Our study demonstrated the safety and feasibility of IONM in patients undergoing MIE. However, the incidence of RLN paresis remained relatively high in spite of IONM, and might be related to the learning curve associated with the technique.
Minimally invasive surgery is currently the standard of care for esophageal cancer, based on the results of the randomized trials showing significant reduction in complications.(11–13). In both the TIME and MIRO trials, only a standard infracarinal two-field lymphadenectomy was performed. Retrospective studies published have shown that an extended lymphadenectomy is possible thoracoscopically and robotically(15, 16) ) with good short term outcomes. But, the rate of RLN paresis/paralysis remains high (15–30%)(17, 18). A recent nationwide database review in Japan, showed high rates of RLN palsy and pulmonary complications after thoracoscopic esophagectomies (19),. Hence, there is a need to reduce the RLN palsy rate to improve outcomes after MIE.
The value of an extended radical lymphadenectomy including a cervical field, in esophageal cancer surgery is still being debated. Nishihara et al(2) demonstrated an 18% survival improvement in patients who had undergone a three-field esophagectomy, without significant increase in morbidity compared to a standard two-field approach. Recent randomized data from China(20) has demonstrated no significant difference in OS or DFS in a cohort of 400 patients between two and three field lymphadenectomies. However, in this trial, patients in the two-field arm underwent a total mediastinal lymphadenectomy and hence these results may not be generalizable. A recently published meta-analysis by Bona et a(21)l showed an improved trend for 5-year overall survival with a three-field lymphadenectomy. When there is obvious nodal disease on imaging in the upper mediastinum and the neck, a three-field lymphadenectomy still remains the standard of care. We have just finished accrual of 700 patients in a randomized controlled trial comparing two field versus three field lymphadenectomy in patients without superior mediastinal nodes (NCT-00193817) and the long term and survival results of this study are awaited(22).
One of the common complications after a radical three-field lymphadenectomy is injury or traction on the recurrent laryngeal nerves resulting in temporary or permanent vocal cord palsy. Vocal cord paralysis/paresis results in significant morbidity and deterioration in quality of life(7). Immediate concerns are an increased risk of aspiration pneumonia and need for a tracheostomy(23). Apart from this, there is a significant increase in pulmonary complications and need for prolonged mechanical ventilation(7, 24). In the long term, untreated vocal cord paralysis leads to hoarseness of voice and difficulty in swallowing. Hence, all necessary precautions need to be employed to prevent injury to the RLN.
Intra-operative nerve monitoring was first introduced in the 1930s by neurosurgeons, but it was not until the 1980s that IONM became mainstream with introduction of commercially available nerve monitors(25). Due to technical difficulties and need for longer probes, IONM was not routinely employed in the thorax until the turn of the millenium. Hemmerling et al(26) first described the use of IONM for esophagectomies in 2001, when they used a double lumen endotracheal tube with a surface electrode, and were able to achieve successful lung isolation while being able to satisfactorily monitor the nerve. This was followed by various case series demonstrating the feasibility and efficacy of IONM during open esophagectomies (27–30). Takeda et al(9) have demonstrated the efficacy of IONM during thoracoscopic esophagectomy. They reported a 5.1% reduction in the nerve palsy rate with the crude data and 14.9% reduction after propensity matching. A systematic review by Wang et al(31) demonstrated that these studies showed a significant decrease in the rate of hoarseness of voice between the IONM and non-IONM groups(OR 0.14, 95%CI 0.03–0.63,p < 0.05) and a significant increase in the number of nodes dissected (mean-diff 4.30, 95% CI 2.75–5.85,p < 0.001). Our study demonstrated a nerve palsy rate of 31.3%, which is higher than reported by other studies (5–45%). This can be attributed to the learning curve associated with the procedure. The average number of nodes dissected in our study was around 43 nodes, which is comparable to other similar studies. In our unit, all patients undergo vocal cord examination after a three-field esophagectomy irrespective of the quality of their voice, this could have also resulted in a higher nerve palsy rate. We compared theses results to our historical cohort of patients who underwent MIE with three field lymphadenectomy, there was a reduction in the nerve palsy rate, but this was not statistically significant
Though most studies have demonstrated a reduction in the incidence of nerve palsies, this has not been found to be statistically significant when compared to visual inspection alone. On reviewing the data available on IONM, the use of IONM has not definitely proven to reduce complications whether in thyroid or esophageal surgeries(8, 31). However most studies have been single institution cohorts with limited number of patients. Some authors hypothesize that low volume surgeons tend to benefit more from IONM(32) than high-volume surgeons, but more data is needed to substantiate this claim.
One of the problems with IONM is that, despite signals being present at the end of the procedure on the nerve monitor, a significant number of patients (8/54- Hikage et al(28). and 9/60- Takeda et al(9).) went onto develop vocal cord paresis/paralysis. Hence, the pooled sensitivity of IONM remained low at a maximum of 66.7%. This is also reflected in our data, where four of five patients who developed a vocal cord palsy postoperatively had intact signals on IONM at the end of surgery. This may be due to the nerve remaining anatomically intact, but having some reduction in physiologic function(neuropraxia). Long term follow up data is needed to evaluate if these patients recover vocal cord function
Intra-operative nerve monitoring poses difficulties during minimally invasive surgery. Longer probes are required to simulate the nerves; sometimes, even with longer probes, the angles are difficult to negotiate to be able to make contact with the nerve. During robotic surgeries, the same problems exist, which are compounded by the fact that the bed-side assistant has to handle the IONM probe. These problems can however be minimized with experience. The magnification and better resolution provided by current technology can help in better visualization of the nerves and permit the dissection of more lymph nodes in the mediastinum.
Conduct of intraoperative nerve monitoring during esophagectomy requires few modifications in the anesthesia technique. First, since neuromuscular blockade is not used during the surgery, there may be few episodes of spontaneous breathing, coughing or patient movement during the surgery. In addition, the minimum alveolar concentration of inhalational anesthetic agents needs to be less than 1.0 to prevent the suppression of evoked potentials. In such cases, an additional infusion of intravenous anesthetic like propofol and remifentanil is used to maintain depth of anesthesia and to depress the laryngeal reflexes. Bi-spectral index guided titration of propofol infusion reduces the incidence of delayed recovery and haemodynamic instability associated with propofol infusion(33). Second, the device for airway management should be chosen wisely especially for minimally invasive surgeries. A double-lumen tube with surface embedded electrodes or a bronchial blocker through an electrode-embedded endotracheal tube should be ideally used for lung isolation. The position of the lung isolation device and surface electrodes must be confirmed after changing the position of the patient.
All our patients underwent intermittent nerve monitoring. Continuous nerve monitoring was attempted initially, but we faced a number of issues. It required a cervical-first approach, which led to a significant increase in operative time. Once the patient position was changed, the electrodes placed on the vagus sometimes tended to get displaced. Hence, for practical reasons we adopted the intermittent method.
The use of intra-operative nerve monitoring logically seems useful as the surgeon can be more confident of the anatomy, especially in cases with high nodal burden, anatomical variations and salvage esophagectomies. The lymph node yield has shown to be higher, this has been demonstrated previously and re-confirmed in our study. Another area, where nerve monitoring can be extremely useful is when there is variant anatomy such as a non-recurrent laryngeal nerve or an aberrant subclavian artery, in these cases the usual landmarks for visual identification are absent and hence nerve monitoring has been demonstrated to be helpful to identify and preserve the recurrent nerve(34, 35).
While IONM technology continues to evolve, our study has demonstrated its safety and feasibility in MIE, both VATS as well as robot- assisted. IONM can be used without a significant increase in operative time or post-operative complications. However, our study has some limitations. First, the technique failed to show a marked reduction in the incidence of RLN paresis. One of the inherent problems with IONM seems to be that there is a possibility of RLN paresis with an anatomically intact nerve resulting in signals being maintained till the end of the procedure in spite of functional paresis. Second, the sample size in our study is relatively small; nevertheless, it remains one of the larger studies done so far in patients undergoing MIE. Larger, well conducted, preferably randomized trials are needed to answer the question regarding its role in markedly reducing vocal cord paresis or palsy.