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Background:
Systematic Review

Application of Intraoperative Neuromonitoring (IONM) of the Recurrent Laryngeal Nerve during Esophagectomy: A Systematic Review and Meta-Analysis

by
Boyang Chen
1,†,
Tianbao Yang
1,†,
Wu Wang
1,†,
Weifeng Tang
2,
Jinbiao Xie
1,* and
Mingqiang Kang
1,3,*
1
Department of Cardiothoracic Surgery, The Affiliated Hospital of Putian University, Putian 351100, China
2
Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
3
Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Clin. Med. 2023, 12(2), 565; https://doi.org/10.3390/jcm12020565
Submission received: 12 November 2022 / Revised: 24 December 2022 / Accepted: 5 January 2023 / Published: 10 January 2023
(This article belongs to the Special Issue Esophagectomy and Non-esophagectomy: Different Treatment Strategies on Esophageal Cancer)
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Abstract

:
Background: recurrent laryngeal nerve palsy (RLNP) is a common and severe complication of esophagectomy in esophageal cancer (EC). Several studies explored the application of intraoperative neuromonitoring (IONM) in esophagectomy to prevent RLNP. The purpose of this study was to conduct a systematic review and meta-analysis to evaluate the value of IONM in esophagectomy for EC. Methods: an electronic of the literature using Google Scholar, PubMed, Embase, and Web of Science (data up to October 2022) was conducted and screened to compare IONM-assisted and conventional non-IONM-assisted esophagectomy. RLNP, the number of mediastinal lymph nodes (LN) dissected, aspiration, pneumonia, chylothorax, anastomotic leakage, the number of total LN dissected, postoperative hospital stay and total operation time were evaluated using Review Manager 5.4.1. Result: ten studies were ultimately included, with a total of 949 patients from one randomized controlled trial and nine retrospective case–control studies in the meta-analysis. The present study demonstrated that IONM reduced the incidence of RLNP(Odds Ratio (OR) 0.37, 95% Confidence Interval (CI) 0.26–0.52) and pneumonia (OR 0.58, 95%CI 0.41–0.82) and was associated with more mediastinal LN dissected (Weighted Mean Difference (WMD) 4.75, 95%CI 3.02–6.48) and total mediastinal LN dissected (WMD 5.47, 95%CI 0.39–10.56). In addition, IONM does not increase the incidence of aspiration (OR 0.4, 95%CI 0.07–2.51), chylothorax (OR 0.55, 95%CI 0.17–1.76), and anastomotic leakage (OR 0.78, 95%CI 0.48–1.27) and does not increase the total operative time (WMD −12.33, 95%CI −33.94–9.28) or postoperative hospital stay (WMD −2.07 95%CI −6.61–2.46) after esophagectomy. Conclusion: IONM showed advantages for preventing RLNP and pneumonia and was associated with more mediastinal and total LN dissected in esophagectomy. IONM should be recommended for esophagectomy.

1. Introduction

The recurrent laryngeal nerve (RLN) lymph node (LN) is the most frequent site of LN metastasis in esophageal cancer (EC) and an important prognostic factor for EC [1,2,3]. Routinely, the lymphadenectomy of RLN LN is one of the critical steps in the esophagectomy of EC and is very important for accurate staging and the improvement of long-term survival [4,5].
However, despite the oncologic benefits, RLN LN dissection is a highly invasive procedure. Recurrent laryngeal nerve palsy (RLNP) may be caused by thermal injury, stretching, compression, or vascular compromise to RLN due to its deep anatomical location and poor visualization, with a reported incidence of 9–22% [6,7,8]. In Asia, the incidence of RLNP can be up to 59%, mainly attributed to extensive three-field lymph node dissection [9]. Patients with RLNP often suffer from hoarseness, aspiration, pneumonia, and dyspnea, which can be even more fatal in those who undergo esophagectomy [10]. Due to the risk of adverse outcomes described, some surgeons have even had to compromise between these complications and long-term survival [11].
Intraoperative neuromonitoring (IONM) detects the stimulation of the RLN by sensing the electromyographic signal of vocal muscle movement, which helps to identify the RLN and properly reduces medically induced injuries [12]. IONM has gained wide acceptance and has become an adjunct to the gold standard of visually identifying RLN and reducing RLN injury in thyroid and parathyroid surgery [13]. In 2001, Hemmerling et al. first reported the application of IONM in esophagectomy [14]. In the following decades, several studies have further explored the application of IONM in esophagectomy; however, the results are controversial. Therefore, the purpose of this study was to conduct a systematic review and meta-analysis to evaluate the value of IONM in esophagectomy for EC.

2. Materials and Methods

2.1. Literature Search

A systematic review and data synthesis were conducted according to a pre-defined, registered (PROSPERO, CRD42022354833) and published protocol following PRISMA 2020 statement [15]. The systematic literature searches of Google Scholar, PubMed, Embase, and Web of Science databases were performed using terms comprising “esophagectomy”, “esophagus”, “esophageal”, “intraoperative”, “nerve monitoring”, “neuromonitoring”, “neural monitoring”, “IONM”, and “nerve detector” with the Boolean operators “AND” or “OR” (data up to 31 October 2022). In the first stage, all the literature was screened by title and abstract. In the second stage, potentially eligible examples of the literature were reviewed in their full text to determine eligibility for inclusion-exclusion criteria. The literature search and review were performed independently and duplicated by two reviewers. References from the eligible literature were further checked for additional suitable studies. Any disagreement was resolved through discussion. The reasons for exclusion were recorded.

2.2. Inclusion-Exclusion Criteria

Inclusion criteria included: (1) Studies comparing IONM-assisted and conventional non-IONM-assisted esophagectomy. (2) Patients with esophageal malignancy who underwent esophagectomy combined with mediastinal lymph node dissection. Exclusion criteria included: (1) Conference abstracts, review articles, and case reports. (2) Non-comparative studies.

2.3. Outcomes of Interest

The primary outcome measures were postoperative complications, including RLNP and the number of mediastinal LN resected. Secondary outcome measures were the total LN resected, total operation time, postoperative hospital stay (POHS), and other postoperative complications such as pneumonia, hoarseness, aspiration, chylothorax, and anastomotic leakage.

2.4. Data Extraction and Assessment of Methodological Quality

Data regarding participant characteristics included the study design, author, the number of participants, surgical details, operation time, POHS, and postoperative complications. For some outcomes, data were recorded as medians with quartiles or ranges, and an online conversion tool www.math.hkbu.edu.hk/~tongt/papers/median2mean.html (accessed on 25 December 2022) was used to convert the data to means and standard deviations (SD) [16,17]. The Cochrane risk-of-bias tool was used to assess RCTs and the Newcastle–Ottawa quality assessment scale (NOS) for non-RCTs.

2.5. Statistical Analysis

Statistical analysis and plotting were performed using Review Manager 5.4.1 (Cochrane Collaboration, Oxford, UK). Dichotomous variables from the relevant studies were extracted, and the corresponding pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Mantel–Haenszel method. For continuous variables, the weighted mean differences (WMDs) with 95% CIs were calculated by the inverse variance method. A random effects model was applied to make the statistical results more reliable and appropriately conservative [18]. Higgins’ I2 statistic was used to determine the percentage of total variations across the studies due to heterogeneity. Publication biases were assessed when the number of included studies was greater than 10. The publication bias was qualitatively estimated using funnel plots. The Egger test was conducted to evaluate the publication bias when the funnel plot was visually inspected as asymmetry, and the “trim and fill” test was further accessed if the publication bias was detected [19].

2.6. Ethics Statement

This study is a meta-analysis based on publicly available data and does not include human subjects or require Institutional Review Board (IRB) approval.

3. Result

3.1. Identification of Studies and Characteristics

A total of 106 references that were considered potentially relevant were screened from PubMed, EMBASE, and Web of Science. Through the screening of titles and abstracts, 39 papers were identified for full-text review, and 10 studies that met the inclusion-exclusion criteria were ultimately included in this study. The literature screening process is shown in Figure 1. This meta-analysis contained nine retrospective case–control studies and one randomized control trial [20,21,22,23,24,25,26,27,28,29]. A total of 949 patients were included in the study, of which 508 patients were treated with IONM, and 441 patients were the non-IONM control. The characteristics of the included studies are summarized in Table 1. The literature quality assessment of each study included in the analysis is summarized. (Supplementary Table S1).

3.2. RLNP

RLNP was reported in all 10 studies and occurred in a total of 214 among 949 patients. The Forest plot is shown in Figure 2. The Pooled analysis shows that IONM is associated with a reduced incidence of RLNP after esophagectomy (OR = 0.32, 95%CI (0.19, 0.54), p = 0.08; I2 = 42%). A sensitivity analysis was further performed as I2 was close to 50%. The results of the pooled analysis remained robust after omitting any of the included studies. (Supplementary Table S2). The funnel plot showed asymmetry visually, and Egger’s test showed a significant publication bias. (Egger’s test, p = 0.02) The “Trim and Fill” test was further accessed, and no trimming was performed, which showed that the result was robust.

3.3. Number of Mediastinal LN Dissected

The number of mediastinal LN dissected was reported in three studies among 340 patients. The Forest plot is shown in Figure 3. The Pooled analysis showed that IONM was associated with significantly more mediastinal LN dissected after esophagectomy (WMD = 4.26, 95%CI (1.63, 6.89), p = 0.14; I2 = 49%). The sensitivity analysis showed that the results of the pooled analysis were not statistically significantly different after omitting Luo Zhao’s study. (Supplementary Table S3).

3.4. Aspiration

Aspiration was reported in three studies and occurred in a total of 68 among 227 patients. The Forest plot is shown in Figure 4. The Pooled analysis showed no statistical difference between IONM and the incidence of aspiration (OR = 0.4, 95%CI (0.07, 2.51) 0.004, I2 = 82%). Sensitivity analysis showed a decreased incidence of aspiration after omitting Makoto Hikage’s study. (Supplementary Table S4).

3.5. Pneumonia

Pneumonia was reported in nine studies and occurred in a total of 172 among 889 patients. The Forest plot is shown in Figure 5. The Pooled analysis showed that IONM is associated with a reduced incidence of pneumonia (OR = 0.57, 95%CI (0.34, 0.97), p = 0.05, I2 = 48%). The sensitivity analysis showed that the results remained robust after omitting any of the included studies. (Supplementary Table S5).

3.6. Chylothorax

Chylothorax was reported in four studies and occurred in a total of 10 among 434 patients. The Forest plot is shown in Figure 6. The Pooled analysis showed no statistical difference between IONM and the incidence of chylothorax (OR= 0.53, 95%CI (0.12, 2.32), p = 0.36, I2 = 6%). The sensitivity analysis showed that the results remained robust after omitting any of the included studies. (Supplementary Table S6).

3.7. Anastomotic Leakage

Anastomotic leakage was reported in six studies and occurred in a total of 82 among 708 patients. The Forest plot is shown in Figure 7. The Pooled analysis showed no statistical difference between IONM and the incidence of anastomotic leakage (OR = 0.78, 95%CI (0.48, 1.28), p = 0.67, I2 = 0%). The sensitivity analysis showed that the results remained robust after omitting any of the included studies. (Supplementary Table S7).

3.8. Number of Total LN Dissected

The number of total LN dissected was reported in three studies among 377 patients. The Forest plot is shown in Figure 8. The Pooled analysis showed that IONM was associated with a significantly higher total LN dissected after esophagectomy (WMD = 5.47 95%CI (0.39, 10.56) p = 0.03; I2 = 62%). The sensitivity analysis showed that the results of the pooled analysis were not statistically or significantly different after omitting Masami Yuda and D. Zhong’s study. (Supplementary Table S8).

3.9. Postoperative Hospital Stay (POHS)

POHS was reported in three studies among 568 patients. The Forest plot is shown in Figure 9. The Pooled analysis showed no statistical difference between IONM and POSH after esophagectomy (WMD = −2.07 95%CI (−6.61, 2.46) p = 0.10; I2 = 56%). The sensitivity analysis showed a decreased POHS after omitting Chang-Lun Huang’s study. (Supplementary Table S9).

3.10. Total Operation Time

The total operation time was reported in three studies among 452 patients. The Forest plot is shown in Figure 10. The Pooled analysis showed no significant difference in the total operative time between the IONM and controls (WMD= −12.33, 95%CI (−33.94, 9.28) p = 0.09; I2 = 59%). The sensitivity analysis showed a decreased total operation time after omitting LuoZhao’s study. (Supplementary Table S10).

4. Discussion

The electrophysiological monitoring of RLN can be traced back to as early as 1966 by Shedd and Durham [30]. The commercially available endotracheal tube with surface electrodes for IONM was first reported in 1996 and soon gained wide recognition in thyroid and head and neck surgery [31]. According to a survey, more than half of the otolaryngologists and general surgeons have applied IONM in surgery [32,33]. A recent meta-analysis demonstrated that IONM significantly reduced the total injury of RLN in thyroidectomy. (RR = 0.68, 95%CI (0.55–0.83)) (12). Currently, the application of IONM in thyroid surgery has been recommended by various clinical guidelines [13,34,35].
RLN LN is also the most metastatic LN of thoracic esophageal squamous carcinoma. Although complete lymph node dissection significantly improved long-term survival for esophageal patients, the rise in comorbidities annoys surgeons, and it was reported that esophagectomy has a more than four times higher incidence of injury to RLN than thyroid surgery [36,37]. In 2001, Hemmerling first reported the application of IONM in a patient of esophageal cancer with extensive RLN LN involvement [14]. In 2010, Hans Gelpke reported the first prospective study of IONM for lobectomy and esophagectomy and confirmed its feasibility [38]. D. Zhong published the first comparative study of IONM in esophagectomy in 2014, which showed that IONM reduced the incidence of RLNP and pneumonia and improved the mediastinal LN resection [29]. In 2021, Xinxin Wang published the first meta-analysis of IONM in esophagectomy, including five retrospective studies, and suggested that IONM was associated with lower rates of RLNP and hoarseness and more effective lymphadenectomy [39].
Our meta-analysis included additional studies, and all were published within 10 years. These studies were all from East Asia, and the pathological type was mainly squamous cell carcinoma. Most studies used the McKeown procedure, except for the Sweet procedure (left thoracotomy) by D. Zhong and transhiatal esophagectomy by Shuhei Komatsu [20,29]. The Medtronic system was applied for IONM in all included studies. The laryngeal electromyography was monitored using a Medtronic NIM Contact Reinforced EMG Endotracheal tube, and the automatic periodic stimulation system used a Medtronic NIM-Response 3.0 with the APS Electrode system.
Our meta-analysis showed that IONM is associated with a reduced incidence of RLNP and more mediastinal and total LNs dissected. A variety of factors may be attributed to the advantages of IONM. Firstly, RLN can be easily identified by stimulation probes and thus avoid injury. Especially in patients who received neoadjuvant therapy, the fibrotic tissue after tumor regression in the upper mediastinum and poorly defined margins due to tissue edema is difficult to distinguish from RLN visually. IONM not only helps to identify RLN but also enhances the surgeon’s confidence [23]. Secondly, inappropriate traction on nerves is another mechanism that causes RLN injury. When the real-time alarm is triggered by inappropriate traction, the nerve injury can be transient if the surgeon releases the traction immediately [40]. Thirdly, the recently proposed concept of mesenteric excision suggests that the mesoesophagus in the upper mediastinum has potential lymphatic drainage and micro-metastases and should be removed radically [41]. The application of IONM fits with the mesenteric excision theory. RLN is wrapped in the mesoesophagus, and IONM helps predict the location of RLN before visual contact, which makes the dissection using an energy device adjacent to the RLN much safer and allows for the en-bloc resect of the mesoesophagus and LNs [26,42].
Although the Funnel plot and Egger’s test showed a significant publication bias, the “Trim and Fill” test proved that our results were still robust. IONM showed an obvious superiority in almost all studies. As Shuhei Komatsu stated in his article, “Because clinical benefit was obvious, it was not possible to have a group of patients without CNM(IONM) for comparison” [20]. IONM may be so stable and effective that there is a lack of negative results. Our study also revealed that IONM reduced the incidence of pneumonia. Postoperative pneumonia is the most common complication after esophagectomy, with an incidence of up to 60% [43]. Several recent studies showed that RLNP is associated with pneumonia, and multivariate analysis showed that RLNP is the primary independent risk factor for pneumonia. (RR = 2.3–6.2) [9,44]. Our study supports the previous studies that IONM can reduce pneumonia by preventing RLNP. Although inconsistent with a previous meta-analysis, our results are more reliable due to the larger number of studies included and insignificant heterogeneity [39]. A study suggests that RLNP is an independent prognostic factor for pneumonia and POHS [9]. In addition, we found that IONM does not increase the operative time and the risk of other common complications, which reflected the feasibility of IONM.
The present study has several limitations. First, all the included studies were not randomized control trials; therefore, bias was inevitable. Second, most of the studies are single-centered with relatively small sample sizes, and some studies used historical control groups. This limited the statistical power. Thirdly, this study lacks an analysis of the impact of IONM on postoperative survival. Finally, due to the heterogeneity in this study, the results are interpreted with caution.

5. Conclusions

Our meta-analysis demonstrated that the application of IONM during esophagectomy reduced the incidence of RLNP and pneumonia and was associated with more mediastinal and total LN dissected. In addition, IONM does not increase the incidence of aspiration, chylothorax, and anastomotic leakage and does not increase the total operative time or postoperative hospital stays. IONM should be recommended for esophagectomy. Large RCTs are still needed to provide more evidence in future studies.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm12020565/s1, Supplementary Table S1: Assessment of risk of bias in non-RCTs by Newcastle-Ottawa Quality Assessment Scale; Supplementary Table S2: Sensitivity Analysis of IONM for RLNP; Supplementary Table S3: Sensitivity Analysis of IONM for Number of mediastinal LN dissected. Supplementary Table S4: Sensitivity Analysis of IONM for Aspiration. Supplementary Table S5: Sensitivity Analysis of IONM for Pneumonia. Supplementary Table S6: Sensitivity Analysis of IONM for Chylothorax. Supplementary Table S7: Sensitivity Analysis of IONM for Anastomotic Leakage. Supplementary Table S8: Sensitivity Analysis of IONM for Total LN Dissected. Supplementary Table S9: Sensitivity Analysis of IONM for POHS. Supplementary Table S10: Sensitivity Analysis of IONM for Total Operation Time.

Author Contributions

B.C. wrote the paper; W.T., statistically analyzed and graphed; J.X. and M.K. administrative support. T.Y. and W.W. literature searched and screened. All authors read and approved the final version of the article. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data for this study are based on the published literature.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Wu, J.; Chen, Q.X.; Zhou, X.M.; Mao, W.M.; Krasna, M.J. Does recurrent laryngeal nerve lymph node metastasis really affect the prognosis in node-positive patients with squamous cell carcinoma of the middle thoracic esophagus? BMC Surg. 2014, 14, 43. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Baba, M.; Aikou, T.; Yoshinaka, H.; Natsugoe, S.; Fukumoto, T.; Shimazu, H.; Akazawa, K. Long-term results of subtotal esophagectomy with three-field lymphadenectomy for carcinoma of the thoracic esophagus. Ann. Surg. 1994, 219, 310–316. [Google Scholar] [CrossRef] [PubMed]
  3. Malassagne, B.; Tiret, E.; Duprez, D.; Coste, J.; de Sigalony, J.P.; Parc, R. Prognostic value of thoracic recurrent nerve nodal involvement in esophageal squamous cell carcinoma. J. Am. Coll. Surg. 1997, 185, 244–249. [Google Scholar] [CrossRef]
  4. Jamieson, G.G.; Lamb, P.J.; Thompson, S.K. The role of lymphadenectomy in esophageal cancer. Ann. Surg. 2009, 250, 206–209. [Google Scholar] [CrossRef] [PubMed]
  5. Yang, H.; Wang, J.; Huang, Q.; Zheng, Y.; Ela Bella, A.; Wang, R.; Fu, J.; Li, A.; Li, X. Intraoperative ultrasonography for the identification of thoracic recurrent laryngeal nerve lymph nodes in patients with esophageal cancer. Dis. Esophagus 2016, 29, 152–158. [Google Scholar] [CrossRef]
  6. Gockel, I.; Kneist, W.; Keilmann, A.; Junginger, T. Recurrent laryngeal nerve paralysis (RLNP) following esophagectomy for carcinoma. Eur. J. Surg. Oncol. 2005, 31, 277–281. [Google Scholar] [CrossRef]
  7. Taniyama, Y.; Miyata, G.; Kamei, T.; Nakano, T.; Abe, S.; Katsura, K.; Sakurai, T.; Teshima, J.; Hikage, M.; Ohuchi, N. Complications following recurrent laryngeal nerve lymph node dissection in oesophageal cancer surgery. Interact. Cardiovasc. Thorac. Surg. 2015, 20, 41–46. [Google Scholar] [CrossRef] [Green Version]
  8. Myssiorek, D. Recurrent laryngeal nerve paralysis: Anatomy and etiology. Otolaryngol. Clin. North Am. 2004, 37, 25–44. [Google Scholar] [CrossRef]
  9. Scholtemeijer, M.G.; Seesing, M.F.J.; Brenkman, H.J.F.; Janssen, L.M.; van Hillegersberg, R.; Ruurda, J.P. Recurrent laryngeal nerve injury after esophagectomy for esophageal cancer: Incidence, management, and impact on short- and long-term outcomes. J. Thorac. Dis. 2017, 9 (Suppl. S8), S868–S878. [Google Scholar] [CrossRef] [Green Version]
  10. Jeon, Y.J.; Cho, J.H.; Lee, H.K.; Kim, H.K.; Choi, Y.S.; Zo, J.I.; Shim, Y.M. Management of patients with bilateral recurrent laryngeal nerve paralysis following esophagectomy. Thorac. Cancer 2021, 12, 1851–1856. [Google Scholar] [CrossRef]
  11. Lagergren, J.; Mattsson, F.; Zylstra, J.; Chang, F.; Gossage, J.; Mason, R.; Lagergren, P.; Davies, A. Extent of Lymphadenectomy and Prognosis After Esophageal Cancer Surgery. JAMA Surg. 2016, 151, 32–39. [Google Scholar] [CrossRef] [PubMed]
  12. Bai, B.; Chen, W. Protective Effects of Intraoperative Nerve Monitoring (IONM) for Recurrent Laryngeal Nerve Injury in Thyroidectomy: Meta-analysis. Sci. Rep. 2018, 8, 7761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Randolph, G.W.; Dralle, H.; International Intraoperative Monitoring Study Group; Abdullah, H.; Barczynski, M.; Bellantone, R.; Brauckhoff, M.; Carnaille, B.; Cherenko, S.; Chiang, F.Y.; et al. Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: International standards guideline statement. Laryngoscope 2011, 121 (Suppl. S1), S1–S16. [Google Scholar] [CrossRef] [PubMed]
  14. Hemmerling, T.M.; Schmidt, J.; Jacobi, K.E.; Klein, P. Intraoperative monitoring of the recurrent laryngeal nerve during single-lung ventilation in esophagectomy. Anesth. Analg. 2001, 92, 662–664. [Google Scholar] [CrossRef]
  15. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  16. Wan, X.; Wang, W.; Liu, J.; Tong, T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol. 2014, 14, 135. [Google Scholar] [CrossRef] [Green Version]
  17. Luo, D.; Wan, X.; Liu, J.; Tong, T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat. Methods Med. Res. 2018, 27, 1785–1805. [Google Scholar] [CrossRef] [Green Version]
  18. Bell, A.; Fairbrother, M.; Jones, K. Fixed and random effects models: Making an informed choice. Qual. Quant. 2019, 53, 1051–1074. [Google Scholar] [CrossRef] [Green Version]
  19. Sterne, J.A.; Sutton, A.J.; Ioannidis, J.P.; Terrin, N.; Jones, D.R.; Lau, J.; Carpenter, J.; Rucker, G.; Harbord, R.M.; Schmid, C.H.; et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011, 343, d4002. [Google Scholar] [CrossRef] [Green Version]
  20. Komatsu, S.; Konishi, T.; Matsubara, D.; Soga, K.; Shimomura, K.; Ikeda, J.; Taniguchi, F.; Fujiwara, H.; Shioaki, Y.; Otsuji, E. Continuous Recurrent Laryngeal Nerve Monitoring During Single-Port Mediastinoscopic Radical Esophagectomy for Esophageal Cancer. J. Gastrointest. Surg. 2022, 26, 2444–2450. [Google Scholar] [CrossRef]
  21. Huang, C.L.; Chen, C.M.; Hung, W.H.; Cheng, Y.F.; Hong, R.P.; Wang, B.Y.; Cheng, C.Y. Clinical Outcome of Intraoperative Recurrent Laryngeal Nerve Monitoring during Thoracoscopic Esophagectomy and Mediastinal Lymph Node Dissection for Esophageal Cancer. J. Clin. Med. 2022, 11, 4949. [Google Scholar] [CrossRef] [PubMed]
  22. Zhao, L.; He, J.; Qin, Y.; Liu, H.; Li, S.; Han, Z.; Li, L. Application of intraoperative nerve monitoring for recurrent laryngeal nerves in minimally invasive McKeown esophagectomy. Dis. Esophagus 2022, 35, doab080. [Google Scholar] [CrossRef] [PubMed]
  23. Yuda, M.; Nishikawa, K.; Ishikawa, Y.; Takahashi, K.; Kurogochi, T.; Tanaka, Y.; Matsumoto, A.; Tanishima, Y.; Mitsumori, N.; Ikegami, T. Intraoperative nerve monitoring during esophagectomy reduces the risk of recurrent laryngeal nerve palsy. Surg. Endosc. Other Interv. Tech. 2022, 36, 3957–3964. [Google Scholar] [CrossRef] [PubMed]
  24. Takeda, S.; Iida, M.; Kanekiyo, S.; Nishiyama, M.; Tokumitsu, Y.; Shindo, Y.; Yoshida, S.; Suzuki, N.; Yoshino, S.; Nagano, H. Efficacy of intraoperative recurrent laryngeal neuromonitoring during surgery for esophageal cancer. Ann. Gastroenterol. Surg. 2021, 5, 83–92. [Google Scholar] [CrossRef] [PubMed]
  25. Fujimoto, D.; Taniguchi, K.; Kobayashi, H. Intraoperative neuromonitoring during prone thoracoscopic esophagectomy for esophageal cancer reduces the incidence of recurrent laryngeal nerve palsy: A single-center study. Updat. Surg. 2021, 73, 587–595. [Google Scholar] [CrossRef]
  26. Kobayashi, H.; Kondo, M.; Mizumoto, M.; Hashida, H.; Kaihara, S.; Hosotani, R. Technique and surgical outcomes of mesenterization and intra-operative neural monitoring to reduce recurrent laryngeal nerve paralysis after thoracoscopic esophagectomy: A cohort study. Int. J. Surg. 2018, 56, 301–306. [Google Scholar] [CrossRef] [PubMed]
  27. Zhu, W.; Yang, F.; Cao, J.; Zhao, C.; Dong, B.; Chen, D. Application of recurrent laryngeal nerve detector in the neck anastomosis of upper or middle-thoracic esophageal carcinoma. Cancer Res. Clin. 2018, 30, 233–236. [Google Scholar]
  28. Hikage, M.; Kamei, T.; Nakano, T.; Abe, S.; Katsura, K.; Taniyama, Y.; Sakurai, T.; Teshima, J.; Ito, S.; Niizuma, N.; et al. Impact of routine recurrent laryngeal nerve monitoring in prone esophagectomy with mediastinal lymph node dissection. Surg. Endosc. 2017, 31, 2986–2996. [Google Scholar] [CrossRef]
  29. Zhong, D.; Zhou, Y.; Li, Y.; Wang, Y.; Zhou, W.; Cheng, Q.; Chen, L.; Zhao, J.; Li, X.; Yan, X. Intraoperative recurrent laryngeal nerve monitoring: A useful method for patients with esophageal cancer. Dis. Esophagus 2014, 27, 444–451. [Google Scholar] [CrossRef]
  30. Shedd, D.P.; Durham, C. Electrical identification of the recurrent laryngeal nerve. I. Response of the canine larynx to electrical stimulation of the recurrent laryngeal nerve. Ann. Surg. 1966, 163, 47–50. [Google Scholar] [CrossRef]
  31. Eisele, D.W. Intraoperative electrophysiologic monitoring of the recurrent laryngeal nerve. Laryngoscope 1996, 106, 443–449. [Google Scholar] [CrossRef]
  32. Singer, M.C.; Rosenfeld, R.M.; Sundaram, K. Laryngeal nerve monitoring: Current utilization among head and neck surgeons. Otolaryngol. Head Neck Surg. 2012, 146, 895–899. [Google Scholar] [CrossRef] [PubMed]
  33. Deniwar, A.; Kandil, E.; Randolph, G. Electrophysiological neural monitoring of the laryngeal nerves in thyroid surgery: Review of the current literature. Gland Surg. 2015, 4, 368–375. [Google Scholar] [PubMed]
  34. Chandrasekhar, S.S.; Randolph, G.W.; Seidman, M.D.; Rosenfeld, R.M.; Angelos, P.; Barkmeier-Kraemer, J.; Benninger, M.S.; Blumin, J.H.; Dennis, G.; Hanks, J.; et al. Clinical practice guideline: Improving voice outcomes after thyroid surgery. Otolaryngol. Head Neck Surg. 2013, 148, S1–S37. [Google Scholar] [CrossRef] [PubMed]
  35. Diercks, G.R.; Rastatter, J.C.; Kazahaya, K.; Kamani, D.; Quintanilla-Dieck, L.; Shindo, M.L.; Hartnick, C.; Shin, J.J.; Singer, M.C.; Stack, B.C., Jr.; et al. Pediatric intraoperative nerve monitoring during thyroid surgery: A review from the American Head and Neck Society Endocrine Surgery Section and the International Neural Monitoring Study Group. Head Neck 2022, 44, 1468–1480. [Google Scholar] [CrossRef]
  36. Lo, C.Y.; Kwok, K.F.; Yuen, P.W. A prospective evaluation of recurrent laryngeal nerve paralysis during thyroidectomy. Arch. Surg. 2000, 135, 204–207. [Google Scholar] [CrossRef] [Green Version]
  37. Tsang, R.K.; Law, S. Adaptation of Continuous Intraoperative Vagus Nerve Stimulation for Monitoring of Recurrent Laryngeal Nerve During Minimally Invasive Esophagectomy. World J. Surg. 2016, 40, 137–141. [Google Scholar] [CrossRef]
  38. Gelpke, H.; Grieder, F.; Decurtins, M.; Cadosch, D. Recurrent laryngeal nerve monitoring during esophagectomy and mediastinal lymph node dissection. World J. Surg. 2010, 34, 2379–2382. [Google Scholar] [CrossRef]
  39. Wang, X.; Guo, H.; Hu, Q.; Ying, Y.; Chen, B. Efficacy of Intraoperative Recurrent Laryngeal Nerve Monitoring During Thoracoscopic Esophagectomy for Esophageal Cancer: A Systematic Review and Meta-Analysis. Front. Surg. 2021, 8, 773579. [Google Scholar] [CrossRef]
  40. Wong, I.Y.H.; Zhang, R.Q.; Tsang, R.K.Y.; Kwok, J.Y.Y.; Wong, C.L.Y.; Chan, D.K.K.; Chan, F.S.Y.; Law, S.Y.K. Improving Outcome of Superior Mediastinal Lymph Node Dissection During Esophagectomy: A Novel Approach Combining Continuous and Intermittent Recurrent Laryngeal Nerve Monitoring. Ann. Surg. 2021, 274, 736–742. [Google Scholar] [CrossRef]
  41. Tsunoda, S.; Shinohara, H.; Kanaya, S.; Okabe, H.; Tanaka, E.; Obama, K.; Hosogi, H.; Hisamori, S.; Sakai, Y. Mesenteric excision of upper esophagus: A concept for rational anatomical lymphadenectomy of the recurrent laryngeal nodes in thoracoscopic esophagectomy. Surg. Endosc. 2020, 34, 133–141. [Google Scholar] [CrossRef] [PubMed]
  42. Zhu, T.Y.; Deng, X.M.; Wang, G.J.; Gao, B.L.; Li, R.X.; Zhang, Y.F.; Wang, J.T. En bloc mesoesophageal esophagectomy through thoracoscopy combined with laparoscopy based on the mesoesophageal theory. Surg. Endosc. 2022, 36, 5784–5793. [Google Scholar] [CrossRef] [PubMed]
  43. Weijs, T.J.; Ruurda, J.P.; Nieuwenhuijzen, G.A.; van Hillegersberg, R.; Luyer, M.D. Strategies to reduce pulmonary complications after esophagectomy. World J. Gastroenterol. 2013, 19, 6509–6514. [Google Scholar] [CrossRef] [PubMed]
  44. Oshikiri, T.; Takiguchi, G.; Hasegawa, H.; Yamamoto, M.; Kanaji, S.; Yamashita, K.; Matsuda, T.; Nakamura, T.; Suzuki, S.; Kakeji, Y. Postoperative recurrent laryngeal nerve palsy is associated with pneumonia in minimally invasive esophagectomy for esophageal cancer. Surg. Endosc. 2021, 35, 837–844. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Flow chart of the literature search according to preferred reporting items for systematic reviews and meta-analyses statement.
Figure 1. Flow chart of the literature search according to preferred reporting items for systematic reviews and meta-analyses statement.
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Figure 2. Forest plot of IONM for RLNP. Abbreviations: RLNP—recurrent laryngeal nerve palsy, IONM—intraoperative neuromonitoring.
Figure 2. Forest plot of IONM for RLNP. Abbreviations: RLNP—recurrent laryngeal nerve palsy, IONM—intraoperative neuromonitoring.
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Figure 3. Forest plot of IONM for number of mediastinal LN dissected. Abbreviations: IONM—intraoperative neuromonitoring.
Figure 3. Forest plot of IONM for number of mediastinal LN dissected. Abbreviations: IONM—intraoperative neuromonitoring.
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Figure 4. Forest plot of IONM for aspiration. Abbreviations: IONM—intraoperative neuromonitoring.
Figure 4. Forest plot of IONM for aspiration. Abbreviations: IONM—intraoperative neuromonitoring.
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Figure 5. Forest plot of IONM for pneumonia. Abbreviations: IONM—intraoperative neuromonitoring.
Figure 5. Forest plot of IONM for pneumonia. Abbreviations: IONM—intraoperative neuromonitoring.
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Figure 6. Forest plot of IONM for chylothorax. Abbreviations: IONM—intraoperative neuromonitoring.
Figure 6. Forest plot of IONM for chylothorax. Abbreviations: IONM—intraoperative neuromonitoring.
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Figure 7. Forest plot of IONM for anastomotic leakage. Abbreviations: IONM—intraoperative neuromonitoring.
Figure 7. Forest plot of IONM for anastomotic leakage. Abbreviations: IONM—intraoperative neuromonitoring.
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Figure 8. Forest plot of IONM for total LN dissected. Abbreviations: IONM—intraoperative neuromonitoring.
Figure 8. Forest plot of IONM for total LN dissected. Abbreviations: IONM—intraoperative neuromonitoring.
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Figure 9. Forest plot of IONM for POHS. Abbreviations: IONM—intraoperative neuromonitoring, POHS—postoperative hospital stay.
Figure 9. Forest plot of IONM for POHS. Abbreviations: IONM—intraoperative neuromonitoring, POHS—postoperative hospital stay.
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Figure 10. Forest plot of IONM for total operation time. Abbreviations: IONM—intraoperative neuromonitoring.
Figure 10. Forest plot of IONM for total operation time. Abbreviations: IONM—intraoperative neuromonitoring.
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Table
Table 1. Characteristics of included studies.
Table 1. Characteristics of included studies.
AuthorYear of PublicationStudy PeriodRegionStudy DesignGroupSEX (Male/Female)Age (Mean ± SD)Tumor Location (Upper/Middle/Lower)Pathology (SCC/AC/Other)Neoadjuvant Therapy (NO/CT/CRT)N Stage (N0/N1/N2/N3)Stage (0/I/II/III/IV)
Shuhei Komatsu [20]20222014–2019JapanRCSIONM19/672 (53–81) a3/13/938/3/019/6 b11/6/7/10/8/6/10/1
Control10/662.99 ± 8.815/45/2011/5 b8/4/1/30/8/2/3/3
Chang-Lun Huang [21]20222015–2020ROCRCSIONM34/467 (47–80) a21/38/2533/4/123/15 b19/8/11/0N/A
Control34/367 (53–77) a5/10/2634/2/117/20 b17/13/7/0
LuoZhao [22]20222016–2020ChinaRCSIONM59/1168 (41–84) a8/25/21N/A45/22/3N/A0/25/18/22/5
Control70/1072 (50–85) a3/7/657/21/20/27/16/34/3
Masami Yuda [23]20222011–2018JapanRCSIONM118/2461.96 ± 7.126/49/25133/5/452/86/465/45/21/110/36/55/53/9
Control77/1168 (54–81) a11/20/1639/3/321/24/025/8/7/50/12/15/16/2
Shigeru Takeda [24]20202009–2018JapanRCSIONM40/767.5 (53–80) a6/23/27N/A21/26 bN/A0/17/9/14/7
Control41/665 (49–80) a3/29/2220/27 b1/18/5/14/9
Daisuke Fujimoto [25]20212015–2018JapanRCSIONM13/460.18 ± 8.9927/11 d16/1/07/10 bN/A0/4/4/8/1
Control50/1065.9 ± 8.116/76/5015/1/09/6 b0/5/2/7/1
Hiroyuki Kobayashi [26]20182009–2017JapanRCSIONM25/666.33 a4/8/526/3/217/14/0N/A0/11/10/9/1
Control44/1263 ± 912/18/051/2/330/25/10/28/18/9/1
Zhu Weipeng [27]20182015–2017ChinaRCTIONM26/459.94 ± 8.9660/42/1230/0/0N/AN/AN/A
Control25/556.16 ± 9.7824/13 d30/0/0
Makoto Hikage [28]20172012–2015JapanRCSIONM49/567.6 ± 6.67/25/1346/5/324/19/1121/17/8/80/17/13/22/2
Control41/1369.47 a1/11/348/4/217/6/3128/17/8/10/21/15/17/1
D. Zhong [29]20142008–2009ChinaRCSIONM45/964 ± 812/18/049/2/345/26 c20/13/15/60/10/12/32/0
Control49/1258.93 ± 9.5930/46/1754/3/449/26 c32/8/17/40/18/19/24/0
Abbreviations: N/A—not available; IONM—intraoperative neuromonitoring; RCS—retrospective case–control study; PCS—prospective cohort study; RCT—randomized controlled trial; SD—standard deviation; SCC—squamous cell carcinoma; AC—adenocarcinoma; CT—chemotherapy; CRT—chemoradiotherapy. Note: a: Age in median (range) b: Neoadjuvant therapy status in (NO/CT&CRT) c: Neoadjuvant therapy status in (CT/RT) d: Tumor location in upper and middle/lower.
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MDPI and ACS Style

Chen, B.; Yang, T.; Wang, W.; Tang, W.; Xie, J.; Kang, M. Application of Intraoperative Neuromonitoring (IONM) of the Recurrent Laryngeal Nerve during Esophagectomy: A Systematic Review and Meta-Analysis. J. Clin. Med. 2023, 12, 565. https://doi.org/10.3390/jcm12020565

AMA Style

Chen B, Yang T, Wang W, Tang W, Xie J, Kang M. Application of Intraoperative Neuromonitoring (IONM) of the Recurrent Laryngeal Nerve during Esophagectomy: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2023; 12(2):565. https://doi.org/10.3390/jcm12020565

Chicago/Turabian Style

Chen, Boyang, Tianbao Yang, Wu Wang, Weifeng Tang, Jinbiao Xie, and Mingqiang Kang. 2023. "Application of Intraoperative Neuromonitoring (IONM) of the Recurrent Laryngeal Nerve during Esophagectomy: A Systematic Review and Meta-Analysis" Journal of Clinical Medicine 12, no. 2: 565. https://doi.org/10.3390/jcm12020565

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