Che-Wei Wu

The mechanism of recurrent laryngeal nerve injury during thyroid surgery—The application of intraoperative neuromonitoring

BACKGROUND Identification of recurrent laryngeal nerve (RLN) has decreased the rates of permanent RLN palsy during thyroid operations; however, unexpected RLN palsy still occurs, even though the visual integrity was assured and most nerve injuries were not recognized intraoperatively. The aim of this study is to determine the causes of RLN palsy and to identify potentially reversible causes of RLN injury during the operation with the application of intraoperative neuromonitoring (IONM). METHODS One hundred and thirteen patients with 173 nerves at risk were enrolled in this study. All operations were performed by the same surgeon. The 4-step procedure of IONM was designed to obtain electromagnetic (EMG) signals from the vagus nerve and RLN before and after resection of thyroid lobe. RESULTS Sixteen nerves had loss of EMG signals after thyroid dissection, and the causes of nerve injuries were well elucidated with the application of IONM. One nerve injury was caused by inadvertent transection, which led to permanent RLN palsy. Among the remaining 15 nerves, 1 injury was caused by a constricting band of connective tissue, which was detected precisely and released intraoperatively, 2 by inadvertent clamping of the nerve, and 12 by apparent overstretching at the region of Berrys ligament. (Five nerves regained signals before closing the wound, but 1 showed impaired cord movement. Another 7 nerves did not regain signals before closing the wound, and all developed temporary RLN palsy.) CONCLUSIONS Our 4-step procedure of IONM is useful and helpful in elucidating the potential operative pitfalls during dissection near the RLN. Although the rates of RLN palsy were not decreased in this study, the use of neuromonitoring provided instructive information for future operations by ascertaining where and how the RLN has been injured.

Standardization of Intraoperative Neuromonitoring of Recurrent Laryngeal Nerve in Thyroid Operation

BackgroundThe lack of standardized procedures of intraoperative neuromonitoring (IONM) during thyroid operations may lead to highly variable results, and many of these results can cause misleading information and, conversely, increase the risk of recurrent laryngeal nerve (RLN) injury. Therefore, standardization of IONM procedures is necessary.MethodsA total of 289 patients (435 nerves at risk) who underwent thyroidectomy by the same surgeon were enrolled in this study. Each patient was intubated with EMG endotracheal tube by the same anesthesiologist. Standardized IONM procedures were applied in each patient. The procedures include preoperative and postoperative video-recording of vocal cord movement, ensuring the correct position of electrodes after the neck was placed at full extension, vagal stimulation and registration of EMG signals before and after RLN dissection, and photographic documentation of the exposed RLN.ResultsFive patients encountered dysfunction of IONM, which was caused by malposition of electrodes and the problem was detected at once. One patient with non-RLN was detected at the earlier stage of operation. Eighteen nerves experienced loss of EMG signals during thyroid dissection, and the causes of nerve injuries were well elucidated with the application of our standardized IONM procedures.ConclusionsThe standardized IONM procedures are useful and helpful not only to eliminate false IONM results, but also to elucidate the mechanism of RLN injury. After ascertaining the surgical pitfalls and improving the surgical techniques, the palsy rate was significantly reduced in this study.

Association between polymorphisms in DNA base excision repair genes XRCC1, APE1, and ADPRT and differentiated thyroid carcinoma.

Purpose: DNA BER pathway is related with carcinogenesis. We hypothesized that functional polymorphisms of three BER genes, XRCC1, apurinic/apyrimidinic endonuclease (APE1), and ADPRT, confer risks for DTC and its progression. Experimental Design: Five common nonsynonymous single nucleotide polymorphisms (Arg194Trp, Arg280His, and Arg399Gln for XRCC1; Asp148Glu for APE1; and Val762Ala for ADPRT) were genotyped in Chinese DTC cases and controls. Results: The XRCC1-194Trp/Trp genotype showed a significantly increased risk for DTC (odds ratio, 1.85; 95% confidence interval, 1.11-3.07; P = 0.018). Subset analysis based on regional LN metastasis showed that the genetic effect came primarily from the subjects with LN metastasis (odds ratio, 4.54; 95% confidence interval, 2.11-9.79; P = 0.0001), but no significant association for subjects without LN metastasis. The other four single nucleotide polymorphisms did not show significant results. Haplotype analysis of XRCC1 polymorphisms yielded a significant result (P = 0.004), especially in the subjects with LN metastasis (P = 0.0002). Moreover, we found that XRCC1-194Trp and ADPRT-762Ala variants collectively contributed to an increased risk of the disease and LN metastasis, with the combined variant homozygotes exhibiting the highest 3.18-fold risk for DTC (P = 0.046) and 9.25-fold risk for DTC with LN metastasis (P = 0.004). Conclusions: The XRCC1 polymorphisms, especially the 194Trp allele, may have an effect on DTC development and progression. This variant can interact with ADPRT-762Ala variant to further substantially increase susceptibility to the disease and regional LN metastasis. Identifying these risk genetic markers could provide more insight into the DTC pathogenesis and may also provide information to develop better prevention and therapeutic strategies.

Intraoperative neuromonitoring for the early detection and prevention of RLN traction injury in thyroid surgery: A porcine model

BACKGROUND Operative traction of the thyroid lobe is a necessary component of thyroid surgery. This surgical maneuver can cause traction injury of the recurrent laryngeal nerve (RLN), and this complication has been reported to be the most common mechanism of nerve injury. The goal of this study was to investigate the electromyographic (EMG) signal pattern during an acute RLN traction injury and establish reliable strategies to prevent the injury using intraoperative neuromonitoring (IONM). METHODS Fifteen piglets (30 RLNs) underwent IONM via automated periodic vagal nerve stimulation and had their EMG tracings recorded and correlated with various models of nerve injury. RESULTS In the pilot study, a progressive, partial EMG loss was observed under RLN tractions with different tension (n = 8). The changes in amplitudes were more marked and consistent than were the changes in latency. The EMG gradually gained partial recovery after the traction was relieved. Among the nerves injured with electrothermal (n = 4), clamping (n = 1), and transection (n = 1) models, the EMG showed immediate partial or complete loss, and no gradual EMG recovery was observed. Another 16 RLNs were used to investigate the potential of EMG recovery after different extents of RLN traction. We noted the EMG showed nearly full recovery if the traction stress was relieved before the loss of signal (LOS), but the recovery was worse if prolonged or repeated traction was applied. The mean restored amplitudes after the traction was relieved before, during, and after the LOS were 98 ± 3% (n = 6), 36 ± 4% (n = 4), and 15 ± 2% (n = 6), respectively. CONCLUSION RLN traction injury showed graded, partial EMG changes; early release of the traction before the EMG has degraded to LOS offers a good chance of EMG recovery. IONM can be used as a tool for the early detection of adverse EMG changes that may alert surgeons to correct certain maneuvers immediately to prevent irreversible nerve injury during the thyroid operation.

Anatomical Variations of Recurrent Laryngeal Nerve During Thyroid Surgery: How to Identify and Handle the Variations With Intraoperative Neuromonitoring

Recurrent laryngeal nerve (RLN) palsy is the most common and serious complication after thyroid surgery. Visual identification of the RLN during thyroid surgery has been shown to be associated with lower rates of palsy, and although it has been recommended as the gold standard for RLN treatment, it does not guarantee success against postoperative vocal cord paralysis. Anatomical variations of the RLN, such as extra‐laryngeal branches, distorted RLN, intertwining between branches of the RLN and inferior thyroid artery, and non‐recurrent laryngeal nerve, can be a potential cause of nerve injury due to visual misidentification. Therefore, intraoperative verification of functional and anatomical RLN integrity is a prerequisite for a safe thyroid operation. In this article, we review the literature and demonstrate how to identify and handle the anatomical variations of the RLN with the application of intraoperative neuromonitoring in the form of high resolution photography, which can be informative for thyroid surgeons. Anatomical variations of the RLN cannot be predicted preoperatively and might be associated with higher rates of RLN injury. The RLN injury caused by visual misidentification can be rare if the nerve is definitely identified early with intraoperative neuromonitoring.

Investigation of optimal intensity and safety of electrical nerve stimulation during intraoperative neuromonitoring of the recurrent laryngeal nerve: a prospective porcine model.

Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) has recently been more frequently applied in thyroid surgery. However, concerns have been raised regarding the safety and optimal intensity of electrical nerve stimulation.

Intraoperative neuromonitoring for early localization and identification of recurrent laryngeal nerve during thyroid surgery.

Early and definite identification of the recurrent laryngeal nerve (RLN) is an important step to avoid inadvertent nerve injury during complicated thyroid operations. This study aimed to determine the feasibility of routine use of intraoperative neuromonitoring (IONM) to localize and identify the RLN at an early stage of thyroid surgery. This prospective study enrolled 220 consecutive patients (333 RLNs at risk) who underwent thyroid operations with application of IONM. The RLN was localized and identified routinely with a nerve stimulator after opening the space between the thyroid and carotid sheath. The success rates of early RLN localization and identification were evaluated. The current for localization and the amplitude of evoked laryngeal electromyographic signals were also recorded and analyzed. All RLNs, including 87 (26%) nerves that were regarded as difficult to identify, were successfully localized and identified. The stimulation level for RLN localization was 2mA in 315 nerves (95%) and 3mA in the other 18 nerves (5%). The signal obtained from RLN localization (amplitude = 932 ±436μV) showed a clear and reliable laryngeal electromyographic response that was similar to that from direct vagus (amplitude=811±389μV) or RLN stimulation (amplitude=1132±472μV). The palsy rate was 0.6% and no permanent palsy occurred. RLN injury is rare if the nerve is definitely identified early in the thyroid operation. The conclusion of this study is that IONM is a reliable tool for early RLN localization and identification, even in complicated thyroid operations.

Does extensive dissection of recurrent laryngeal nerve during thyroid operation increase the risk of nerve injury? Evidence from the application of intraoperative neuromonitoring

PURPOSE Extensive dissection of recurrent laryngeal nerve (RLN) is inevitable in some complicated thyroid operations. The study aimed to determine whether extensive dissection of RLN increases the risk of nerve injury. METHOD Three hundred thirty-one patients (506 nerves at risk) who underwent thyroid operations with intraoperative neuromonitoring were included. The study chiefly focused on the 101 RLNs on which extensive nerve dissection from the thoracic inlet to the entry of larynx was performed and for which the nerve exposure was longer than 5 cm. Electromyographic (EMG) signals were obtained from the RLN and vagus nerve before and after complete RLN dissection, and these were defined as R(1), V(1) and R(2), V(2) signals, respectively. The RLN palsy rates and the change of EMG signals were evaluated and analyzed. RESULTS Among 101 nerves with extensive dissection, 13 nerves were due to the operation for recurrent goiter; 41 nerves, for large goiter with substernal extension; and 47 nerves, for thyroid cancer with paratracheal nodal metastasis. No permanent palsy occurred, but 2 nerves experienced loss of EMG signal after complete RLN dissection from a large recurrent goiter and developed temporary palsy. The palsy rates were 2% (2/101) in the extensive dissection group and 2.5% (10/405) in the nonextensive dissection group (P = .77). Among 99 nerves with normal vocal function after operation, none experienced weakened signal after complete RLN dissection, and the mean amplitudes of R(2) and V(2) signals were not significantly different from those of R(1) and V(1) signals (R(2) vs R(1); 1038 vs 1030 μV; P = .74; V(2) vs V(1); 824 vs 816 μV; P = .75). CONCLUSIONS The results of this study suggest that careful surgical dissection is well tolerated by the RLN.

Vagal nerve stimulation without dissecting the carotid sheath during intraoperative neuromonitoring of the recurrent laryngeal nerve in thyroid surgery

Vagal nerve stimulation (VNS) has been recommended as a routine procedure during intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN). However, many surgeons have been discouraged from performing VNS because of the need for opening the carotid sheath. The purpose of this study was to investigate the feasibility and reliability of VNS without carotid sheath dissection.

Detecting and identifying nonrecurrent laryngeal nerve with the application of intraoperative neuromonitoring during thyroid and parathyroid operation

PURPOSE The nonrecurrent laryngeal nerve (NRLN) is a rare anatomical variant but associated with high risk of nerve injury during thyroid and parathyroid operations. Therefore, intraoperative detection and verification of NRLN are necessary. METHOD A total of 390 consecutive patients who underwent thyroid and parathyroid operations (310 RLNs dissected on the right side and 293 nerves on the left side) were enrolled. Electrically evoked electromyography was recorded from the vocalis muscles via an endotracheal tube with glottis surface recording electrodes. At an early stage of operation, vagal nerve was routinely stimulated at the level of inferior thyroid pole to ensure normal path of RLN. If there is a negative response from lower position but positive response from upper vagal stimulation, it indicates the occurrence of a NRLN, and we localize its separation point and path. RESULTS Four right NRLNs (1.3%) without preoperative recognition were successfully detected at an early stage of operation. Three patients were operated on for thyroid disease, one for parathyroid adenoma and all were associated with right aberrant subclavian artery. All NRLNs were localized and identified precisely with intraoperative neuromonitoring. Functional integrity of all nerves was confirmed by the intraoperative neuromonitoring and postoperative laryngeal examination. CONCLUSIONS Vagal stimulation at the early stage of operation is a simple, useful, and reliable procedure to detect and identify the NRLN.