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Technological Innovations in Surgical Approach for Thyroid Cancer

Technological Innovations in Surgical Approach for Thyroid Cancer Hindawi Publishing Corporation Journal of Oncology Volume 2010, Article ID 490719, 6 pages doi:10.1155/2010/490719 Review Article Technological Innovations in Surgical Approach for Thyroid Cancer Brian Hung-Hin Lang and Chung-Yau Lo Division of Endocrine Surgery, Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong Correspondence should be addressed to Brian Hung-Hin Lang, blang@hkucc.hku.hk Received 17 August 2009; Revised 15 April 2010; Accepted 27 June 2010 Academic Editor: Steven K. Libutti Copyright © 2010 B. H.-H. Lang and C.-Y. Lo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Over the last decade, surgeons have witnessed dramatic changes in surgical practice as a result of the introduction of new technological advancement. Some of these changes include refinement of techniques in thyroid cancer surgery. The development of various endoscopic thyroidectomy techniques, the addition of the da Vinci robot, and the use of operative adjuncts in thyroid surgery, such as intraoperative neuromonitoring and quick intraoperative parathyroid hormone, have made thyroid cancer surgery not only safer and better accepted by patients with thyroid cancer but also offer them more surgical treatment options. 1. Introduction such as intraoperative neuromonitoring (IONM) and quick intraoperative parathyroid hormone (IOPTH). New technologies have had a positive impact on our ability to diagnose and treat many surgical conditions [1]. Over the last decade, surgeons have witnessed dramatic changes 2. Endoscopic Thyroidectomy in surgical practice as a result of the introduction of new technologies or technological advancement. Thyroid cancer The application of endoscopic visualization to thyroid is the commonest endocrine-related tumor. In our locality, surgery has allowed surgeons to perform thyroidectomy its age-adjusted incidence has doubled over the last 25 through incisions far smaller and less visible than the years, and a similar trend has been reported elsewhere conventional Kocher’s incision—the so-called “less is more.” [2]. New technologies have had important influence in In general, these endoscopic techniques attempt to minimiz- the management of this disease. In addition to improving ing the extent of dissection, improving cosmesis, reducing the preoperative diagnostic accuracy and cancer staging postoperative pain, shortening hospital stay, and enhancing with various imaging modalities, the techniques of thyroid postoperative recovery. Michel Gagner was the first to apply cancer surgery have been refined and evolved in this endoscopic technique to neck surgery when he reported a era of technological advancement. In applying these new totally endoscopic subtotal parathyroidectomy for a 37-year- technologies, it is believed that surgical morbidity can be old man suffering from familial hyperparathyroidism [4]. further reduced, hospital stay shortened, and patient satis- Although the endoscopic procedure took over 5 hours, it faction enhanced [3]. The present paper aimed at evaluating demonstrated the technical feasibility and safety. Over the how some of these new technological innovations might turn of the last century, an increasing number of different improve patient outcomes and offer new surgical treatment endoscopic techniques have been described and may be options for patients diagnosed with thyroid cancer. These categorized into namely cervical or direct and extracervical innovations include the development of various endoscopic or indirect approaches [5]. The former is considered as thyroidectomy techniques, the addition of the da Vinci robot truly minimally invasive since the skin incisions are small surgical system, as well as the use of operative adjuncts in the neck with direct access to the thyroid gland. On 2 Journal of Oncology the other hand, the extracervical approach is considered was technically demanding and time consuming because of as an endoscopic instead of minimally invasive approach unintentional easy gas leakage and frequent interference of because incisions are made distant from the neck and so the 3 operating surgical instruments in the small available the procedure requires more extensive tissue dissections [6]. space in the axilla [15]. Kang et al. modified this technique However, despite its invasiveness, it offers superior early by making this approach gasless with the space maintained cosmetic outcome because potentially unsightly scars can be by a specially designed skin-lifting external retractor [16]. hidden. This approach has been adopted more often in Asian In this approach, the procedure began with a 4 cm to 5 cm countries where cosmesis seems to be of greater concern. incision in the axilla and then a subcutaneous space was created from the axilla to the thyroid gland. To avoid the problem of interference of instruments, an additional 5 mm 2.1. Cervical/Direct Approaches. These approaches include port was inserted in the chest area for medial retraction of the the endoscopic lateral cervical approach and the mini- thyroid gland. Kang et al. recently reported their experience mally invasive video-assisted thyroidectomy (MIVAT). In with this approach after performing 581 cases [16]. Among the endoscopic lateral cervical approach, two 2.5 mm and these patients, 410 patients had low-risk PTC. In their series, one 10 mm trocars are inserted under direct vision along concomitant central neck dissection was performed and the the anterior border of the sternocleidomastoid muscle on rate of lymph node metastasis was 27.3% [16]. the side of resection. Using endoscopic instruments, the To further increase the degree of angulations and free- dissection starts from the lateral aspect of the thyroid gland dom of interference between instruments, a combined axillo- and moves medially with identification of the recurrent breast approach was developed utilizing 2 circumareolar laryngeal nerve (RLN), parathyroid glands and skeleton- trocars in the breast and a single trocar in the ipsilateral isation of the superior and inferior thyroid vessels [7]. axilla. This approach was later modified by using bilateral Excellent visualization of RLN and parathyroid glands is axillary ports to allow better exposure to both sides of possible with magnification by the endoscope. However, the thyroid compartment. This approach is now known this technique is limited to unilateral thyroid resection and as the bilateral axillo-breast approach (BABA). Despite its application in thyroid cancer surgery is restricted to the extensive tissue dissection, when compared with the subcentimeter papillary thyroid carcinoma (PTC) detected conventional open approach, BABA has been shown to have by high-resolution ultrasound machines. In contrast, the similar results in terms of transient hypocalcemia, bleeding, MIVAT would be preferred if bilateral thyroid resection is permanent RLN paralysis and length of hospital stay [17]. required because the incision is made in the middle instead More recently, a Korean group tried to eliminate wounds of the lateral aspect of the neck. A 1.5 cm incision is made around the chest or breast areas all together by making in the middle of the neck about 2 cm above the sternal incisions in the axilla and postauricular areas instead. They notch. Blunt dissection is then carried out to separate the reported a small series of 10 patients using this approach strap muscle from underlying thyroid lobe. A 5 mm 30 and 7 underwent bilateral thyroid resection for low-risk PTC. degree endoscope is placed inside the 1.5 cm wound for They demonstrated the feasibility of this technique of scarless lighting and visualization. The procedure is performed under (in the neck) thyroid surgery [18]. endoscopic view with the operating space maintained by external retraction. This technique was first applied for selected benign thyroid conditions by Miccoli et al. in 2000 3. Robotic-Assisted Thyroidectomy [8]. However, with improvement in techniques, MIVAT has become increasingly adopted for low-to-intermediate risk The application and feasibility of the endoscopic approach differentiated thyroid cancer [9]. MIVAT has been shown was given a further boost with the availability of various to achieve similar completeness of resection [10, 11]and 5- robotic systems such as the da Vinci system (Intuitive year survival outcomes as those with low and intermediate Surgical, Sunnyvale, California). Unlike other cancers such risk PTC undergoing conventional thyroidectomy [9]. In as prostate cancer, the initial enthusiasm of using the robot addition, it has been shown that a concomitant central in thyroid cancers was not great because of its relatively neck dissection is technically feasible in MIVAT during high cost, bulkiness of the robotic arm, and long operating initial total thyroidectomy [12]. Also, for patients with low time. However, since the publication of two large surgical risk PTC with concomitant lateral lymph node metastases, series demonstrating the feasibility and safety of robotic- a minimally invasive video-assisted functional lateral neck assisted thyroidectomy in differentiated thyroid carcinoma, dissection through a small neck incision is also technically an increasing number of specialized surgical centers world- possible [13]. wide are beginning to accept and perform this procedure. The theoretical advantages of using the robot over the endo- 2.2. Extracervical/Indirect Endoscopic Approaches. Unlike the scopic approach include the three-dimensional view offer to cervical approaches, these approaches involve making inci- the operating surgeon, the flexible robotic instruments with sions either in the chest, breast, and/or axilla to hide the seven degree of freedom and 90 articulation, the increased scars with clothing [14]. Ikede et al. first described these tactile sensation, and the ability to filter any hand tremors approaches by placing three ports in the axilla with low- [19]. Kang et al. recently reported their experience of 200 pressure gas insufflation for maintaining the operating space. robot-assisted total thyroidectomy using the gasless transax- Although cosmetic results were excellent, the procedure illary approach for low-risk PTC with concomitant central Journal of Oncology 3 neck dissection and found excellent short-term results in electrodes or poor contact of the probe with the nerve due to terms of postoperative pain and patients’ satisfaction [20]. inadequate exposure [28]. Perhaps, direct vagal stimulation This was followed briefly by another report of 338 benign could possibly reduce some of these errors but need more and malignant cases using the same transaxillary [21]. To unnecessary dissection. Even more intriguing is the fact that date, this group has performed over 1000 cases. A separate this technique is also associated with false negative results, Korean group also reported similar results using the da albeit rarely. In our experience, among 271 nerves at risk, Vinci robot via the BABA technique [22]. Although both 15 (5.5%) ended with RLN palsy but of these, 7 still had techniques have been demonstrated to be feasible and safe, a positive IONM signals. Therefore, it seems that IONM they have been limited to a few high-volume specialized might not be able to detect “sublethal” injury to RLN. It is centers. The surgeons performing these operations have had possible that the action potential could be propagated along years of operating experience with the endoscopic approach the neural pathway, as detected by the IONM, but not to the and so the learning curve for a novel, nonendoscopic extent of initiating laryngeal muscle contraction during the thyroid surgeon or someone who predominantly perform postoperative period [25, 28]. Fortunately, all these injuries open thyroid procedures, remains undefined but is likely would invariably recover. to be longer than one might think. Furthermore, better On the other hand, although the objective of the use comparative studies such as a randomized controlled trial of this device is to avoid RLN injury during thyroid between robotic-assisted and endoscopic thyroidectomy are surgery, the evidence of supporting its routine use has been needed in order to better assess the added patient outcome weak. The first multicenter study including 29,998 RLNs benefits over the latter approach. at risk confirmed that the incidence of RLN palsy was not significantly reduced by the additional use of IONM when routine RLN identification was performed [27]. There were more than 20 publications addressing this issue but 4. Surgical Adjunct: IONM majority of these studies were heterogeneous in terms of RLN injury is a leading cause of litigation in thyroid surgery patients’ characteristics (such as primary operations versus reoperations or benign versus malignant goiters), IONM [23]. To those with this injury, it not only affects the voice quality but also diminishes the overall quality of life because techniques and the extent of resection (i.e., total versus of communication, social and work-related problems [24]. subtotal lobectomy). A recent literature review could not definitely draw confirm conclusions or evidence on the Routine RLN identification is currently the gold standard of care in thyroid surgery. However, with the availability of effectiveness of IONM in reducing RLN injury in thyroid IONM, the issues are whether this new technology could surgery [26]. Furthermore, most studies were either case- further enhance RLN preservation and reduce the risk of series with no control group or retrospective studies with iatrogenic RLN injury in thyroid surgery or thyroid cancer inadequate statistical power to demonstrate a difference surgery in particular. between those with or without using IONM. In fact, a Although IONM has been around for over 3 decades, randomized study utilizing approximately 7,000 patients in its widespread usage in the surgical practice only dates each arm of patients undergoing thyroidectomy with or without IONM will be required to have adequate statistical back to 5–10 years. There has been an increased interest in applying this technique for thyroid surgery because of powertoshowadifference in outcome with reference to RLN the introduction of new and user-friendly devices from paralysis [26, 27]. Interestingly though, the first prospective randomized study comparing IONM with routine RLN technological advance [25]. Currently, there are two types of IONM systems, namely, those with electromyographic visualization only was recently published [28]. In this study, (EMG) documentation and those without EMG documenta- approximately 500 patients were randomized into each tion. The former involves RLN stimulation with registration arm. The number of patients recruited in each arm was of the elicited laryngeal muscle activity through endoscopic based on the principle of detecting a 2% difference in the incidence of transient RLN injury with a 90% probability at insertion of electrodes into the vocal fold or with the use of endotracheal surface electrodes. The latter utilizes RLN P < .05. This study did demonstrate a statistically significant stimulation with observation of posterior cricoarythenoid difference in reducing transient RLN injury when IONM was adopted in comparison with RLN visualization only. muscle contraction or palpation or intraoperative inspection of vocal cord function [26, 27]. To date, there is no consensus However, as expected, the rate of permanent RLN injury on which is the best system, and the choice depends on was similar in the two study arms because of inadequate the availability of which system in your institution and statistical power. Nevertheless, despite the inadequate power the operator familiarity or experience. Regardless of which of most published IONM studies, there seemed to be a systems, there are potential flaws and pitfalls. In general, the trend toward improved RLN protection with the use of positive predictive value (PPV) is proportionally low with this new technology [26]. In addition, the IONM may be this technology. That means that when a nerve has no signal of potential benefit for “difficult” cases such as reoperative thyroidectomy, locally advanced thyroid cancers or central during stimulation, it does not mean that it is injured. In fact, in our experience, the PPV was only 15% in low-risk neck dissection for cancer recurrence. Perhaps, for the thyroid surgery, that is, approximately only 1 out of 9 RLNs novel and relatively inexperienced surgeons, the IONM might prove to be extremely invaluable for these difficult with no signals had an actual injury. This might be due to some technical errors such as detachment or displacement of cases. 4 Journal of Oncology 5. Surgical Adjunct: IOPTH or Quick in 100 consecutive patients (including 33 patients with differentiated thyroid cancer) who underwent either total Intraoperative Parathyroid Assay (qPTH) or completion thyroidectomy, we found that a normal level as an Assessment of Posthyroidectomy of IOPTH at 10 mins or a level less than 75% decline in Hypoparathyroidism IOPTH at 10 mins after excision of thyroid gland accu- rately identified normocalcemia [38]. It was suggested that Hypoparathyroidism is a common complication after bilat- eral thyroid resections or total thyroidectomy. Up to 30% intraoperative or early postoperative parathyroid hormone assay might be a sensitive tool to confirm postoperative of patients after total thyroidectomy develop temporary normocalcaemia and identify patients atrisk of developing hypoparathyroidism [29]. There are many identifiable risk postoperative hypocalcaemia. Since then, up to 30 different factors leading to postoperative hypoparathyroidism includ- investigators have published their results of using various ing thyroidectomy for thyrotoxicosis and thyroid cancer, thyroid reoperations, reduced stores of vitamin D, increased different IOPTH assays in predicting hypocalcemia after total thyroidectomy. The IOPTH levels and their rate of extent of thyroid resection, and need of concomitant decline at various time points after surgery could be utilized central neck dissection [30, 31]. Patients undergoing thy- roidectomy for thyroid cancer are particularly prone to for prediction of postoperative hypocalcaemia with variable sensitivity, specificity, and accuracy [39, 40]. However, based hypoparathyroidism because they often need a more com- on two evidence-based reviews, it was recommended that plete thyroid resection together with neck dissection. In fact, total thyroidectomy and routine concomitant central neck the IOPTH level within a few hours after thyroid surgery could accurately predict postoperative normocalcaemia and dissection has now been increasingly practiced worldwide identify patients at-risk of developing hypocalcemia, par- for almost types of well-differentiated thyroid cancer to ticularly severe, symptomatic hypocalcemia [34, 41]. It achieve lower recurrences, better disease-free survival, and was suggested that patients could be stratified into high- enhanced postoperative athyroglobulinemia [32]. However, it has been shown that up to 60% of patients after or low-risk groups and PTH should be measured at 1– 6 hrs after operation in comparison to preoperative PTH. concomitant central neck dissection could develop transient A < or > 65% decline at 6 hours after operation should hypocalcemia secondary to the frequent occurrence of unin- tentional or incidental parathyroidectomy [33]. Therefore, allow early discharge or facilitate the decision of early calcium supplement. On the other hand, a strategy of 2 in the presence of such a high incidence of postoperative cut-off points should be considered with a high accuracy. hypoparathyroidism, the need of routine postoperative inpa- tient calcium monitoring remains questionable after thyroid A <50% decline within few hours after surgery allowed early discharge while a >90% decline necessitated early cancer surgery while the early routine administration of oral calcium and/or vitamin D supplements seems to be relevant calcium supplement because of the accuracy in predicting normocalcaemia and hypocalcaemia, respectively [41]. For and can facilitate the early discharge from hospital shortly those patients with 50%–90% decline, either serial calcium after surgery without developing unpleasant hypocalcemic symptoms [34]. In fact, a recent randomized study supported monitoring or routine treatment should be considered. In the AES guideline, one single serum PTH measurement is this strategy because routine administration of oral calcium recommended at 4 hrs after operation [42]. A normal PTH was shown to markedly reduce the severity and symptoms of hypocalcemia [35]. However, the adoption of this strat- can predict normocalcaemia, and patients can be discharged early with 7% subsequently developing mild hypocalcaemia. egy could lead to overtreatment in patients who do not For patients with undetectable PTH level, oral calcium and have hypocalcaemia leading to rebound hypercalcemia and vitamin D analogue should be administered early to avoid increased medication costs. On the other hand, this strategy symptomatic hypocalcaemia. Intermediate or subnormal might lead to inadequate treatment in patients with severe symptomatic hypocalcaemia as oral calcium alone may not PTH level is a less accurate predictor of hypocalcaemia. In that case, oral calcium should commence or patients should fully correct the hypocalcemia and so vitamin D supplements be monitored with serial calcium levels for the need of is indicated in such situation [36]. On the other hand, inpatient serial close monitoring of calcium and/or vitamin D analogue [42]. Therefore, PTH serum calcium is recommended after total thyroidectomy assay can now be considered as a perioperative adjunct to because most symptomatic hypocalcemia occurs around 24– predict normocalcaemia or hypocalcaemia with reasonable 28 hours after surgery [37]. A 24-hour or longer hospital accuracy. It can facilitate early discharge, avoid routine stay is invariably required. Therefore, efforts aremadeto calcium replacement, facilitate early calcium replacement to shorten hospital stays, decrease biochemical blood tests, avoid symptomatic hypocalcaemia and decrease overall cost and reduce hospital costs by adopting other strategies to as well as increase patients’ satisfaction. achieve early prediction of postthyroidectomy hypocalcemia. With the availability of IOPTH and wide application in patients undergoing minimally invasive parathyroidectomy 6. Conclusions to predict postoperative cure, this new surgical adjunct has been applied to thyroid surgery to monitor parathyroid New technologies have undoubtedly had a positive impact on function and to predict the occurrence of postoperative the surgical management of thyroid cancer. The application normocalcaemia or hypocalcaemia. 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Technological Innovations in Surgical Approach for Thyroid Cancer

Journal of Oncology , Volume 2010 – Jul 27, 2010

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Copyright © 2010 Brian Hung-Hin Lang and Chung-Yau Lo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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1687-8450
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1687-8469
DOI
10.1155/2010/490719
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Abstract

Hindawi Publishing Corporation Journal of Oncology Volume 2010, Article ID 490719, 6 pages doi:10.1155/2010/490719 Review Article Technological Innovations in Surgical Approach for Thyroid Cancer Brian Hung-Hin Lang and Chung-Yau Lo Division of Endocrine Surgery, Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong Correspondence should be addressed to Brian Hung-Hin Lang, blang@hkucc.hku.hk Received 17 August 2009; Revised 15 April 2010; Accepted 27 June 2010 Academic Editor: Steven K. Libutti Copyright © 2010 B. H.-H. Lang and C.-Y. Lo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Over the last decade, surgeons have witnessed dramatic changes in surgical practice as a result of the introduction of new technological advancement. Some of these changes include refinement of techniques in thyroid cancer surgery. The development of various endoscopic thyroidectomy techniques, the addition of the da Vinci robot, and the use of operative adjuncts in thyroid surgery, such as intraoperative neuromonitoring and quick intraoperative parathyroid hormone, have made thyroid cancer surgery not only safer and better accepted by patients with thyroid cancer but also offer them more surgical treatment options. 1. Introduction such as intraoperative neuromonitoring (IONM) and quick intraoperative parathyroid hormone (IOPTH). New technologies have had a positive impact on our ability to diagnose and treat many surgical conditions [1]. Over the last decade, surgeons have witnessed dramatic changes 2. Endoscopic Thyroidectomy in surgical practice as a result of the introduction of new technologies or technological advancement. Thyroid cancer The application of endoscopic visualization to thyroid is the commonest endocrine-related tumor. In our locality, surgery has allowed surgeons to perform thyroidectomy its age-adjusted incidence has doubled over the last 25 through incisions far smaller and less visible than the years, and a similar trend has been reported elsewhere conventional Kocher’s incision—the so-called “less is more.” [2]. New technologies have had important influence in In general, these endoscopic techniques attempt to minimiz- the management of this disease. In addition to improving ing the extent of dissection, improving cosmesis, reducing the preoperative diagnostic accuracy and cancer staging postoperative pain, shortening hospital stay, and enhancing with various imaging modalities, the techniques of thyroid postoperative recovery. Michel Gagner was the first to apply cancer surgery have been refined and evolved in this endoscopic technique to neck surgery when he reported a era of technological advancement. In applying these new totally endoscopic subtotal parathyroidectomy for a 37-year- technologies, it is believed that surgical morbidity can be old man suffering from familial hyperparathyroidism [4]. further reduced, hospital stay shortened, and patient satis- Although the endoscopic procedure took over 5 hours, it faction enhanced [3]. The present paper aimed at evaluating demonstrated the technical feasibility and safety. Over the how some of these new technological innovations might turn of the last century, an increasing number of different improve patient outcomes and offer new surgical treatment endoscopic techniques have been described and may be options for patients diagnosed with thyroid cancer. These categorized into namely cervical or direct and extracervical innovations include the development of various endoscopic or indirect approaches [5]. The former is considered as thyroidectomy techniques, the addition of the da Vinci robot truly minimally invasive since the skin incisions are small surgical system, as well as the use of operative adjuncts in the neck with direct access to the thyroid gland. On 2 Journal of Oncology the other hand, the extracervical approach is considered was technically demanding and time consuming because of as an endoscopic instead of minimally invasive approach unintentional easy gas leakage and frequent interference of because incisions are made distant from the neck and so the 3 operating surgical instruments in the small available the procedure requires more extensive tissue dissections [6]. space in the axilla [15]. Kang et al. modified this technique However, despite its invasiveness, it offers superior early by making this approach gasless with the space maintained cosmetic outcome because potentially unsightly scars can be by a specially designed skin-lifting external retractor [16]. hidden. This approach has been adopted more often in Asian In this approach, the procedure began with a 4 cm to 5 cm countries where cosmesis seems to be of greater concern. incision in the axilla and then a subcutaneous space was created from the axilla to the thyroid gland. To avoid the problem of interference of instruments, an additional 5 mm 2.1. Cervical/Direct Approaches. These approaches include port was inserted in the chest area for medial retraction of the the endoscopic lateral cervical approach and the mini- thyroid gland. Kang et al. recently reported their experience mally invasive video-assisted thyroidectomy (MIVAT). In with this approach after performing 581 cases [16]. Among the endoscopic lateral cervical approach, two 2.5 mm and these patients, 410 patients had low-risk PTC. In their series, one 10 mm trocars are inserted under direct vision along concomitant central neck dissection was performed and the the anterior border of the sternocleidomastoid muscle on rate of lymph node metastasis was 27.3% [16]. the side of resection. Using endoscopic instruments, the To further increase the degree of angulations and free- dissection starts from the lateral aspect of the thyroid gland dom of interference between instruments, a combined axillo- and moves medially with identification of the recurrent breast approach was developed utilizing 2 circumareolar laryngeal nerve (RLN), parathyroid glands and skeleton- trocars in the breast and a single trocar in the ipsilateral isation of the superior and inferior thyroid vessels [7]. axilla. This approach was later modified by using bilateral Excellent visualization of RLN and parathyroid glands is axillary ports to allow better exposure to both sides of possible with magnification by the endoscope. However, the thyroid compartment. This approach is now known this technique is limited to unilateral thyroid resection and as the bilateral axillo-breast approach (BABA). Despite its application in thyroid cancer surgery is restricted to the extensive tissue dissection, when compared with the subcentimeter papillary thyroid carcinoma (PTC) detected conventional open approach, BABA has been shown to have by high-resolution ultrasound machines. In contrast, the similar results in terms of transient hypocalcemia, bleeding, MIVAT would be preferred if bilateral thyroid resection is permanent RLN paralysis and length of hospital stay [17]. required because the incision is made in the middle instead More recently, a Korean group tried to eliminate wounds of the lateral aspect of the neck. A 1.5 cm incision is made around the chest or breast areas all together by making in the middle of the neck about 2 cm above the sternal incisions in the axilla and postauricular areas instead. They notch. Blunt dissection is then carried out to separate the reported a small series of 10 patients using this approach strap muscle from underlying thyroid lobe. A 5 mm 30 and 7 underwent bilateral thyroid resection for low-risk PTC. degree endoscope is placed inside the 1.5 cm wound for They demonstrated the feasibility of this technique of scarless lighting and visualization. The procedure is performed under (in the neck) thyroid surgery [18]. endoscopic view with the operating space maintained by external retraction. This technique was first applied for selected benign thyroid conditions by Miccoli et al. in 2000 3. Robotic-Assisted Thyroidectomy [8]. However, with improvement in techniques, MIVAT has become increasingly adopted for low-to-intermediate risk The application and feasibility of the endoscopic approach differentiated thyroid cancer [9]. MIVAT has been shown was given a further boost with the availability of various to achieve similar completeness of resection [10, 11]and 5- robotic systems such as the da Vinci system (Intuitive year survival outcomes as those with low and intermediate Surgical, Sunnyvale, California). Unlike other cancers such risk PTC undergoing conventional thyroidectomy [9]. In as prostate cancer, the initial enthusiasm of using the robot addition, it has been shown that a concomitant central in thyroid cancers was not great because of its relatively neck dissection is technically feasible in MIVAT during high cost, bulkiness of the robotic arm, and long operating initial total thyroidectomy [12]. Also, for patients with low time. However, since the publication of two large surgical risk PTC with concomitant lateral lymph node metastases, series demonstrating the feasibility and safety of robotic- a minimally invasive video-assisted functional lateral neck assisted thyroidectomy in differentiated thyroid carcinoma, dissection through a small neck incision is also technically an increasing number of specialized surgical centers world- possible [13]. wide are beginning to accept and perform this procedure. The theoretical advantages of using the robot over the endo- 2.2. Extracervical/Indirect Endoscopic Approaches. Unlike the scopic approach include the three-dimensional view offer to cervical approaches, these approaches involve making inci- the operating surgeon, the flexible robotic instruments with sions either in the chest, breast, and/or axilla to hide the seven degree of freedom and 90 articulation, the increased scars with clothing [14]. Ikede et al. first described these tactile sensation, and the ability to filter any hand tremors approaches by placing three ports in the axilla with low- [19]. Kang et al. recently reported their experience of 200 pressure gas insufflation for maintaining the operating space. robot-assisted total thyroidectomy using the gasless transax- Although cosmetic results were excellent, the procedure illary approach for low-risk PTC with concomitant central Journal of Oncology 3 neck dissection and found excellent short-term results in electrodes or poor contact of the probe with the nerve due to terms of postoperative pain and patients’ satisfaction [20]. inadequate exposure [28]. Perhaps, direct vagal stimulation This was followed briefly by another report of 338 benign could possibly reduce some of these errors but need more and malignant cases using the same transaxillary [21]. To unnecessary dissection. Even more intriguing is the fact that date, this group has performed over 1000 cases. A separate this technique is also associated with false negative results, Korean group also reported similar results using the da albeit rarely. In our experience, among 271 nerves at risk, Vinci robot via the BABA technique [22]. Although both 15 (5.5%) ended with RLN palsy but of these, 7 still had techniques have been demonstrated to be feasible and safe, a positive IONM signals. Therefore, it seems that IONM they have been limited to a few high-volume specialized might not be able to detect “sublethal” injury to RLN. It is centers. The surgeons performing these operations have had possible that the action potential could be propagated along years of operating experience with the endoscopic approach the neural pathway, as detected by the IONM, but not to the and so the learning curve for a novel, nonendoscopic extent of initiating laryngeal muscle contraction during the thyroid surgeon or someone who predominantly perform postoperative period [25, 28]. Fortunately, all these injuries open thyroid procedures, remains undefined but is likely would invariably recover. to be longer than one might think. Furthermore, better On the other hand, although the objective of the use comparative studies such as a randomized controlled trial of this device is to avoid RLN injury during thyroid between robotic-assisted and endoscopic thyroidectomy are surgery, the evidence of supporting its routine use has been needed in order to better assess the added patient outcome weak. The first multicenter study including 29,998 RLNs benefits over the latter approach. at risk confirmed that the incidence of RLN palsy was not significantly reduced by the additional use of IONM when routine RLN identification was performed [27]. There were more than 20 publications addressing this issue but 4. Surgical Adjunct: IONM majority of these studies were heterogeneous in terms of RLN injury is a leading cause of litigation in thyroid surgery patients’ characteristics (such as primary operations versus reoperations or benign versus malignant goiters), IONM [23]. To those with this injury, it not only affects the voice quality but also diminishes the overall quality of life because techniques and the extent of resection (i.e., total versus of communication, social and work-related problems [24]. subtotal lobectomy). A recent literature review could not definitely draw confirm conclusions or evidence on the Routine RLN identification is currently the gold standard of care in thyroid surgery. However, with the availability of effectiveness of IONM in reducing RLN injury in thyroid IONM, the issues are whether this new technology could surgery [26]. Furthermore, most studies were either case- further enhance RLN preservation and reduce the risk of series with no control group or retrospective studies with iatrogenic RLN injury in thyroid surgery or thyroid cancer inadequate statistical power to demonstrate a difference surgery in particular. between those with or without using IONM. In fact, a Although IONM has been around for over 3 decades, randomized study utilizing approximately 7,000 patients in its widespread usage in the surgical practice only dates each arm of patients undergoing thyroidectomy with or without IONM will be required to have adequate statistical back to 5–10 years. There has been an increased interest in applying this technique for thyroid surgery because of powertoshowadifference in outcome with reference to RLN the introduction of new and user-friendly devices from paralysis [26, 27]. Interestingly though, the first prospective randomized study comparing IONM with routine RLN technological advance [25]. Currently, there are two types of IONM systems, namely, those with electromyographic visualization only was recently published [28]. In this study, (EMG) documentation and those without EMG documenta- approximately 500 patients were randomized into each tion. The former involves RLN stimulation with registration arm. The number of patients recruited in each arm was of the elicited laryngeal muscle activity through endoscopic based on the principle of detecting a 2% difference in the incidence of transient RLN injury with a 90% probability at insertion of electrodes into the vocal fold or with the use of endotracheal surface electrodes. The latter utilizes RLN P < .05. This study did demonstrate a statistically significant stimulation with observation of posterior cricoarythenoid difference in reducing transient RLN injury when IONM was adopted in comparison with RLN visualization only. muscle contraction or palpation or intraoperative inspection of vocal cord function [26, 27]. To date, there is no consensus However, as expected, the rate of permanent RLN injury on which is the best system, and the choice depends on was similar in the two study arms because of inadequate the availability of which system in your institution and statistical power. Nevertheless, despite the inadequate power the operator familiarity or experience. Regardless of which of most published IONM studies, there seemed to be a systems, there are potential flaws and pitfalls. In general, the trend toward improved RLN protection with the use of positive predictive value (PPV) is proportionally low with this new technology [26]. In addition, the IONM may be this technology. That means that when a nerve has no signal of potential benefit for “difficult” cases such as reoperative thyroidectomy, locally advanced thyroid cancers or central during stimulation, it does not mean that it is injured. In fact, in our experience, the PPV was only 15% in low-risk neck dissection for cancer recurrence. Perhaps, for the thyroid surgery, that is, approximately only 1 out of 9 RLNs novel and relatively inexperienced surgeons, the IONM might prove to be extremely invaluable for these difficult with no signals had an actual injury. This might be due to some technical errors such as detachment or displacement of cases. 4 Journal of Oncology 5. Surgical Adjunct: IOPTH or Quick in 100 consecutive patients (including 33 patients with differentiated thyroid cancer) who underwent either total Intraoperative Parathyroid Assay (qPTH) or completion thyroidectomy, we found that a normal level as an Assessment of Posthyroidectomy of IOPTH at 10 mins or a level less than 75% decline in Hypoparathyroidism IOPTH at 10 mins after excision of thyroid gland accu- rately identified normocalcemia [38]. It was suggested that Hypoparathyroidism is a common complication after bilat- eral thyroid resections or total thyroidectomy. Up to 30% intraoperative or early postoperative parathyroid hormone assay might be a sensitive tool to confirm postoperative of patients after total thyroidectomy develop temporary normocalcaemia and identify patients atrisk of developing hypoparathyroidism [29]. There are many identifiable risk postoperative hypocalcaemia. Since then, up to 30 different factors leading to postoperative hypoparathyroidism includ- investigators have published their results of using various ing thyroidectomy for thyrotoxicosis and thyroid cancer, thyroid reoperations, reduced stores of vitamin D, increased different IOPTH assays in predicting hypocalcemia after total thyroidectomy. The IOPTH levels and their rate of extent of thyroid resection, and need of concomitant decline at various time points after surgery could be utilized central neck dissection [30, 31]. Patients undergoing thy- roidectomy for thyroid cancer are particularly prone to for prediction of postoperative hypocalcaemia with variable sensitivity, specificity, and accuracy [39, 40]. However, based hypoparathyroidism because they often need a more com- on two evidence-based reviews, it was recommended that plete thyroid resection together with neck dissection. In fact, total thyroidectomy and routine concomitant central neck the IOPTH level within a few hours after thyroid surgery could accurately predict postoperative normocalcaemia and dissection has now been increasingly practiced worldwide identify patients at-risk of developing hypocalcemia, par- for almost types of well-differentiated thyroid cancer to ticularly severe, symptomatic hypocalcemia [34, 41]. It achieve lower recurrences, better disease-free survival, and was suggested that patients could be stratified into high- enhanced postoperative athyroglobulinemia [32]. However, it has been shown that up to 60% of patients after or low-risk groups and PTH should be measured at 1– 6 hrs after operation in comparison to preoperative PTH. concomitant central neck dissection could develop transient A < or > 65% decline at 6 hours after operation should hypocalcemia secondary to the frequent occurrence of unin- tentional or incidental parathyroidectomy [33]. Therefore, allow early discharge or facilitate the decision of early calcium supplement. On the other hand, a strategy of 2 in the presence of such a high incidence of postoperative cut-off points should be considered with a high accuracy. hypoparathyroidism, the need of routine postoperative inpa- tient calcium monitoring remains questionable after thyroid A <50% decline within few hours after surgery allowed early discharge while a >90% decline necessitated early cancer surgery while the early routine administration of oral calcium and/or vitamin D supplements seems to be relevant calcium supplement because of the accuracy in predicting normocalcaemia and hypocalcaemia, respectively [41]. For and can facilitate the early discharge from hospital shortly those patients with 50%–90% decline, either serial calcium after surgery without developing unpleasant hypocalcemic symptoms [34]. In fact, a recent randomized study supported monitoring or routine treatment should be considered. In the AES guideline, one single serum PTH measurement is this strategy because routine administration of oral calcium recommended at 4 hrs after operation [42]. A normal PTH was shown to markedly reduce the severity and symptoms of hypocalcemia [35]. However, the adoption of this strat- can predict normocalcaemia, and patients can be discharged early with 7% subsequently developing mild hypocalcaemia. egy could lead to overtreatment in patients who do not For patients with undetectable PTH level, oral calcium and have hypocalcaemia leading to rebound hypercalcemia and vitamin D analogue should be administered early to avoid increased medication costs. On the other hand, this strategy symptomatic hypocalcaemia. Intermediate or subnormal might lead to inadequate treatment in patients with severe symptomatic hypocalcaemia as oral calcium alone may not PTH level is a less accurate predictor of hypocalcaemia. In that case, oral calcium should commence or patients should fully correct the hypocalcemia and so vitamin D supplements be monitored with serial calcium levels for the need of is indicated in such situation [36]. On the other hand, inpatient serial close monitoring of calcium and/or vitamin D analogue [42]. Therefore, PTH serum calcium is recommended after total thyroidectomy assay can now be considered as a perioperative adjunct to because most symptomatic hypocalcemia occurs around 24– predict normocalcaemia or hypocalcaemia with reasonable 28 hours after surgery [37]. A 24-hour or longer hospital accuracy. It can facilitate early discharge, avoid routine stay is invariably required. Therefore, efforts aremadeto calcium replacement, facilitate early calcium replacement to shorten hospital stays, decrease biochemical blood tests, avoid symptomatic hypocalcaemia and decrease overall cost and reduce hospital costs by adopting other strategies to as well as increase patients’ satisfaction. achieve early prediction of postthyroidectomy hypocalcemia. With the availability of IOPTH and wide application in patients undergoing minimally invasive parathyroidectomy 6. Conclusions to predict postoperative cure, this new surgical adjunct has been applied to thyroid surgery to monitor parathyroid New technologies have undoubtedly had a positive impact on function and to predict the occurrence of postoperative the surgical management of thyroid cancer. The application normocalcaemia or hypocalcaemia. 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