was 9.9 6 3.9 mL in the robotic group and 11.6 6 2.6 mL in the conventional group (p 5 .056). One RAP case was converted to an open procedure because
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and PTH normalized postoperatively in 14 patients. One patient had persistent hyperparathyroidism but declined further investigation or treatment. The remaining 29 patients were normocalcemic at latest follow-up (minimum 12-month timeframe after surgery).
Postoperative complications One postoperative complication occurred in the robotic cohort (RAP case 11). A superficial wound infection was treated with oral antibiotics (co-amoxiclav) with no adverse clinical outcome.
Patient-reported outcome measures
FIGURE 1. Incisions for right robotic-assisted parathyroidectomy marked in red. All incisions are ipsilateral. Exact positions can vary as they depend on body habitus and patient preference. The infraclavicular incision is drawn with the patient awake to ensure it is concealed even when wearing low-cut tops. The first stab incision is made at the superior part of the anterior axillary line at the level of the pectoralis major tendon with the lower made about 4 cm below. If body habitus permits, the 5 mm inferior trocar is inserted via an ipsilateral periareolar incision instead, as indicated.
Patients were followed up after surgery for a mean period of 24.8 6 14 months. Postoperative pain at 2 weeks was significantly less for patients in the RAP group compared to those in the FLP group (6.43 6 9.7 vs 24.33 6 24.1, respectively; p 5 .036). Regarding scar cosmesis, the mean VAS score was significantly higher for the robotic group compared to the FLP group at 3 months (91.3 6 9.2 vs 65.7 6 19.2, respectively; p 5 .005) and 6 months (92.8 6 7.7 vs 70.7 6 19.2, respectively; p 5 .002) after surgery, but not at 12 months (94.3 6 5.8 vs 80.4 6 28.4, respectively; p 5 .523) and 24 months (95 6 5.0 vs 81.7 6 35.3, respectively; p 5 .849; see Figure 3). There was no difference in global QOL between the groups (see Figure 4), which significantly improved up to 1 year after surgery in both groups (p 5 .007 for the RAP group and p 5 .043 for the FLP group; see Figure 5). All patients had preoperative and postoperative laryngoscopy. Postoperative laryngoscopy was performed on the first postoperative day and confirmed normal vocal cord mobility in all patients (n 5 30). Significant voice disability was not reported after surgery using the Voice Handicap Index-2 questionnaire. All patients were discharged within 24 hours.
DISCUSSION Targeted parathyroidectomy is a popular surgical option for PHPT when the abnormal parathyroid gland has been of suboptimal surgical access owing to the patient’s large body habitus (RAP case #8; BMI 5 33.4 kg22). The mean operative time was significantly higher for RAP compared to FLP (119 minutes vs 34 minutes, respectively; p 5 .001). In the robotic cohort, a clear learning curve was demonstrated (see Figure 2). Logarithmic regression analysis (excluding the 1 conversion) revealed a progressive reduction in operating time from 190 minutes to 57 minutes (R2 5 0.436; p 5 .01).
Biochemistry The postoperative biochemical data, intraoperative localization findings, and histopathological dimensions are shown in Table 2. The mean biochemical follow-up was 27 6 12.2 months. There was no difference in the cure rate between groups (p 5 .543). In the robotic cohort, initial normalization of PTH and adjusted serum calcium levels occurred in 13 patients. The remaining 2 patients had persistent hyperparathyroidism because of 4-gland hyperplasia not detected on the initial localization imaging. Further surgery involving bilateral neck exploration cured them. In the FLP group, adjusted serum calcium
FIGURE 2. Learning curve regarding operative time (in minutes) for robotic-assisted parathyroidectomy (RAP). Case #8, which necessitated conversion to open surgery (body mass index [BMI] 5 33.4) was excluded from the analysis. y 5 180.9435 1 (233.5482 * log(x)) R 5 0.661, R2 5 0.436, Adjusted R2 5 0.389, p 5 .01.
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TABLE 2. Postoperative biochemical data (parathyroid hormone at a minimum of 3 months and corrected calcium at a minimum of 1 year), intraoperative localization findings, and histopathological dimensions of the adenoma. Postoperative Histological corrected Postoperative Actual adenoma diameter, calcium, 21 21 PTH, pmoll location mm mmoll
Case no.
RAP 1 RAP 2 RAP 3
4.4 4.7 33.8*
2.39 2.42 2.30
RAP 4 RAP 5 RAP 6 RAP 7 RAP 8 RAP 9 RAP 10 RAP 11 RAP 12 RAP 13 RAP 14 RAP 15
6.4 4.3 1.6 5.5 1.9 2.6 4.7 1.4 1.7 5.8 5.4 13.6*
2.39 2.38 2.40 2.43 2.42 2.39 2.43 2.37 2.46 2.43 2.33 2.53
Control 1 Control 2 Control 3 Control 4 Control 5 Control 6 Control 7 Control 8 Control 9 Control 10 Control 11 Control 12 Control 13 Control 14 Control 15
2.3 4.4 6.2 1.2 6.5 1.8 1.4 6.0 6.3 4.1 4.5 4.9 4.7 3.2 12.7†
2.21 2.39 2.45 2.45 2.39 2.34 2.34 2.40 2.40 2.33 2.55 2.32 2.27 2.47 2.59
Left inferior Right inferior 4-gland hyperplasia* Left inferior Right inferior Left inferior Right inferior Right superior Left inferior Left inferior Left inferior Right superior Right superior Right inferior 4-gland hyperplasia* Left superior Left inferior Left superior Right inferior Right inferior Right inferior Right superior Left superior Right superior Right inferior Left inferior Left inferior Left inferior Right superior Unknown†
15 20 15 18 16 30 22 30 13 20 15 30 28 25 29 20 8 16 12 14 12 22 20 28 19 22 10 22 30 8
Abbreviations: PTH, parathyroid hormone; RAP, robotic-assisted parathyroidectomy. * Corresponds to the 2 patients who underwent RAP who had persistent hyperparathyroidism because of 4-gland hyperplasia not detected on the initial localization imaging. Further surgery involving bilateral neck exploration cured both of these patients. † Corresponds to the 1 patient in the control group who had persistent hyperparathyroidism after focused lateral parathyroidectomy (FLP) but declined further investigation or treatment. Normal range: PTH 5 1.1–6.8 pmoll21; corrected calcium 5 2.15–2.60 mmoll21.
localized. RAP has been shown to be feasible and safe.5,17,18 To the best of our knowledge, this is the first study to compare RAP with another targeted approach. A learning curve was observed for RAP and this phenomenon is well-described in other surgical fields.20 RAP takes considerably longer than FLP even when the learning curve is accounted for. As with all appropriately performed parathyroidectomy techniques, blood loss was negligible. Recurrent laryngeal nerve identification, a key principle of parathyroid surgery, was easily achieved because of the magnified 3D visualization afforded by the dual-channel endoscope. There were no short-term complications, such as recurrent laryngeal nerve palsy, bleeding, or hypocalcemia. One wound infection did occur in the RAP group that resolved with oral antibiotics. Persistent PHPT occurred in both groups and is reported in E304
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FIGURE 3. Comparison of the 2 study groups in terms of scar satisfaction with visual analogue scale (VAS) in a postoperative period of 2 years. Bars represent SE for mean score. RAP, robotic-assisted parathyroidectomy; FLP, focused lateral parathyroidectomy. *p < .05; **p < .01.
approximately 5% of patients undergoing first-time surgery.21 Persistent hyperparathyroidism is a recognized complication of a focused approach without intraoperative PTH localization and not a reflection of the robotic technique per se.22 The high rate in this study is due to the small number of patients recruited and does not reflect our unit’s numbers. The data from our unit, which are prospectively entered in the national British Association of Endocrine and Thyroid Surgeons database, reveal a 4.2% rate (ie, below the national average). The 2 of 15 cases of persistent hyperparathyroidism were due to 4gland hyperplasia that was not evident from the initial preoperative localization imaging. Further surgery involving 4-gland exploration and subtotal (3 [1/2] gland) parathyroidectomy via a cervicotomy cured these patients. The lateral focused approach patient refused further surgery. This risk could be reduced using an intraoperative
FIGURE 4. Quality of life (QOL) recording with visual analogue scale (VAS) during the post\operative period in the roboticassisted parathyroidectomy (RAP) and focused lateral parathyroidectomy (FLP) groups. Bars represent SE for mean score.
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FIGURE 5. Comparison of the 2 study groups regarding changes in the quality of life (QOL) between the preoperative period and 12 months after surgery using visual analogue score (VAS). Bars represent 95% confidence interval for mean score.
PTH assay, which was not in routine use at the time of this study. Pain was significantly lower in the RAP group at 2 weeks compared to the FLP group. Although it is difficult to account for the exact reasons as to why this may be the case, it could be that the stretching and pulling required with the small neck incision leads to that “extra initial pain,” something that is not required with the robotic approach. Moreover, with the infraclavicular approach, no insufflation is required and the area of subcutaneous dissection required to raise the flap is smaller than that required when using a transaxillary approach. Interestingly, similar findings have also been reported in the literature for robotic transaxillary thyroidectomy, with patients undergoing the robotic procedure complaining of less pain than those undergoing conventional open thyroidectomy.23 Global QOL is known to improve after parathyroidectomy.24 The cumulative EuroQOL-5D questionnaire score showed a return to normal levels by 2 weeks. There was no significant difference between the 2 groups. Satisfaction with scar cosmesis was higher after RAP compared with FLP at 2 weeks, 3 months, 6 months, 12 months, and 24 months postoperatively. The difference was not statistically significant after 6 months. Increased satisfaction with scar cosmesis seems to be the primary clinical advantage of RAP (see Figure 6).5,17,18 The approach could, therefore, be justified in a subset of patients with a propensity toward hypertrophic or keloid scarring and those patients where the cosmetic impact of a neck scar carries significant social stigma.25,26
However, the findings in this study showed no statistically significant difference in scar cosmesis between the groups beyond 6 months. Patient satisfaction with scar cosmesis after FLP is reportedly high because the neck scar is small and usually heals well, although these studies rarely report outcomes beyond 6 months.26 In a retrospective study of 691 patients, Linos et al27 concluded that a smaller neck incision was not associated with greater patient satisfaction. Long-term evaluation with more patients assigned to each cohort is therefore necessary to corroborate the findings of this study. The importance of careful patient selection cannot be overemphasized. One patient (RAP case 8) required conversion to an open approach because of suboptimal surgical access owing to the patient’s large body habitus (BMI 5 33.4 kg22). Obese patients are not good candidates for this approach because adequate exposure is more challenging.28 In this series, a short neck, a BMI >33 kgm22, and a retroclavicular location increased the console time. Cost is another important issue. This is high because of the initial outlay ($1.4 million), subsequent maintenance ($150,000 per annum) and consumable ($1700 per case) costs, and the significantly longer operating time incurred.26,29 It may be that if patients express a preference for the extracervical approach, they will have to fund such surgery.28 Like all studies, this study had certain limitations. It was not randomized, included a relatively small sample (n 5 30), and selection bias must be acknowledged as a potential confounding factor. Nevertheless, careful patient selection is important in surgery to ensure a successful outcome. Although a relatively small number of patients were recruited, the objective of this pilot study was to compare the technique of RAP with FLP in order to create the foundation for a larger definitive clinical trial. A power calculation was therefore not performed. Lack of randomization constitutes a limitation of surgical research in general.29 To minimize this bias, both groups were matched in terms of mean BMI, age, sex, and pathology.
FIGURE 6. A close-up photograph of a patient 6 months after right robotic-assisted parathyroidectomy (RAP).
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There is a potential “performance” bias because 2 surgeons performed FLP, although this was minimized by using a standardized technique and both surgeons had sufficient experience to surpass the learning curve. Despite its limitations, this study also possesses several strengths. There are only a handful of case series in the literature evaluating RAP outcomes.5,17,18 Moreover, few studies have prospectively evaluated the outcome of targeted parathyroidectomy beyond 12 months.3 Long-term follow-up is important because of the natural history of wound healing. A similar study used heterogeneous cohorts consisting of both thyroidectomy and parathyroidectomy patients.26 In contrast, this study includes homogeneous groups with matched patients. The data were collected prospectively and assessed both surgical and patient-related outcomes. The VAS used to report scar cosmesis is validated for use in parathyroid surgery and reliably discriminates between different types of scar quality.30 Outcome measures for pain used a VAS, which is sensitive enough to detect clinically relevant changes in pain intensity over time.31 The mean clinical and biochemical follow-up period in this study was over 2 years, which is considerably longer than other studies.26,32 It is important to appreciate that RAP is not for every patient, surgeon, or hospital. Only those who have undergone necessary training, proctoring, and licensure should perform robotic surgery. Sufficient experience of parathyroid surgery is essential. The nursing team must be trained and institutions must have an appropriate sized operating room and the necessary technical support. The introduction of new robotic systems (eg, Amadeus Robotic Surgical System; Titan Medical, Toronto, Ontario, Canada, and Flex System, Medrobotics, Raynham, MA) will create much needed competition. The existing climate is a monopoly limited by high cost and the need for expensive training.33 It remains to be seen whether these issues preclude its widespread adoption. In conclusion, RAP offers a viable but expensive alternative to other forms of targeted parathyroidectomy in patients who want to avoid a neck scar. This study showed superior cosmesis for RAP but only up to 6 months. Larger, definitive studies are currently in progress to evaluate long-term cosmetic satisfaction. At present, RAP occupies a niche role and can only be justified in patients who have cultural or biological drivers to avoid a neck scar.
Acknowledgments The authors wish to acknowledge the invaluable input of Mrs. Shirley Martin, clinical robotic nurse specialist, and Mr. James Budge, medical student for their assistance in the preparation of the manuscript.
REFERENCES 1. Melton LJ III. The epidemiology of primary hyperparathyroidism in North America. J Bone Miner Res 2002;17 Suppl 2:N12–N17. 2. Pallan S, Rahman MO, Khan AA. Diagnosis and management of primary hyperparathyroidism. BMJ 2012;344:e1013. 3. Venkat R, Kouniavsky G, Tufano RP, Schneider EB, Dackiw AP, Zeiger MA. Long-term outcome in patients with primary hyperparathyroidism who underwent minimally invasive parathyroidectomy. World J Surg 2012; 36:55–60.
E306
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APRIL 2016
4. Delbridge LW, Palazzo FF. First parathyroid surgeon: Sir John Bland–Sutton and the parathyroids. ANZ J Surg 2007;77:1058–1061. 5. Tolley N, Arora A, Palazzo F, et al. Robotic-assisted parathyroidectomy: a feasibility study. Otolaryngol Head Neck Surg 2011;144:859–866. 6. Palazzo FF, Delbridge LW. Minimal-access/minimally invasive parathyroidectomy for primary hyperparathyroidism. Surg Clin North Am 2004;84: 717–734. 7. Agarwal G, Barraclough BH, Robinson BG, Reeve TS, Delbridge LW. Minimally invasive parathyroidectomy using the ‘focused’ lateral approach. I. Results of the first 100 consecutive cases. ANZ J Surg 2002;72: 100–104. 8. Henry JF, Sebag F, Ippolito G. Endoscopic parathyroidectomy through a lateral approach [in French]. J Chir (Paris) 2008;145:470–474. 9. Miccoli P, Berti P, Materazzi G, Donatini G. Minimally invasive video assisted parathyroidectomy (MIVAP). Eur J Surg Oncol 2003;29:188–190. 10. Miccoli P, Bendinelli C, Berti P, Vignali E, Pinchera A, Marcocci C. Video-assisted versus conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study. Surgery 1999;126:1117– 1121; discussion 1121–1122. 11. Ikeda Y, Takami H. Endoscopic parathyroidectomy. Biomed Pharmacother 2000;54 Suppl 1:52s–56s. 12. Kang J, Fan Y, Guo B, Wu B, Zheng Q. Trans-areola single-site endoscopic parathyroidectomy: report of one case. Surg Innov 2013;20: NP16–NP20. 13. Lee KE, Kim HY, Park WS, et al. Postauricular and axillary approach endoscopic neck surgery: a new technique. World J Surg 2009;33:767–772. 14. Chung YS, Choe JH, Kang KH, et al. Endoscopic thyroidectomy for thyroid malignancies: comparison with conventional open thyroidectomy. World J Surg 2007;31:2302–2306; discussion 2307–2308. 15. Ewing DR, Pigazzi A, Wang Y, Ballantyne GH. Robots in the operating room–the history. Semin Laparosc Surg 2004;11:63–71. 16. Moorthy K, Munz Y, Dosis A, et al. Dexterity enhancement with robotic surgery. Surg Endosc 2004;18:790–795. 17. Karagkounis G, Uzun DD, Mason DP, Murthy SC, Berber E. Robotic surgery for primary hyperparathyroidism. Surg Endosc 2014;28:2702–2707. 18. Noureldine SI, Lewing N, Tufano RP, Kandil E. The role of the roboticassisted transaxillary gasless approach for the removal of parathyroid adenomas. ORL J Otorhinolaryngol Relat Spec 2014;76:19–24. 19. Agarwal G, Barraclough BH, Reeve TS, Delbridge LW. Minimally invasive parathyroidectomy using the ‘focused’ lateral approach. II. Surgical technique. ANZ J Surg 2002;72:147–151. 20. Kaul S, Shah NL, Menon M. Learning curve using robotic surgery. Curr Urol Rep 2006;7:125–129. 21. The British Association of Endocrine & Thyroid Surgeons, Fourth National Audit Report; 2012. Available at: http://www.baets.org.uk/wp-content/ uploads/2013/05/4th-National-Audit.pdf. Accessed June 1, 2014. 22. Miccoli P, Berti P, Materazzi G, Massi M, Picone A, Minuto MN. Results of video-assisted parathyroidectomy: single institution’s six-year experience. World J Surg 2004;28:1216–1218. 23. Lee J, Kwon IS, Bae EH, Chung WY. Comparative analysis of oncological outcomes and quality of life after robotic versus conventional open thyroidectomy with modified radical neck dissection in patients with papillary thyroid carcinoma and lateral neck node metastases. J Clin Endocrinol Metab 2013;98:2701–2708. 24. Weber T, Keller M, Hense I, et al. Effect of parathyroidectomy on quality of life and neuropsychological symptoms in primary hyperparathyroidism. World J Surg 2007;31:1202–1209. 25. Allah KC, Yeo S, Kossoko H, Assi Dje` Bi Dje` V, Richard Kadio M. Keloid scars on black skin: myth or reality [in French]. Ann Chir Plast Esthet 2013;58:115–122. 26. Foley CS, Agcaoglu O, Siperstein AE, Berber E. Robotic transaxillary endocrine surgery: a comparison with conventional open technique. Surg Endosc 2012;26:2259–2266. 27. Linos D, Economopoulos KP, Kiriakopoulos A, Linos E, Petralias A. Scar perceptions after thyroid and parathyroid surgery: comparison of minimal and conventional approaches. Surgery 2013;153:400–407. 28. Landry CS, Grubbs EG, Morris GS, et al. Robot assisted transaxillary surgery (RATS) for the removal of thyroid and parathyroid glands. Surgery 2011;149:549–555. 29. Garas G, Ibrahim A, Ashrafian H, et al. Evidence-based surgery: barriers, solutions, and the role of evidence synthesis. World J Surg 2012;36: 1723–1731. 30. Duncan JA, Bond JS, Mason T, et al. Visual analogue scale scoring and ranking: a suitable and sensitive method for assessing scar quality? Plast Reconstr Surg 2006;118:909–918. 31. Crossley KM, Bennell KL, Cowan SM, Green S. Analysis of outcome measures for persons with patellofemoral pain: which are reliable and valid? Arch Phys Med Rehabil 2004;85:815–822. 32. Fraker DL, Harsono H, Lewis R. Minimally invasive parathyroidectomy: benefits and requirements of localization, diagnosis, and intraoperative PTH monitoring. Long-term results. World J Surg 2009;33:2256–2265. 33. Trehan A, Dunn TJ. The robotic surgery monopoly is a poor deal. BMJ 2013;347:f7470.
