Size of recurrent laryngeal nerve as a new risk factor for postoperative vocal cord paralysis

Size of recurrent laryngeal nerve as a new risk factor for postoperative vocal cord paralysis Summary Recurrent laryngeal nerve paralysis (RLNP) is a frequent and serious complication following esophageal cancer surgery. Therefore, this study aims to evaluate the correlation between recurrent laryngeal nerve (RLN) size and RLNP. This was a retrospective study of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2012 to December 2014. Eighty-four patients were included in the primary analysis. Diameter of the RLN was measured using the digital video recording of surgical procedures by the ratio between scissor and RLN. For evaluation of vocal cord paralysis or paresis, indirect laryngoscopy was performed. Because RLNP more frequently occurs on the left side than the right, we evaluated the correlation between size of the left RLN and left RLNP. The median size of the left RLN was 1.51 mm. We found that the incidence of postoperative left RLNP (Clavien–Dindo classification ≥1) was significantly higher (71% vs. 24%; P < 0.001) in thin RLNs (≤1.5 mm) than in thick RLNs (>1.5 mm). Thin RLN (P < 0.001), female sex (P = 0.025), and being overweight (P = 0.034) were identified as significant independent risk factors for postoperative RLNP. RLNP more easily occurred when the RLN was thin. It is difficult to confirm occurrence of postoperative RLNP before and at extubation. Therefore, it is helpful to know its risk factors including size of RLN. INTRODUCTION Esophageal cancer is strongly associated with high mortality and is the sixth most common cause of death by cancer, with a worldwide estimate of 455,800 new cases and 400,200 deaths in 2012.1 Because of the high mortality rate of esophageal cancer, various therapeutic methods have been considered and examined, including extensive lymph node (LN) dissection, termed three-field lymphadenectomy (FL). Two FL of the mediastinal and abdominal regions has been common for esophageal cancer; however, it has been associated with frequent metastasis and recurrence in the cervical LNs and LNs along the recurrent laryngeal nerve (RLN).2,3 Meanwhile, 3-FL has been reported since the early 1980s;4,5 the procedure comprises cervical, mediastinal (including LNs along the bilateral RLNs), and abdominal LN dissection. In 2014, Ma et al. conducted a meta-analysis regarding 3-FL and 2-FL and showed that 3-FL improved overall survival rate, but had more complications, particularly recurrent laryngeal nerve paralysis (RLNP).6 Although 3-FL may reduce the mortality rate, the danger of increased RLNP risk is indispensable for patients and healthcare providers. Patients with RLNP present with voice disturbances and risks for tracheotomy and aspiration pneumonia. RLNP is one of the most frequent and serious complications after esophagectomy, despite best operative management. And there is a difficulty in confirming occurrence of it before and at extubation. However, there were few reports demonstrated the risk factors for RLNP after esophagectomy, and especially there was no report about the risk factors for RLNP after thoracoscopic esophagectomy. Therefore, it is necessary to know its risk factors to clarify the pathophysiology of it and to guide prevention secondary complications. Injury of the RLN is thought due to stretching of the nerve, or transmission of heat from electrocautery.7 We thought that thin nerves may be sensitive to stretching and allow heat transfer into the center of nerve. Therefore, we hypothesized that thin RLN may affect RLNP after esophagectomy with 3-FL. This study aims to evaluate the correlation between RLN size and postoperative RLNP. MATERIALS AND METHODS Study design and study population This was a retrospective study on esophageal cancer patients who underwent thoracoscopic esophagectomy performed by 3 esophageal surgery specialists of the Japan Esophageal Society with lymphadenectomy along the RLN from January 2012 to December 2014 (Fig. 1). The indications for thoracoscopic esophagectomy in our facility were clinically T1–3 tumors located in thoracic esophagus excepting following cases: (1) salvage surgery after definitive chemoradiotherapy and (2) bulky metastatic LNs.8 We reviewed the medical records of these patients after approval by the ethics committee of Keio University School of Medicine (approval number 20,150,044). Patients were excluded if the thoracoscopic surgery was converted to open thoracotomy before exteriorization of the RLN (n = 2) or if they did not undergo lymphadenectomy along the RLN (n = 3). We excluded patients with unavailable digital video recordings of the surgical procedures that were used to measure RLN size (n = 13). We also excluded those who did not undergo direct laryngoscopy for any reason, such as refusal (n = 2). The final study population comprised 84 patients; none of these patients had RLNP before esophagectomy. Fig. 1 View largeDownload slide Flow of patient inclusion in this study from January 2012 to December 2014. RLN, recurrent laryngeal nerve. Fig. 1 View largeDownload slide Flow of patient inclusion in this study from January 2012 to December 2014. RLN, recurrent laryngeal nerve. 3-FL was performed as described previously.9 In brief, the paraesophageal and paratracheal LNs along the bilateral RLNs were dissected through a right transthoracic approach. To prevent thermal damage of electrocautery to RLN, a pair of scissors was used to expose the left RLN between the aortic arch and the thoracic inlet (Fig. 2) and the right RLN from its origin to the level of the right subclavian artery. Through a bilateral cervical incision, supraclavicular LNs and the paraesophageal LNs along the bilateral RLNs were dissected. The celiac and parahiatal LNs in the abdomen were dissected. Fig. 2 View largeDownload slide After lymphadenectomy along the left RLN. Retract the esophagus to the posterior side, the trachea to the anterior. The left RLN was exposed between the aortic arch. RLN, recurrent laryngeal nerve. Fig. 2 View largeDownload slide After lymphadenectomy along the left RLN. Retract the esophagus to the posterior side, the trachea to the anterior. The left RLN was exposed between the aortic arch. RLN, recurrent laryngeal nerve. The diameter of the RLN was measured on the basis of the review of the digital video recordings of the surgical procedures. At that time, we did not collect data of vocal cord assessment yet. The other clinical data of the patients were obtained from their medical records and from the database of esophageal cancer in our hospital. It is considered that there is difference in sizes of bilateral RLN, because length and course of RLN differ between right and left sides. Therefore, we determined to choose one side of RLN for evaluation. In this study, RLNP developed on the left in 34 patients, on the right in 2 patients, and on both sides in 6 patients. Because it is known that RLNP occurs more frequently on the left than the right side after 3-FL,7 we evaluated the correlation between the size of the left RLN and postoperative left RLNP. To understand the differences caused by RLN size, we classified the patients into two groups based on the median size of the left RLN: thin RLN and thick RLN. Through a right transthoracic approach, the right RLN is found and exposed before the left RLN. Therefore, we also evaluated the association of sizes of bilateral RLN to predict size of the left RLN by size of the right RLN. Size measurement of RLN We used single-use scissor tips (Microline Surgical, Inc., Beverly, MA, USA) when we exposed the RLNs. Because RLNs are thin, about 1 to 2 mm in size, measurement of the diameter of the nerves was based on the ratio between the scissors and the RLN. Measurement of the left RLN was taken at the level of the aortic arch (Fig. 3). The tip of the scissors was measured when cutting plane of the scissors came in contact with the RLN in parallel. The still images were captured from the video of the surgical procedures. Using magnified still images, the ratio between the scissors and the RLN was measured by ImageJ, an open source program.10 Measurement of the right RLN was taken at the level of the subclavian artery and performed in the same way to the left side. Fig. 3 View largeDownload slide Measurement of RLN size. The diameter of the nerves was measured by the ratio between the scissors and the RLN. RLN, recurrent laryngeal nerve. Fig. 3 View largeDownload slide Measurement of RLN size. The diameter of the nerves was measured by the ratio between the scissors and the RLN. RLN, recurrent laryngeal nerve. Among the 84 patients, the median size of the left RLN was 1.51 mm. Patients with RLNs ≤1.5 mm (thin RLN, n = 42) were compared with patients with RLNs > 1.5 mm (thick RLN, n = 42). Vocal cord assessment We routinely performed the videoendoscopic swallowing study (VESS) before resumption of diet, usually on the seventh postoperative day, to evaluate for swallowing function. When we perform VESS, we also check vocal cord paralysis (complete loss of nerve input to the voice box muscles) or paresis (partial loss of nerve input to the voice box muscles). In this study, postoperative RLNP was defined as the presence of vocal cord paralysis or paresis. Patients with postoperative RLNP were follow-up for a minimum of one year. If recovery of vocal cord occurred, RLNP was transient; if RLNP did not recover until observation period of at least 1 year or patients received surgical treatment of vocal cord paralysis remaining completely unchanged, RLNP was permanent. Classification of RLNP according to the Clavien–Dindo (CD) system Postoperative RLNP was classified using the CD classification of surgical complications.11 A grade I complication was defined as any deviation from the normal postoperative course without a need for treatment. In this study, laryngoscopy-diagnosed RLNP that did not need any therapy was also classified as grade I. A grade II complication was defined as any abnormality that required pharmacologic treatment or total parenteral nutrition. A grade III complication was defined as any abnormality requiring surgical, endoscopic, or radiological intervention. A grade IV complication was defined as any life-threatening complication requiring intensive care unit management. A grade V complication was defined as death from the complication. Statistical analysis Statistical analyses were conducted using the STATA software 13.0 (Stata Corporation, College Station, TX, USA). Pearson's chi-squared test was used for comparison of categorical variables. Student's t-test and Mann–Whitney U test were used to compare continuous variables. Simple and multiple logistic regression models were used to analyze the correlations. For all procedures, a P value < 0.050 was considered statistically significant. RESULTS Patient characteristics We included a total of 84 patients: 42 in the thick RLN group and 42 in the thin RLN group. Both groups were similar in all baseline characteristics (Table 1). Patients with thin RLN, 31 men and 11 women, had a mean age of 63.1 years and a mean body mass index (BMI) of 22.2. Patients with thick RLN, 35 men and 7 women, had a mean age of 63.5 years and a mean BMI of 22.0. The majority of patients in both groups had squamous cell carcinoma located in the middle thoracic esophagus. Table 1 Baseline characteristics of patients, according to RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 Data are presented a number (%) or mean (SD). BMI, body mass index; SD, standard deviation; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Table 1 Baseline characteristics of patients, according to RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 Data are presented a number (%) or mean (SD). BMI, body mass index; SD, standard deviation; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Table 2 shows the comparison of surgical outcomes between both groups. There were no significant differences between the groups in terms of thoracic operation time, amount of bleeding, presence of metastatic LNs along the left RLN, and number of dissected LNs along the left RLN. There were also no significant differences between the groups in terms of postoperative length of hospital stay and postoperative pneumonia. Grade I RLNP was noted in 55% (n = 23) in the thin RLN group and in 17% (n = 7) in the thick RLN group. Grades II–IV RLNP was noted in 17% (n = 7) in the thin RLN group and in 7% (n = 3) in the thick RLN group. Table 2 Comparison of surgical outcomes based on RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) *P < 0.001. CD, Clavien–Dindo; IQR, interquartile range; LN, lymph node; RLN, recurrent laryngeal nerve; RLNP, recurrent laryngeal nerve paralysis; Prolonged intubation after surgery was defined as >48 h23–28 after induction of general anesthesia. View Large Table 2 Comparison of surgical outcomes based on RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) *P < 0.001. CD, Clavien–Dindo; IQR, interquartile range; LN, lymph node; RLN, recurrent laryngeal nerve; RLNP, recurrent laryngeal nerve paralysis; Prolonged intubation after surgery was defined as >48 h23–28 after induction of general anesthesia. View Large Association between Size of RLN and postoperative RLNP The incidence of ≥grade I postoperative left RLNP was significantly higher in the thin RLN group than in the thick RLN group (71% vs. 24%; P < 0.001) (Table 2). Based on simple logistic regression analysis of RLNP-related factors, which were chosen on the basis of our hypothesis (size of left RLN) and previous literature (BMI,12 operation time,7 age,7,13 gender14), the major risk factors for postoperative RLNP were thin RLN (P < 0.001), female sex (P = 0.023), and overweight status (P = 0.035) (Table 3). Age and operation time were not significant risk factors in this study. Multiple logistic regression analysis showed that thin RLN (P < 0.001), female sex (P = 0.025), and overweight status (P = 0.034) were independently associated with postoperative RLNP. Table 3 Simple and multiple logistic regression analysis of the factors affecting RLNP Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 *P < 0.001; **P < 0.05. BMI, body mass index; CI, confidence interval; OR, odds ratio; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Table 3 Simple and multiple logistic regression analysis of the factors affecting RLNP Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 *P < 0.001; **P < 0.05. BMI, body mass index; CI, confidence interval; OR, odds ratio; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Movement of the paralyzed vocal cords There were 40 patients who developed left RLNP. Vocal cold paresis was shown in 9 patients (23%) and paralysis was observed in 31 patients (78%). Among the 31 cases with vocal cord paralysis, vocal fold position was paramedian in 21 (68%), median in 8 (26%), intermediate in 1 (3%), and in abduction in 1 (3%). The RLN in patients with vocal cord paralysis tended to be thinner than that in patients with paresis, although there was no statistically significant difference (median, 1.41 vs. 1.19 mm; P = 0.097, Fig. 4). Fig. 4 View largeDownload slide Scatter plot of RLN size in patients with normal vocal cord movement, paresis, and paralysis. Normal, patients with normal vocal cord movement after surgery; Paralysis, patients with postoperative vocal cord paralysis; Paresis, patients with postoperative vocal cord paresis; RLN, recurrent laryngeal nerve. Fig. 4 View largeDownload slide Scatter plot of RLN size in patients with normal vocal cord movement, paresis, and paralysis. Normal, patients with normal vocal cord movement after surgery; Paralysis, patients with postoperative vocal cord paralysis; Paresis, patients with postoperative vocal cord paresis; RLN, recurrent laryngeal nerve. A comparison between transient and permanent RLNP is shown in Table 2. Among 84 patients, transient RLNP occurred in 34 (41%) and lasted from 2 weeks to 12 months. Permanent RLNP occurred in 6 patients (7%); four of these patients underwent vocal cord injection or thyroplasty upon their request for voice restoration. All cases with vocal cord paresis after surgery showed transient RLNP. Prediction of size of the left RLN Figure 5 showed the scatter plot between sizes of right and left RLNs. The two variables were significantly correlated with each other (P < 0.001). According to the fitted line, 1.50 mm of the left RLN equated to 1.38 mm of the right RLN that was approximately 1.5 times wider than the tip size of the scissors. Fig. 5 View largeDownload slide The correlation between sizes of right and left RLNs. Horizontal axis of the scatter plot: size of the right RLN; vertical axis: size of the left RLN; the fitted line: a result of a linear regression of the two variables. RLN, recurrent laryngeal nerve. Fig. 5 View largeDownload slide The correlation between sizes of right and left RLNs. Horizontal axis of the scatter plot: size of the right RLN; vertical axis: size of the left RLN; the fitted line: a result of a linear regression of the two variables. RLN, recurrent laryngeal nerve. DISCUSSION In this study, we explored the association between RLN size and postoperative RLNP and found out that RLN size was a new risk factor for RLNP. Most of the previous studies about the risk factors for RLNP were carried out for thyroid surgery.13-15 These studies revealed that the risk factors for RLNP after thyroid surgery were malignancy,13,15,16 repeat surgery,13-16 no nerve identification,13,14,16 advanced age,13 female sex,14 and low- or medium-volume hospital.13,14 There were few reports demonstrated the risk factors for RLNP after esophagectomy. In this study, we identified RLN size, female sex, and overweight status (BMI ≥ 25 kg/m2) as risk factors for RLNP after esophagectomy. Scipione et al.12 studied obese patients (BMI ≥ 35 kg/m2) who underwent esophagectomy for malignant and benign diseases and reported that obese patients had more risk for RLN injury than nonobese patients. The cutoff point and distribution of BMI were different between this study and the study by Scipione et al.; however, a high BMI could affect postoperative RLNP. We chose a BMI of 25 kg/m2 as cutoff point because there was no patient with a BMI of ≥35 kg/m2. In a previous randomized trial that compared cervical anastomosis with thoracic anastomosis, Okuyama et al.17 suggested RLNP occurred more frequently in patients with cervical anastomosis than those with thoracic anastomosis. In contrast, Walther et al.18 reported that there was no statistically significant difference in the occurrence of RLNP between both groups. This study did not analyze anastomotic site because most of our patients underwent cervical anastomosis and only two patients underwent thoracic anastomosis. We found that age and operation time were not significantly associated with postoperative RLNP. Recently, however, Koyanagi et al.7 examined the clinical predictors of RLNP after esophagectomy and reported advanced age (≥64 years old) and operation time as independent risk factors for postoperative RLNP. They also reported that the rate of RLNP tended to be higher in women than in men (37.6% vs. 27.7%). The discrepancy between our outcomes and the previously reported results may be accounted for by differences in patient population and sample number. For example, all patients in this study underwent thoracoscopic esophagectomy, while most of patients in Koyanagi's study underwent transthoracic esophagectomy. In this study, we found the thin RLN affected postoperative RLNP. The mechanism of postoperative RLNP is thought due to stretching of the nerve, or transmission of heat from electrocautery.7 The mechanism could explain the reasons why RLNP becomes common in the thin RLN. In surgical procedure, sometimes we need stretching RLN to separate LN along the RLN. Thin nerves may be sensitive to stretching, then thin RLN affects postoperative RLNP. To prevent thermal damage of electrocautery to RLN, a pair of scissors was used to expose the RLN in our facility. However, in the facilities where surgical energy devices are used around RLN, the thin RLN can allow heat transfer into the center of nerve, and then RLNP may occur. Voice disorders caused by vocal cord paralysis affect quality of life and job performance.13,19,20 In this study, all cases with vocal cord paresis were transient and recovered to the previous voice quality, whereas several cases with vocal cord paralysis were permanent and needed additional treatment to resolve voice disturbances. Similar to previous literature,14-16,21 majority of postoperative RLNP cases in this study were transient. Transient RLNP usually lasts from a few days to 1 year;16,21 therefore, a diagnosis of permanent RLNP may be thought of as a clinically significant problem. Regardless, it is important to note that RLNP, whether transient or permanent, should be diagnosed before starting diet because RLNP after esophagectomy was reported to be associated with pneumonia22 and respiratory complications.7 In this study, size of the left RLN was correlated with size of the right RLN. Therefore, we can expect size of the left RLN when the right RLN is identified. The ratio to the tip of the scissors may be useful to calculate intraoperatively whether the right RLN is thin or thick. If the right RLN is thin, we should consider the left RLN may be thin. And we should also identify the left RLN and dissect LNs along the RLN with particular attention, although it is needless to say that careful operative technique should always be required for all patients. In conclusion, RLN size was suggested as a new risk factor for RLNP. Because it is difficult to confirm occurrence of postoperative RLNP before and at extubation, it is helpful to know its risk factors including RLN size. RLNP occurs more frequently on the left than the right side after 3-FL. If the right RLN is thin, we should consider the left RLN to be thin and identify the left RLN carefully. Because postoperative RLNP is an undesirable complication that should be reduced to a minimum, future prospective trials are needed to validate our findings. Notes Specific author contributions: Study conception and design: Yoshiyuki Saito, Hiroya Takeuchi,Koichi Suda,, Hirofumi Kawakubo; Analysis and interpretation of data: Yoshiyuki Saito, Hiroya Takeuchi, Koichi Suda, Hirofumi Kawakubo; Drafting manuscript: Yoshiyuki Saito, Hiroya Takeuchi; Revising the manuscript: Kazumasa Fukuda, Rieko Nakamura, Norihito Wada,Yuko Kitagawa; Final approval of the article: Yuko Kitagawa. Disclosures: The authors have no conflicts of interest to disclose. References 1 Torre L A , Bray F , Siegel R L , Ferlay J , Lortet-Tieulent J , Jemal A . Global cancer statistics, 2012 . CA Cancer J Clin 2015 ; 65 : 87 – 108 . Google Scholar CrossRef Search ADS PubMed 2 Sannohe Y , Hiratsuka R , Doki K . Lymph node metastases in cancer of the thoracic esophagus . Am J Surg 1981 ; 141 : 216 – 8 . Google Scholar CrossRef Search ADS PubMed 3 Isono K , Onoda S , Okuyama K , Sato H . Recurrence of intrathoracic esophageal cancer . Jpn J Clin Oncol 1985 ; 15 : 49 – 60 . Google Scholar PubMed 4 Isono K , Sato H , Nakayama K . Results of a nationwide study on the three-field lymph node dissection of esophageal cancer . Oncology 1991 ; 48 : 411 – 20 . Google Scholar CrossRef Search ADS PubMed 5 Altorki N , Kent M , Ferrara C , Port J . Three-field lymph node dissection for squamous cell and adenocarcinoma of the esophagus . Ann Surg 2002 ; 236 : 177 – 83 . Google Scholar CrossRef Search ADS PubMed 6 Ma G W , Situ D R , Ma Q L et al. Three-field vs two-field lymph node dissection for esophageal cancer: a meta-analysis . World J Surg 2014 ; 20 : 18022 – 30 . 7 Koyanagi K , Igaki H , Iwabu J , Ochiai H , Tachimori Y . Recurrent laryngeal nerve paralysis after esophagectomy: respiratory complications and role of nerve reconstruction . Tohoku J Exp Med 2015 ; 237 : 1 – 8 . Google Scholar CrossRef Search ADS PubMed 8 Kaburagi T , Takeuchi H , Kawakubo H , Omori T , Ozawa S , Kitagawa Y . Clinical utility of a novel hybrid position combining the left lateral decubitus and prone positions during thoracoscopic esophagectomy . World J Surg 2014 ; 38 : 410 – 8 . Google Scholar CrossRef Search ADS PubMed 9 Kawakubo H , Takeuchi H , Kitagawa Y . Current status and future perspectives on minimally invasive esophagectomy . Korean J Thorac Cardiovasc Surg 2013 ; 46 : 241 – 8 . Google Scholar CrossRef Search ADS PubMed 10 Schneider C A , Rasband W S , Eliceiri K W . NIH Image to ImageJ: 25 years of image analysis . Nat Methods 2012 ; 9 : 671 – 5 . Google Scholar CrossRef Search ADS PubMed 11 Dindo D , Demartines N , Clavien P A . Classification of surgical complications . Ann Surg 2004 ; 240 : 205 – 13 . Google Scholar CrossRef Search ADS PubMed 12 Scipione C N , Chang A C , Pickens A , Lau C L , Orringer M B . Transhiatal esophagectomy in the profoundly obese: implications and experience . Ann Thorac Surg 2007 ; 84 : 376 – 83 ; discussion 83 . Google Scholar CrossRef Search ADS PubMed 13 Dralle H , Sekulla C , Haerting J et al. Risk factors of paralysis and functional outcome after recurrent laryngeal nerve monitoring in thyroid surgery . Surgery 2004 ; 136 : 1310 – 22 . Google Scholar CrossRef Search ADS PubMed 14 Thomusch O , Machens A , Sekulla C et al. Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany . World J Surg 2000 ; 24 : 1335 – 41 . 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Ann Surg 2003 ; 238 : 803 – 14 ; discussion 12–4 . Google Scholar CrossRef Search ADS PubMed 19 Smith E , Taylor M , Mendoza M , Barkmeier J , Lemke J , Hoffman H . Spasmodic dysphonia and vocal fold paralysis: outcomes of voice problems on work-related functioning . J Voice 1998 ; 12 : 223 – 32 . Google Scholar CrossRef Search ADS PubMed 20 Smith E , Verdolini K , Gray S et al. Effect of voice disorders on quality of life . J Med Speech Lang Pathol. 1996 ; 4 : 223 – 44 . 21 Harness J K , Fung L , Thompson N W , Burney R E , McLeod M K . Total thyroidectomy: complications and technique . World J Surg 1986 ; 10 : 781 – 5 . Google Scholar CrossRef Search ADS PubMed 22 Gockel I , Kneist W , Keilmann A , Junginger T . Recurrent laryngeal nerve paralysis (RLNP) following esophagectomy for carcinoma . Eur J Surg Oncol 2005 ; 31 : 277 – 81 . Google Scholar CrossRef Search ADS PubMed 23 Moraes D P , Sassi F C , Mangilli L D , Zilberstein B , de Andrade C R . 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J Head Trauma Rehabil 1999 ; 14 : 454 – 61 . Google Scholar CrossRef Search ADS PubMed 28 de Larminat V , Montravers P , Dureuil B , Desmonts J M . Alteration in swallowing reflex after extubation in intensive care unit patients . Crit Care Med 1995 ; 23 : 486 – 90 . Google Scholar CrossRef Search ADS PubMed © The Authors 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diseases of the Esophagus Oxford University Press

Size of recurrent laryngeal nerve as a new risk factor for postoperative vocal cord paralysis

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The International Society for Diseases of the Esophagus
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© The Authors 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.
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1120-8694
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1442-2050
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10.1093/dote/dox162
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Abstract

Summary Recurrent laryngeal nerve paralysis (RLNP) is a frequent and serious complication following esophageal cancer surgery. Therefore, this study aims to evaluate the correlation between recurrent laryngeal nerve (RLN) size and RLNP. This was a retrospective study of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2012 to December 2014. Eighty-four patients were included in the primary analysis. Diameter of the RLN was measured using the digital video recording of surgical procedures by the ratio between scissor and RLN. For evaluation of vocal cord paralysis or paresis, indirect laryngoscopy was performed. Because RLNP more frequently occurs on the left side than the right, we evaluated the correlation between size of the left RLN and left RLNP. The median size of the left RLN was 1.51 mm. We found that the incidence of postoperative left RLNP (Clavien–Dindo classification ≥1) was significantly higher (71% vs. 24%; P < 0.001) in thin RLNs (≤1.5 mm) than in thick RLNs (>1.5 mm). Thin RLN (P < 0.001), female sex (P = 0.025), and being overweight (P = 0.034) were identified as significant independent risk factors for postoperative RLNP. RLNP more easily occurred when the RLN was thin. It is difficult to confirm occurrence of postoperative RLNP before and at extubation. Therefore, it is helpful to know its risk factors including size of RLN. INTRODUCTION Esophageal cancer is strongly associated with high mortality and is the sixth most common cause of death by cancer, with a worldwide estimate of 455,800 new cases and 400,200 deaths in 2012.1 Because of the high mortality rate of esophageal cancer, various therapeutic methods have been considered and examined, including extensive lymph node (LN) dissection, termed three-field lymphadenectomy (FL). Two FL of the mediastinal and abdominal regions has been common for esophageal cancer; however, it has been associated with frequent metastasis and recurrence in the cervical LNs and LNs along the recurrent laryngeal nerve (RLN).2,3 Meanwhile, 3-FL has been reported since the early 1980s;4,5 the procedure comprises cervical, mediastinal (including LNs along the bilateral RLNs), and abdominal LN dissection. In 2014, Ma et al. conducted a meta-analysis regarding 3-FL and 2-FL and showed that 3-FL improved overall survival rate, but had more complications, particularly recurrent laryngeal nerve paralysis (RLNP).6 Although 3-FL may reduce the mortality rate, the danger of increased RLNP risk is indispensable for patients and healthcare providers. Patients with RLNP present with voice disturbances and risks for tracheotomy and aspiration pneumonia. RLNP is one of the most frequent and serious complications after esophagectomy, despite best operative management. And there is a difficulty in confirming occurrence of it before and at extubation. However, there were few reports demonstrated the risk factors for RLNP after esophagectomy, and especially there was no report about the risk factors for RLNP after thoracoscopic esophagectomy. Therefore, it is necessary to know its risk factors to clarify the pathophysiology of it and to guide prevention secondary complications. Injury of the RLN is thought due to stretching of the nerve, or transmission of heat from electrocautery.7 We thought that thin nerves may be sensitive to stretching and allow heat transfer into the center of nerve. Therefore, we hypothesized that thin RLN may affect RLNP after esophagectomy with 3-FL. This study aims to evaluate the correlation between RLN size and postoperative RLNP. MATERIALS AND METHODS Study design and study population This was a retrospective study on esophageal cancer patients who underwent thoracoscopic esophagectomy performed by 3 esophageal surgery specialists of the Japan Esophageal Society with lymphadenectomy along the RLN from January 2012 to December 2014 (Fig. 1). The indications for thoracoscopic esophagectomy in our facility were clinically T1–3 tumors located in thoracic esophagus excepting following cases: (1) salvage surgery after definitive chemoradiotherapy and (2) bulky metastatic LNs.8 We reviewed the medical records of these patients after approval by the ethics committee of Keio University School of Medicine (approval number 20,150,044). Patients were excluded if the thoracoscopic surgery was converted to open thoracotomy before exteriorization of the RLN (n = 2) or if they did not undergo lymphadenectomy along the RLN (n = 3). We excluded patients with unavailable digital video recordings of the surgical procedures that were used to measure RLN size (n = 13). We also excluded those who did not undergo direct laryngoscopy for any reason, such as refusal (n = 2). The final study population comprised 84 patients; none of these patients had RLNP before esophagectomy. Fig. 1 View largeDownload slide Flow of patient inclusion in this study from January 2012 to December 2014. RLN, recurrent laryngeal nerve. Fig. 1 View largeDownload slide Flow of patient inclusion in this study from January 2012 to December 2014. RLN, recurrent laryngeal nerve. 3-FL was performed as described previously.9 In brief, the paraesophageal and paratracheal LNs along the bilateral RLNs were dissected through a right transthoracic approach. To prevent thermal damage of electrocautery to RLN, a pair of scissors was used to expose the left RLN between the aortic arch and the thoracic inlet (Fig. 2) and the right RLN from its origin to the level of the right subclavian artery. Through a bilateral cervical incision, supraclavicular LNs and the paraesophageal LNs along the bilateral RLNs were dissected. The celiac and parahiatal LNs in the abdomen were dissected. Fig. 2 View largeDownload slide After lymphadenectomy along the left RLN. Retract the esophagus to the posterior side, the trachea to the anterior. The left RLN was exposed between the aortic arch. RLN, recurrent laryngeal nerve. Fig. 2 View largeDownload slide After lymphadenectomy along the left RLN. Retract the esophagus to the posterior side, the trachea to the anterior. The left RLN was exposed between the aortic arch. RLN, recurrent laryngeal nerve. The diameter of the RLN was measured on the basis of the review of the digital video recordings of the surgical procedures. At that time, we did not collect data of vocal cord assessment yet. The other clinical data of the patients were obtained from their medical records and from the database of esophageal cancer in our hospital. It is considered that there is difference in sizes of bilateral RLN, because length and course of RLN differ between right and left sides. Therefore, we determined to choose one side of RLN for evaluation. In this study, RLNP developed on the left in 34 patients, on the right in 2 patients, and on both sides in 6 patients. Because it is known that RLNP occurs more frequently on the left than the right side after 3-FL,7 we evaluated the correlation between the size of the left RLN and postoperative left RLNP. To understand the differences caused by RLN size, we classified the patients into two groups based on the median size of the left RLN: thin RLN and thick RLN. Through a right transthoracic approach, the right RLN is found and exposed before the left RLN. Therefore, we also evaluated the association of sizes of bilateral RLN to predict size of the left RLN by size of the right RLN. Size measurement of RLN We used single-use scissor tips (Microline Surgical, Inc., Beverly, MA, USA) when we exposed the RLNs. Because RLNs are thin, about 1 to 2 mm in size, measurement of the diameter of the nerves was based on the ratio between the scissors and the RLN. Measurement of the left RLN was taken at the level of the aortic arch (Fig. 3). The tip of the scissors was measured when cutting plane of the scissors came in contact with the RLN in parallel. The still images were captured from the video of the surgical procedures. Using magnified still images, the ratio between the scissors and the RLN was measured by ImageJ, an open source program.10 Measurement of the right RLN was taken at the level of the subclavian artery and performed in the same way to the left side. Fig. 3 View largeDownload slide Measurement of RLN size. The diameter of the nerves was measured by the ratio between the scissors and the RLN. RLN, recurrent laryngeal nerve. Fig. 3 View largeDownload slide Measurement of RLN size. The diameter of the nerves was measured by the ratio between the scissors and the RLN. RLN, recurrent laryngeal nerve. Among the 84 patients, the median size of the left RLN was 1.51 mm. Patients with RLNs ≤1.5 mm (thin RLN, n = 42) were compared with patients with RLNs > 1.5 mm (thick RLN, n = 42). Vocal cord assessment We routinely performed the videoendoscopic swallowing study (VESS) before resumption of diet, usually on the seventh postoperative day, to evaluate for swallowing function. When we perform VESS, we also check vocal cord paralysis (complete loss of nerve input to the voice box muscles) or paresis (partial loss of nerve input to the voice box muscles). In this study, postoperative RLNP was defined as the presence of vocal cord paralysis or paresis. Patients with postoperative RLNP were follow-up for a minimum of one year. If recovery of vocal cord occurred, RLNP was transient; if RLNP did not recover until observation period of at least 1 year or patients received surgical treatment of vocal cord paralysis remaining completely unchanged, RLNP was permanent. Classification of RLNP according to the Clavien–Dindo (CD) system Postoperative RLNP was classified using the CD classification of surgical complications.11 A grade I complication was defined as any deviation from the normal postoperative course without a need for treatment. In this study, laryngoscopy-diagnosed RLNP that did not need any therapy was also classified as grade I. A grade II complication was defined as any abnormality that required pharmacologic treatment or total parenteral nutrition. A grade III complication was defined as any abnormality requiring surgical, endoscopic, or radiological intervention. A grade IV complication was defined as any life-threatening complication requiring intensive care unit management. A grade V complication was defined as death from the complication. Statistical analysis Statistical analyses were conducted using the STATA software 13.0 (Stata Corporation, College Station, TX, USA). Pearson's chi-squared test was used for comparison of categorical variables. Student's t-test and Mann–Whitney U test were used to compare continuous variables. Simple and multiple logistic regression models were used to analyze the correlations. For all procedures, a P value < 0.050 was considered statistically significant. RESULTS Patient characteristics We included a total of 84 patients: 42 in the thick RLN group and 42 in the thin RLN group. Both groups were similar in all baseline characteristics (Table 1). Patients with thin RLN, 31 men and 11 women, had a mean age of 63.1 years and a mean body mass index (BMI) of 22.2. Patients with thick RLN, 35 men and 7 women, had a mean age of 63.5 years and a mean BMI of 22.0. The majority of patients in both groups had squamous cell carcinoma located in the middle thoracic esophagus. Table 1 Baseline characteristics of patients, according to RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 Data are presented a number (%) or mean (SD). BMI, body mass index; SD, standard deviation; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Table 1 Baseline characteristics of patients, according to RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Age (years), mean ± SD 63.3 ± 9.2 63.1 ± 9.6 63.5 ± 8.8 0.83 Gender 0.29  Male 66 (79) 31 (74) 35 (83)  Female 18 (21) 11 (26) 7 (17) BMI (kg/m2), mean ± SD 22.1 ± 3.4 22.2 ± 3.9 22.0 ± 2.8 0.79 WHO performance status 0.17  0 79 (94) 38 (90) 41 (98)  1 5 (6) 4 (10) 1 (3) Histologic type 0.51  Squamous cell carcinoma 77 (92) 39 (93) 38 (90)  Adenocarcinoma 3 (4) 2 (5) 1 (2)  Others 4 (5) 1 (2) 3 (7) Tumor location in the esophagus 0.62  Cervical and upper thoracic 10 (12) 5 (12) 5 (12)  Middle thoracic 48 (57) 26 (62) 22 (52)  Lower thoracic and abdominal 26 (31) 11 (26) 15 (36) Pathologic stage 0.97  Stage 0 or I 37 (44) 19 (45) 18 (43)  Stage IIA or IIB 18 (21) 9 (21) 9 (21)  Stage III or IV 29 (35) 14 (33) 15 (36) Neoadjuvant chemotherapy alone 42 (50) 21 (50) 21 (50) 1.00 Neoadjuvant chemoradiation therapy 4 (5) 3 (7) 1 (2) 0.31 Data are presented a number (%) or mean (SD). BMI, body mass index; SD, standard deviation; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Table 2 shows the comparison of surgical outcomes between both groups. There were no significant differences between the groups in terms of thoracic operation time, amount of bleeding, presence of metastatic LNs along the left RLN, and number of dissected LNs along the left RLN. There were also no significant differences between the groups in terms of postoperative length of hospital stay and postoperative pneumonia. Grade I RLNP was noted in 55% (n = 23) in the thin RLN group and in 17% (n = 7) in the thick RLN group. Grades II–IV RLNP was noted in 17% (n = 7) in the thin RLN group and in 7% (n = 3) in the thick RLN group. Table 2 Comparison of surgical outcomes based on RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) *P < 0.001. CD, Clavien–Dindo; IQR, interquartile range; LN, lymph node; RLN, recurrent laryngeal nerve; RLNP, recurrent laryngeal nerve paralysis; Prolonged intubation after surgery was defined as >48 h23–28 after induction of general anesthesia. View Large Table 2 Comparison of surgical outcomes based on RLN size No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) No. (%) Total n = 84 Thin RLN ≤ 1.5 mm n = 42 Thick RLN > 1.5 mm n = 42 P value Thoracic operation time (min), median (IQR) 279 (257, 310) 274 (259, 294) 286 (255, 314) 0.40 Operative blood loss (mL), median (IQR) 200 (100, 345) 230 (134, 400) 150 (100, 285) 0.10 Number of dissected LNs along the left RLN, median (IQR) 3.0 (2.5, 7.0) 4.0 (2.0, 6.0) 3.0 (2.0, 5.3) 0.52 Presence of metastatic LNs along the left RLN 12 (14) 5 (12) 7 (17) 0.53 Prolonged intubation after surgery 13 (15) 7 (17) 6 (14) 0.76 Postoperative length of hospital stay (day), median (IQR) 27 (20, 38) 29 (23, 37) 22 (19, 47) 0.34 Pneumonia (CD classification ≥Grade II) 19 (23) 12 (29) 7 (17) 0.19 Left RLNP (CD classification ≥Grade I) 40 (48) 30 (71) 10 (24) <0.001*  Grade I/II/III/IV 30/2/6/2 23/2/4/1 7/0/2/1 <0.001* (36/2/7/2) (55/5/10/2) (17/0/5/2) Recovery of left RLNP <0.001*  Transient left RLNP 34 (41) 26 (62) 8 (19)  Permanent left RLNP 6 (7) 4 (10) 2 (5) *P < 0.001. CD, Clavien–Dindo; IQR, interquartile range; LN, lymph node; RLN, recurrent laryngeal nerve; RLNP, recurrent laryngeal nerve paralysis; Prolonged intubation after surgery was defined as >48 h23–28 after induction of general anesthesia. View Large Association between Size of RLN and postoperative RLNP The incidence of ≥grade I postoperative left RLNP was significantly higher in the thin RLN group than in the thick RLN group (71% vs. 24%; P < 0.001) (Table 2). Based on simple logistic regression analysis of RLNP-related factors, which were chosen on the basis of our hypothesis (size of left RLN) and previous literature (BMI,12 operation time,7 age,7,13 gender14), the major risk factors for postoperative RLNP were thin RLN (P < 0.001), female sex (P = 0.023), and overweight status (P = 0.035) (Table 3). Age and operation time were not significant risk factors in this study. Multiple logistic regression analysis showed that thin RLN (P < 0.001), female sex (P = 0.025), and overweight status (P = 0.034) were independently associated with postoperative RLNP. Table 3 Simple and multiple logistic regression analysis of the factors affecting RLNP Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 *P < 0.001; **P < 0.05. BMI, body mass index; CI, confidence interval; OR, odds ratio; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Table 3 Simple and multiple logistic regression analysis of the factors affecting RLNP Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 Simple logistic regression Multiple logistic regression OR (95% CI) P value OR (95% CI) P value Size of left RLN  Thick RLN (>1.5 mm) 1 1  Thin RLN (≤1.5 mm) 7.99 (3.01–21.23) <0.001* 7.64 (2.68–21.82) <0.001* Age (years)  <65 1  ≥65 0.99 (0.42–2.34) 0.983 Female 3.76 (1.20–11.77) 0.023** 5.16 (1.36–19.59) 0.016** BMI (kg/m2)  Normal or underweight (<25) 1 1  Overweight (≥25) 3.79 (1.10–13.11) 0.035** 4.76 (1.13–20.08) 0.034** WHO performance status 1.70 (0.27–10.75) 0.571 Tumor location in the esophagus  Cervical and upper thoracic 1  Middle thoracic 0.61 (0.15–2.45) 0.489  Lower thoracic and abdominal 0.49 (0.11–2.16) 0.345 Pathologic stage  Stage 0 or I 1  Stage IIA or IIB 0.76 (0.24–2.35) 0.631  Stage III or IV 0.77 (0.29–2.04) 0.599 Neoadjuvant therapy 1.5 (0.63–3.56) 0.359 Thoracic operation time (min) 1.00 (0.99–1.01) 0.387 Total operation time (min) 1.00 (0.99–1.00) 0.275 Operative blood loss (ml) 1.00 (1.00–1.00) 0.411 Number of dissected LNs along the left RLN 1.05 (0.93–1.18) 0.467 Presence of Metastatic LNs along the left RLN 0.50 (0.14–1.81) 0.291 Prolonged intubation after surgery 2.90 (0.82–10.31) 0.099 *P < 0.001; **P < 0.05. BMI, body mass index; CI, confidence interval; OR, odds ratio; RLN, recurrent laryngeal nerve; WHO, World Health Organization. View Large Movement of the paralyzed vocal cords There were 40 patients who developed left RLNP. Vocal cold paresis was shown in 9 patients (23%) and paralysis was observed in 31 patients (78%). Among the 31 cases with vocal cord paralysis, vocal fold position was paramedian in 21 (68%), median in 8 (26%), intermediate in 1 (3%), and in abduction in 1 (3%). The RLN in patients with vocal cord paralysis tended to be thinner than that in patients with paresis, although there was no statistically significant difference (median, 1.41 vs. 1.19 mm; P = 0.097, Fig. 4). Fig. 4 View largeDownload slide Scatter plot of RLN size in patients with normal vocal cord movement, paresis, and paralysis. Normal, patients with normal vocal cord movement after surgery; Paralysis, patients with postoperative vocal cord paralysis; Paresis, patients with postoperative vocal cord paresis; RLN, recurrent laryngeal nerve. Fig. 4 View largeDownload slide Scatter plot of RLN size in patients with normal vocal cord movement, paresis, and paralysis. Normal, patients with normal vocal cord movement after surgery; Paralysis, patients with postoperative vocal cord paralysis; Paresis, patients with postoperative vocal cord paresis; RLN, recurrent laryngeal nerve. A comparison between transient and permanent RLNP is shown in Table 2. Among 84 patients, transient RLNP occurred in 34 (41%) and lasted from 2 weeks to 12 months. Permanent RLNP occurred in 6 patients (7%); four of these patients underwent vocal cord injection or thyroplasty upon their request for voice restoration. All cases with vocal cord paresis after surgery showed transient RLNP. Prediction of size of the left RLN Figure 5 showed the scatter plot between sizes of right and left RLNs. The two variables were significantly correlated with each other (P < 0.001). According to the fitted line, 1.50 mm of the left RLN equated to 1.38 mm of the right RLN that was approximately 1.5 times wider than the tip size of the scissors. Fig. 5 View largeDownload slide The correlation between sizes of right and left RLNs. Horizontal axis of the scatter plot: size of the right RLN; vertical axis: size of the left RLN; the fitted line: a result of a linear regression of the two variables. RLN, recurrent laryngeal nerve. Fig. 5 View largeDownload slide The correlation between sizes of right and left RLNs. Horizontal axis of the scatter plot: size of the right RLN; vertical axis: size of the left RLN; the fitted line: a result of a linear regression of the two variables. RLN, recurrent laryngeal nerve. DISCUSSION In this study, we explored the association between RLN size and postoperative RLNP and found out that RLN size was a new risk factor for RLNP. Most of the previous studies about the risk factors for RLNP were carried out for thyroid surgery.13-15 These studies revealed that the risk factors for RLNP after thyroid surgery were malignancy,13,15,16 repeat surgery,13-16 no nerve identification,13,14,16 advanced age,13 female sex,14 and low- or medium-volume hospital.13,14 There were few reports demonstrated the risk factors for RLNP after esophagectomy. In this study, we identified RLN size, female sex, and overweight status (BMI ≥ 25 kg/m2) as risk factors for RLNP after esophagectomy. Scipione et al.12 studied obese patients (BMI ≥ 35 kg/m2) who underwent esophagectomy for malignant and benign diseases and reported that obese patients had more risk for RLN injury than nonobese patients. The cutoff point and distribution of BMI were different between this study and the study by Scipione et al.; however, a high BMI could affect postoperative RLNP. We chose a BMI of 25 kg/m2 as cutoff point because there was no patient with a BMI of ≥35 kg/m2. In a previous randomized trial that compared cervical anastomosis with thoracic anastomosis, Okuyama et al.17 suggested RLNP occurred more frequently in patients with cervical anastomosis than those with thoracic anastomosis. In contrast, Walther et al.18 reported that there was no statistically significant difference in the occurrence of RLNP between both groups. This study did not analyze anastomotic site because most of our patients underwent cervical anastomosis and only two patients underwent thoracic anastomosis. We found that age and operation time were not significantly associated with postoperative RLNP. Recently, however, Koyanagi et al.7 examined the clinical predictors of RLNP after esophagectomy and reported advanced age (≥64 years old) and operation time as independent risk factors for postoperative RLNP. They also reported that the rate of RLNP tended to be higher in women than in men (37.6% vs. 27.7%). The discrepancy between our outcomes and the previously reported results may be accounted for by differences in patient population and sample number. For example, all patients in this study underwent thoracoscopic esophagectomy, while most of patients in Koyanagi's study underwent transthoracic esophagectomy. In this study, we found the thin RLN affected postoperative RLNP. The mechanism of postoperative RLNP is thought due to stretching of the nerve, or transmission of heat from electrocautery.7 The mechanism could explain the reasons why RLNP becomes common in the thin RLN. In surgical procedure, sometimes we need stretching RLN to separate LN along the RLN. Thin nerves may be sensitive to stretching, then thin RLN affects postoperative RLNP. To prevent thermal damage of electrocautery to RLN, a pair of scissors was used to expose the RLN in our facility. However, in the facilities where surgical energy devices are used around RLN, the thin RLN can allow heat transfer into the center of nerve, and then RLNP may occur. Voice disorders caused by vocal cord paralysis affect quality of life and job performance.13,19,20 In this study, all cases with vocal cord paresis were transient and recovered to the previous voice quality, whereas several cases with vocal cord paralysis were permanent and needed additional treatment to resolve voice disturbances. Similar to previous literature,14-16,21 majority of postoperative RLNP cases in this study were transient. Transient RLNP usually lasts from a few days to 1 year;16,21 therefore, a diagnosis of permanent RLNP may be thought of as a clinically significant problem. Regardless, it is important to note that RLNP, whether transient or permanent, should be diagnosed before starting diet because RLNP after esophagectomy was reported to be associated with pneumonia22 and respiratory complications.7 In this study, size of the left RLN was correlated with size of the right RLN. Therefore, we can expect size of the left RLN when the right RLN is identified. The ratio to the tip of the scissors may be useful to calculate intraoperatively whether the right RLN is thin or thick. If the right RLN is thin, we should consider the left RLN may be thin. And we should also identify the left RLN and dissect LNs along the RLN with particular attention, although it is needless to say that careful operative technique should always be required for all patients. In conclusion, RLN size was suggested as a new risk factor for RLNP. Because it is difficult to confirm occurrence of postoperative RLNP before and at extubation, it is helpful to know its risk factors including RLN size. RLNP occurs more frequently on the left than the right side after 3-FL. If the right RLN is thin, we should consider the left RLN to be thin and identify the left RLN carefully. Because postoperative RLNP is an undesirable complication that should be reduced to a minimum, future prospective trials are needed to validate our findings. Notes Specific author contributions: Study conception and design: Yoshiyuki Saito, Hiroya Takeuchi,Koichi Suda,, Hirofumi Kawakubo; Analysis and interpretation of data: Yoshiyuki Saito, Hiroya Takeuchi, Koichi Suda, Hirofumi Kawakubo; Drafting manuscript: Yoshiyuki Saito, Hiroya Takeuchi; Revising the manuscript: Kazumasa Fukuda, Rieko Nakamura, Norihito Wada,Yuko Kitagawa; Final approval of the article: Yuko Kitagawa. Disclosures: The authors have no conflicts of interest to disclose. 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Diseases of the EsophagusOxford University Press

Published: Apr 26, 2018

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