The predictive value of new-onset atrial fibrillation on postoperative morbidity after esophagectomy

The predictive value of new-onset atrial fibrillation on postoperative morbidity after esophagectomy SUMMARY New-onset atrial fibrillation (AF) is frequently observed following esophagectomy and may predict other complications. The aim of the current study was to determine the association between, and the possible predictive value of, new-onset AF and infectious complications following esophagectomy. Consecutive patients who underwent elective esophagectomy with curative intent for esophageal cancer between 2004 and 2016 in the University Medical Center Utrecht were included from a prospective database. The date of diagnosis of the complications included in the current analysis was retrospectively collected from the computerized medical record. The association between new-onset AF and infectious complications was studied in univariable and multivariable logistic regression analyses. A total of 455 patients were included. In 93 (20.4%) patients new-onset AF was encountered after esophagectomy. There were no significant differences in patient and treatment-related characteristics between the patients with and without AF. In 9 (9.7%) patients, AF was the only adverse event following surgery. In multivariable analyses, AF was significantly associated with infectious complications in general (OR 3.00, 95% CI: 1.73–5.21). More specifically, AF was associated with pulmonary complications (OR 2.06, 95% CI: 1.29–3.30), pneumonia (OR 2.41, 95% CI: 1.48–3.91) and anastomotic leakage (OR 3.00, 95% CI: 1.80–4.99). In patients who underwent esophagectomy, new-onset AF was highly associated with infectious complications. AF may serve as an early clinical warning sign for anastomotic leakage. Therefore, further evaluation of patients who develop new-onset AF after esophagectomy is warranted. INTRODUCTION Curative treatment for patients with resectable locally advanced esophageal cancer consists of neoadjuvant chemoradiotherapy followed by esophagectomy with en-bloc lymphadenectomy.1,2 Although mortality following esophagectomy steadily decreased over the past years, morbidity rates remain high compared to other elective cancer surgery.1,3,4 The most frequently encountered postoperative complications include pulmonary complications (12–46%), anastomotic leakage (0–35%), and atrial fibrillation (AF) (12–37%).1,5–10 AF increases the risk of embolic events and hemodynamic instability, potentially resulting in organ hypoperfusion.11 Although the exact pathophysiology of new-onset AF after esophagectomy remains unclear, several retrospective studies demonstrated a significant association between new-onset AF and other postoperative complications.6,8,10 Therefore, it was hypothesized that AF could be of clinical predictive value if AF was shown to precede other postoperative complications. Although the most recent and largest study published to date confirms the association between new-onset AF after esophagectomy and pulmonary complications, it did not demonstrate a significant relation between AF and anastomotic leakage.11 The aim of this study is to determine the association between, and the possible predictive value of, new-onset AF and infectious complications following esophagectomy, with a focus on the 2 most frequently encountered complications after esophagectomy, namely pulmonary complications and anastomotic leakage. METHODS Patients Consecutive patients who underwent an elective esophagectomy for esophageal or gastroesophageal junction cancer with curative intent between 2004 and 2016 at the University Medical Center (UMC) Utrecht were included in this study. Exclusion criteria included preoperative presence of AF and American Association of Anaesthesiologists (ASA) IV classification. Patients included in this study were not given routine AF prophylaxis postoperatively. Patient and treatment-related characteristics as well as surgical outcome data were prospectively recorded in an Institutional Review Board (IRB) approved database. The date of diagnosis of the complications included in the current analysis was retrospectively collected from the computerized medical record. C-reactive protein (CRP) levels were registered at the day of AF diagnosis. This study was approved by the Medical Ethics Review Committee of the UMC Utrecht (IRB-number 13–061/C), and informed consent was waived. Surgical approach The standard surgical approach for esophageal cancer at the UMC Utrecht was a transthoracic robot-assisted minimally invasive esophagectomy. However, some patients underwent an open transthoracic esophagectomy, since they were included in the ROBOT trial.12 When a patient was considered to be too frail to be eligible for a transthoracic approach, a (minimally invasive) transhiatal esophagectomy was performed. In all hybrid procedures, the thoracic phase was conducted in a robot-assisted minimally invasive manner and the abdominal phase was conducted in an open manner due to contraindications for laparoscopic surgery. After resection, all patients underwent a gastric conduit reconstruction (using a posterior mediastinal route). Subsequently, a bilateral thoracic drain was placed. A cervical anastomotic drain was not routinely placed. After surgery, if no pneumothorax occurred, and drain production was less than 200 ml/24 hours the thoracic drains were removed. Fluid management Fluid strategy was aimed at a mildly positive fluid balance of ∼500 mL at the end of the operative procedure. The perfusion status of patients was constantly monitored based on the urine production, mean arterial pressure, and fluid balance. Postoperatively, when mean arterial pressure was below 65 mmHg, or a urine production of less than 0.5 mL/kg/hour volume loading and/or epinephrine administration was initiated. Crystalloids, and/or epinephrine was administered in case of hypoperfusion. However, since excessive fluid administration is a risk factor for the development of respiratory complications after esophageal surgery, this was performed to a limited extent. Outcomes New-onset AF was diagnosed and documented by means of electrocardiography. Standard treatment for AF included amiodarone, digoxin, β-blockade or a combination. Overall infectious complications included pulmonary infections, anastomotic leakage, mediastinitis, thoracic empyema, sepsis, bowel ischemia, abscesses, central line infection, thrombophlebitis, wound infections, urinary tract infections, pericarditis, and endocarditis. Pneumonia was defined by the Uniform Pneumonia Score.13,14 Other pulmonary complications included pleural effusion requiring drainage, pneumothorax requiring treatment, respiratory failure requiring reintubation, acute respiratory distress syndrome, and pleural empyema.15 Anastomotic leakage was defined as a gastrointestinal defect involving esophagus, anastomosis, staple line, or conduit, irrespective of presentation or method of identification.15 Statistical analyses The association between patient and treatment-related characteristics and new-onset AF was studied univariably. Depending on the cell count, the chi-square or Fisher's exact test was used for categorical variables (i.e., a cell count ≤5). The independent samples t-test or Mann-Whitney U test were used for normally or skewed distributed continuous variables, respectively. All continuous data were presented as mean (±standard deviation) or median (interquartile range) and categorical data were presented as number (percentage). The association between new-onset AF and other infectious complications was studied in an univariable and multivariable logistic regression model. Variables to be entered into the multivariable logistic regression model along with new-onset AF were based on clinical reasoning and literature review as well as univariable analysis, to be able to assess whether new-onset AF was independently and significantly associated with the occurrence of these infectious complications. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and Wald test statistic P-values were calculated. Furthermore, the time interval between day of AF diagnosis and other complications was analyzed. Statistical analysis was performed using the SPSS version 21.0 software (IBM Corp., Armonk, NY). P-values < 0.05 were considered statistically significant. RESULTS Patients Among 479 patients that underwent esophagectomy for esophageal or gastroesophageal junction cancer with curative intent, 24 patients were excluded (Fig. 1). Patient and treatment-related characteristics of the final study population of 455 patients are shown in Table 1. Fig. 1 View largeDownload slide Flowchart. Other = pericarditis or endocarditis. Other = Recurrent laryngeal nerve palsy, pulmonary embolism, hypotension. AF, atrial fibrillation, ASA, American Society of Anesthesiologists. Fig. 1 View largeDownload slide Flowchart. Other = pericarditis or endocarditis. Other = Recurrent laryngeal nerve palsy, pulmonary embolism, hypotension. AF, atrial fibrillation, ASA, American Society of Anesthesiologists. Table 1 Patient and treatment-related characteristics and their univariable association with the occurrence of new-onset atrial fibrillation after esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Data are n (%), median (IQR) and mean (±SD). †Carcinoma in situ, gastrointestinal stromal tumor, basaloïd squamous cell carcinoma or undifferentiated tumor cells; ‡Value was based on 428 cases; §Value was based on 424 cases. AF, atrial fibriliation; GEJ, gastroesophageal junction; Hybrid, thoracic phase RAMIE, abdominal phase open; OE, open esophagectomy; TH, transhiatal; TT, transthoracic; RAMIE, robot assisted minimally invasive esophagectomy. View Large Table 1 Patient and treatment-related characteristics and their univariable association with the occurrence of new-onset atrial fibrillation after esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Data are n (%), median (IQR) and mean (±SD). †Carcinoma in situ, gastrointestinal stromal tumor, basaloïd squamous cell carcinoma or undifferentiated tumor cells; ‡Value was based on 428 cases; §Value was based on 424 cases. AF, atrial fibriliation; GEJ, gastroesophageal junction; Hybrid, thoracic phase RAMIE, abdominal phase open; OE, open esophagectomy; TH, transhiatal; TT, transthoracic; RAMIE, robot assisted minimally invasive esophagectomy. View Large New-onset AF occurred in 93 (20.4%) patients. No significant differences in patient and treatment-related characteristics between patients with and without AF were observed. The median age (range) of the patients was 65 years (34–84), with 60.0% (274) of patients having an ASA II status. Most patients (329, 72.3%) had an adenocarcinoma. The majority of patients had a distal (159, 34.9%) pT3 (225, 49.5%), pN0 (214, 47.0%) tumor. Robot-assisted minimally invasive esophagectomy (RAMIE) was performed in 265 (58.2%) patients and in 449 (98.7%) patients the cervical anastomosis was hand sewn. Postoperative outcomes The majority of postoperative infectious complications was more frequently observed in patients with AF versus patients without AF: overall infectious complications 77.4% versus 53.6% (P < 0.001), pulmonary complications (pooled) 49.5% versus 33.4% (P = 0.004), pneumonia 41.9% versus 23.5% (P < 0.001), and anastomotic leakage 43.0% versus 21.3% (P < 0.001). Chyle leakage rates did not significantly differ between both groups: 22.6% (AF) versus 17.4% (non-AF) (P = 0.251). In addition, in-hospital or 30-day mortality was significantly higher in patients with AF: 9.7% (AF) versus (vs.) 3.3% (non-AF) (P = 0.009) (Table 2). Median (interquartile range [IQR]) hospital stay was 23 days (15–37) in patients with AF and 15 days (12–22) in patients without AF (P < 0.001). Also median (IQR) intensive care unit stay was significantly increased in patients with AF (3 days (1–10)) when compared to patients without AF (1 day (1–3)) (P < 0.001). Table 2 Morbidity and mortality in patients with and without new-onset atrial fibrillation (AF) following esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Data are n (%) and median (IQR). AF, atrial fibrillation; ICU, intensive care unit. View Large Table 2 Morbidity and mortality in patients with and without new-onset atrial fibrillation (AF) following esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Data are n (%) and median (IQR). AF, atrial fibrillation; ICU, intensive care unit. View Large Median (range) time to development of AF after surgery was 3.0 (0–38) days. As shown in Figure 1, 84 (90.3%) of the patients with new-onset AF developed a second complication. In univariable analysis, new-onset AF was significantly associated with infectious complications (OR 2.97, 95% CI: 1.75–5.04] (Table 3). More specifically, new-onset AF was also associated with pulmonary complications (OR 1.95, 95% CI: 1.23–3.09; Table 4), pneumonia (OR 2.35, 95% CI: 1.46–3.80; Table 5) and anastomotic leakage (OR 2.79, 95% CI: 1.73–4.52; Table 6). Table 3 Results of univariable and multivariable logistic regression analysis for infectious complications following esophagectomy Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 AF, atrial fibrillation; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot-assisted minimally invasive esophagectomy; TH, transhiatal; TT, transthoracic. View Large Table 3 Results of univariable and multivariable logistic regression analysis for infectious complications following esophagectomy Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 AF, atrial fibrillation; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot-assisted minimally invasive esophagectomy; TH, transhiatal; TT, transthoracic. View Large Table 4 Results of univariable and multivariable logistic regression analysis for pulmonary complications following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 4 Results of univariable and multivariable logistic regression analysis for pulmonary complications following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 5 Results of univariable and multivariable logistic regression analysis for pneumonia following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 5 Results of univariable and multivariable logistic regression analysis for pneumonia following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 6 Results of univariable and multivariable logistic regression analysis for anastomotic leakage following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 AF, atrial fibrillation, ASA, American Society of Anesthesiologists; BMI, body mass index; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot assisted minimally invasive; TH, transhiatal; TT, transthoracic.esophagectomy, . View Large Table 6 Results of univariable and multivariable logistic regression analysis for anastomotic leakage following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 AF, atrial fibrillation, ASA, American Society of Anesthesiologists; BMI, body mass index; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot assisted minimally invasive; TH, transhiatal; TT, transthoracic.esophagectomy, . View Large New-onset AF remained independently and significantly associated with these complications in multivariable analyses when adjusting for the factors as presented in Tables 3 to 8: OR 3.00, 95% CI: 1.73–5.21, for infectious complications, (Table 3); OR 2.06, 95% CI: 1.29–3.30 for pulmonary complications (Table 4); 2.41, 95% CI: 1.48–3.91 for pneumonia (Table 5) and OR 3.00, 95% CI: 1.80–4.99 for anastomotic leakage (Table 6). AF either followed pneumonia closely (with a median (range) of 0.5 (−11–25) days) or occurred concurrently. Contrarily, the diagnosis of anastomotic leakage was preceded by AF with a median (range) of 4.0 (−7.0–19) days in patients with AF. In multivariable analyses within the AF subgroup a significant association was observed between the CRP value at day of AF diagnosis and pneumonia [1.01 (1.00–1.01), P = 0.046] (Table 7), and anastomotic leakage [1.01(1.00–1.01), P = 0.011] (Table 8). Table 7 Predictive factors for pneumonia in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive protein. View Large Table 7 Predictive factors for pneumonia in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive protein. View Large Table 8 Predictive factors for anastomotic leakage in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive Protein; OE, open esophagectomy; MIE, minimally invasive esophagectomy, RAMIE, robot assisted minimally invasive esophagectomy, TH, transhiatal; TT, transthoracic. View Large Table 8 Predictive factors for anastomotic leakage in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive Protein; OE, open esophagectomy; MIE, minimally invasive esophagectomy, RAMIE, robot assisted minimally invasive esophagectomy, TH, transhiatal; TT, transthoracic. View Large DISCUSSION This study demonstrates an association between new-onset AF after esophagectomy and postoperative infectious complications in general, and more specifically with pulmonary complications (pooled), pneumonia and anastomotic leakage in a large prospective database from a high volume center. In addition, the time interval between the day of AF diagnosis and the development of anastomotic leakage and pneumonia was studied, revealing the potential predictive value of new-onset AF for anastomotic leakage since the diagnosis of anastomotic leakage is preceded by new-onset AF with a median of 4 days. These findings could aid the early clinical diagnosis and treatment of infectious complications after esophagectomy. At present, mortality rates in high-volume centers are usually less than 5%.16–18 However, postoperative complication rates remain relatively high when compared to other elective surgical procedures for cancer. This highlights the importance of further recognizing and reducing complications after esophagectomy for cancer.1,3,4 The incidence of new-onset AF after esophagectomy in this study was 20.4%, which is in line with previously published studies reporting incidences of 10–37%.6,8,10,11,19,20 The association between the preoperative variables age, cardiac comorbidity, and neoadjuvant therapy and AF have been consistent. This study rather reported on the risk of developing postoperative complications when new-onset AF occurs after surgery, than on variables potentially predicting AF after esophagectomy. Nevertheless, a trend for developing AF after surgery with increasing age could be identified (Table 1). This study demonstrated that only 9 (9.7%) out of 93 of patients developing AF after esophagectomy had no other postoperative complications. This is consistent with a recent study by Mc Cormack et al.11 in which less than 20% of new-onset AF after esophagectomy was seen without other complications. These findings support the hypothesis that AF is associated with other postoperative infectious complications in the majority of cases. However, since that study focussed on associations rather than causal relations, the question remained whether new-onset AF is causative for, or a consequence of other postoperative complications. During transthoracic esophagectomy, the pleural surfaces and pericardium are exposed. This may lead to direct trauma to the atrium and autonomic nerve fibers, potentially resulting in AF. In addition, intraoperative single lung ventilation may cause oxidative stress, which is linked to AF through mitochondrial dysfunction.21 AF increases the risk of embolic events and hemodynamic instability, potentially leading to organ hypoperfusion and increasing the likelihood of secondary complications.11 However, infection may also cause oxidative stress. The diagnosis of pneumonia was concurrent with, or followed the day diagnosis of new-onset AF closely. Previous research by Stawicki et al.10 reported the same temporal relationship. Due to this relation it may be hypothesized that AF is rather an expression of pulmonary complications than a cause. The association between AF and anastomotic leakage remains a topic of debate. Although several studies showed a significant association,6,8,10 a recently published study showed no association between AF and anastomotic leakage.11 The absence of an significant association between AF and anastomotic leakage in the latter study could be explained by the low statistical power of the study, which is reflected by the low number of events (29 cases of anastomotic leakage). In another study, 156 patients were studied of which 32 (20.5%) developed new-onset AF after esophagectomy. New-onset AF was significantly associated with anastomotic leakage in univariable analysis, however this association ceased to exist in multivariable analysis.10 This could be due to a small sample size, rather than to a true absence of an association. Interestingly, the median time between new-onset AF and the clinical diagnosis of anastomotic leakage was 4 days, exactly the same as observed in the current study. This suggests that AF may be a surrogate marker for anastomotic leakage and could therefore be of clinical importance. To further explore the predictive value of AF for developing other postoperative complications multivariable analyses were conducted within the group of patients who developed AF. (Tables 7 and 8) The height of serum CRP levels showed to be associated with the development of anastomotic leakage and pneumonia. Therefore increased CRP levels at the day of AF diagnosis is an additional warning sign for the development of postoperative pneumonia and anastomotic leakage in patient with AF. Several randomized controlled trials have investigated the effect of prophylactic treatment of new-onset AF directly postesophagectomy.22–24 All studies reported lower incidences of new-onset AF in the intervention group compared to the placebo group. Only one of these trials reported data regarding postoperative complications. Ojima et al.22 randomized 100 patients with a 1:1 parallel allocation ratio to either landiolol prophylaxis or placebo. New-onset AF occurred in 15 patients (30%) receiving placebo versus five (10%) receiving landiolol (P =  0.012). Also Clavien-Dindo grade 2 or higher complications occurred significantly more often in the placebo group (30 (60.0%) vs. 20 (40.0%)). However, pneumonia and anastomotic leakage rates did not differ between groups. The major concern with regard to prophylactic treatment of AF is that it may rather be an early warning sign than causative for anastomotic leakage. Prophylactic treatment for AF may mask an early clinical sign of anastomotic leakage, and potentially delays treatment. Furthermore, AF is relatively easy to treat and resolves fast after treatment initiation.10,25,26 Therefore prevention is not indispensable. Certain limitations apply to the current analysis. Some patients had multiple complications after esophagectomy. Therefore, in these patients, one cannot be certain which of these complications was associated with AF. This might have hampered the time interval analyses. Furthermore, it must be noted that a causal relation between AF and infectious complications was not established in the current study. Nevertheless, the current study included a large number of patients from a prospectively kept database and conducted profound statistical analyses. In conclusion, new-onset AF is rarely seen in isolation and it is highly associated with various postoperative infectious complications. It occurs concurrently with pneumonia, but could function as an early clinical warning sign for anastomotic leakage. Therefore it is advocated to thoroughly evaluate patients who develop new-onset AF after esophagectomy for cancer and not only focus treatment on the restoration of sinus rhythm. Notes Specific author contributions: Conception and design: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve, Richard van Hillegersberg, Jelle P. Ruurda; Administrative support: Maarten F. J. Seesing, Jochem C. G. Scheijmans; Provision of study materials or patients: Jelle P. Ruurda, Richard van Hillegersberg; Collection and assembly of data: Maarten F. J. Seesing, Jochem C. G. Scheijmans; Data analysis and interpretation: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve; Manuscript writing: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve, Richard van Hillegersberg, Jelle P. Ruurda; Final approval of manuscript: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve, Richard van Hillegersberg, Jelle P. Ruurda. References 1 van Hagen P , Hulshof M C , van Lanschot J J et al. Preoperative chemoradiotherapy for esophageal or junctional cancer . N Engl J Med 2012 ; 366 : 2074 – 84 . Google Scholar Crossref Search ADS PubMed 2 Shapiro J , van Lanschot J J , Hulshof M C et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial . Lancet Oncol 2015 ; 16 : 1090 – 8 . Google Scholar Crossref Search ADS PubMed 3 Low D E . Evolution in surgical management of esophageal cancer . Dig Dis 2013 ; 31 : 21 – 29 . Google Scholar Crossref Search ADS PubMed 4 Reynolds J V , Donohoe C L , McGillycuddy E et al. Evolving progress in oncologic and operative outcomes for esophageal and junctional cancer: lessons from the experience of a high-volume center . J Thorac Cardiovasc Surg 2012 ; 143 : 1130 – 7 . e1 . Google Scholar Crossref Search ADS PubMed 5 Blencowe N S , Strong S , McNair A G et al. Reporting of short-term clinical outcomes after esophagectomy . Ann Surg 2012 ; 255 : 658 – 66 . Google Scholar Crossref Search ADS PubMed 6 Stippel D L , Taylan C , Schroder W et al. Supraventricular tachyarrhythmia as early indicator of a complicated course after esophagectomy . Dis Esophagus 2005 ; 18 : 267 – 73 . Google Scholar Crossref Search ADS PubMed 7 Rao V P , Addae-Boateng E , Barua A et al. Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation following oesophagectomy . Eur J Cardiothorac Surg 2012 ; 42 : 438 – 43 . Google Scholar Crossref Search ADS PubMed 8 Murthy S C , Law S , Whooley B P et al. Atrial fibrillation after esophagectomy is a marker for postoperative morbidity and mortality . J Thorac Cardiovasc Surg 2003 ; 126 : 1162 – 7 . Google Scholar Crossref Search ADS PubMed 9 Vaporciyan A A , Correa A M , Rice D C et al. Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients . J Thorac Cardiovasc Surg 2004 ; 127 : 779 – 86 . Google Scholar Crossref Search ADS PubMed 10 Stawicki S P , Prosciak M P , Gerlach A T et al. Atrial fibrillation after esophagectomy: an indicator of postoperative morbidity . Gen Thorac Cardiovasc Surg 2011 ; 59 : 399 – 405 . Google Scholar Crossref Search ADS PubMed 11 Mc Cormack O , Zaborowski A , King S et al. New-onset atrial fibrillation postsurgery for esophageal and junctional cancer . Ann Surg 2014 ; 260 : 772 – 8 . Google Scholar Crossref Search ADS PubMed 12 van der Sluis P C , Ruurda J P , van der Horst S et al. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial) . Trials 2012 ; 13 : 230 . Google Scholar Crossref Search ADS PubMed 13 van der Sluis P C , Verhage R J , van der Horst S et al. A new clinical scoring system to define pneumonia following esophagectomy for cancer . Dig Surg 2014 ; 31 : 108 – 16 . Google Scholar Crossref Search ADS PubMed 14 Weijs T J , Seesing M F , van Rossum P S et al. Internal and external validation of a multivariable model to define hospital-acquired pneumonia after esophagectomy . J Gastrointest Surg 2016 ; 20 : 680 – 7 . Google Scholar Crossref Search ADS PubMed 15 Low D E , Alderson D , Cecconello I et al. International consensus on standardization of data collection for complications associated with esophagectomy . Ann Surg 2015 ; 262 : 286 – 94 . Google Scholar Crossref Search ADS PubMed 16 Modrall J G , Minter R M , Minhajuddin A et al. The surgeon volume-outcome relationship . Ann Surg 2017 ; doi: 10.1097/SLA.0000000000002334 . 17 Nishigori T , Miyata H , Okabe H et al. Impact of hospital volume on risk-adjusted mortality following oesophagectomy in Japan . Br J Surg 2016 ; 103 : 1880 – 6 . Google Scholar Crossref Search ADS PubMed 18 Fuchs H F , Harnsberger C R , Broderick R C et al. Mortality after esophagectomy is heavily impacted by center volume: retrospective analysis of the nationwide inpatient sample . Surg Endosc 2017 ; 31 : 2491 – 7 . Google Scholar Crossref Search ADS PubMed 19 Amar D , Burt M E , Bains M S et al. Symptomatic tachydysrhythmias after esophagectomy: incidence and outcome measures . Ann Thorac Surg 1996 ; 61 : 1506 – 9 . Google Scholar Crossref Search ADS PubMed 20 Mathisen D J , Grillo H C , Wilkins E W Jr et al. Transthoracic esophagectomy: a safe approach to carcinoma of the esophagus . Ann Thorac Surg 1988 ; 45 : 137 – 43 . Google Scholar Crossref Search ADS PubMed 21 Montaigne D , Marechal X , Lefebvre P et al. Mitochondrial dysfunction as an arrhythmogenic substrate . J Am Coll Cardiol 2013 ; 62 : 1466 – 73 . Google Scholar Crossref Search ADS PubMed 22 Ojima T , Nakamori M , Nakamura M et al. Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer . Br J Surg 2017 ; 104 : 1003 – 9 . Google Scholar Crossref Search ADS PubMed 23 Tisdale J E , Wroblewski H A , Wall D S et al. A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy . J Thorac Cardiovasc Surg 2010 ; 140 : 45 – 51 . Google Scholar Crossref Search ADS PubMed 24 Horikoshi Y , Goyagi T , Kudo R et al. The suppressive effects of landiolol administration on the occurrence of postoperative atrial fibrillation and tachycardia, and plasma IL-6 elevation in patients undergoing esophageal surgery: A randomized controlled clinical trial . J Clin Anesth 2017 ; 38 : 111 – 6 . Google Scholar Crossref Search ADS PubMed 25 Chin J H , Moon Y J , Jo J Y et al. Association between postoperatively developed atrial fibrillation and long-term mortality after esophagectomy in esophageal cancer patients: an observational study . PLoS One 2016 ; 11 : e0154931 . Google Scholar Crossref Search ADS PubMed 26 Bobbio A , Caporale D , Internullo E et al. Postoperative outcome of patients undergoing lung resection presenting with new-onset atrial fibrillation managed by amiodarone or diltiazem . Eur J Cardiothorac Surg 2007 ; 31 : 70 – 74 . Google Scholar Crossref Search ADS PubMed © The Author(s) 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/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diseases of the Esophagus Oxford University Press

The predictive value of new-onset atrial fibrillation on postoperative morbidity after esophagectomy

Loading next page...
1
 
/lp/ou_press/the-predictive-value-of-new-onset-atrial-fibrillation-on-postoperative-jHPkmIUnYU
Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.
ISSN
1120-8694
eISSN
1442-2050
D.O.I.
10.1093/dote/doy028
Publisher site
See Article on Publisher Site

Abstract

SUMMARY New-onset atrial fibrillation (AF) is frequently observed following esophagectomy and may predict other complications. The aim of the current study was to determine the association between, and the possible predictive value of, new-onset AF and infectious complications following esophagectomy. Consecutive patients who underwent elective esophagectomy with curative intent for esophageal cancer between 2004 and 2016 in the University Medical Center Utrecht were included from a prospective database. The date of diagnosis of the complications included in the current analysis was retrospectively collected from the computerized medical record. The association between new-onset AF and infectious complications was studied in univariable and multivariable logistic regression analyses. A total of 455 patients were included. In 93 (20.4%) patients new-onset AF was encountered after esophagectomy. There were no significant differences in patient and treatment-related characteristics between the patients with and without AF. In 9 (9.7%) patients, AF was the only adverse event following surgery. In multivariable analyses, AF was significantly associated with infectious complications in general (OR 3.00, 95% CI: 1.73–5.21). More specifically, AF was associated with pulmonary complications (OR 2.06, 95% CI: 1.29–3.30), pneumonia (OR 2.41, 95% CI: 1.48–3.91) and anastomotic leakage (OR 3.00, 95% CI: 1.80–4.99). In patients who underwent esophagectomy, new-onset AF was highly associated with infectious complications. AF may serve as an early clinical warning sign for anastomotic leakage. Therefore, further evaluation of patients who develop new-onset AF after esophagectomy is warranted. INTRODUCTION Curative treatment for patients with resectable locally advanced esophageal cancer consists of neoadjuvant chemoradiotherapy followed by esophagectomy with en-bloc lymphadenectomy.1,2 Although mortality following esophagectomy steadily decreased over the past years, morbidity rates remain high compared to other elective cancer surgery.1,3,4 The most frequently encountered postoperative complications include pulmonary complications (12–46%), anastomotic leakage (0–35%), and atrial fibrillation (AF) (12–37%).1,5–10 AF increases the risk of embolic events and hemodynamic instability, potentially resulting in organ hypoperfusion.11 Although the exact pathophysiology of new-onset AF after esophagectomy remains unclear, several retrospective studies demonstrated a significant association between new-onset AF and other postoperative complications.6,8,10 Therefore, it was hypothesized that AF could be of clinical predictive value if AF was shown to precede other postoperative complications. Although the most recent and largest study published to date confirms the association between new-onset AF after esophagectomy and pulmonary complications, it did not demonstrate a significant relation between AF and anastomotic leakage.11 The aim of this study is to determine the association between, and the possible predictive value of, new-onset AF and infectious complications following esophagectomy, with a focus on the 2 most frequently encountered complications after esophagectomy, namely pulmonary complications and anastomotic leakage. METHODS Patients Consecutive patients who underwent an elective esophagectomy for esophageal or gastroesophageal junction cancer with curative intent between 2004 and 2016 at the University Medical Center (UMC) Utrecht were included in this study. Exclusion criteria included preoperative presence of AF and American Association of Anaesthesiologists (ASA) IV classification. Patients included in this study were not given routine AF prophylaxis postoperatively. Patient and treatment-related characteristics as well as surgical outcome data were prospectively recorded in an Institutional Review Board (IRB) approved database. The date of diagnosis of the complications included in the current analysis was retrospectively collected from the computerized medical record. C-reactive protein (CRP) levels were registered at the day of AF diagnosis. This study was approved by the Medical Ethics Review Committee of the UMC Utrecht (IRB-number 13–061/C), and informed consent was waived. Surgical approach The standard surgical approach for esophageal cancer at the UMC Utrecht was a transthoracic robot-assisted minimally invasive esophagectomy. However, some patients underwent an open transthoracic esophagectomy, since they were included in the ROBOT trial.12 When a patient was considered to be too frail to be eligible for a transthoracic approach, a (minimally invasive) transhiatal esophagectomy was performed. In all hybrid procedures, the thoracic phase was conducted in a robot-assisted minimally invasive manner and the abdominal phase was conducted in an open manner due to contraindications for laparoscopic surgery. After resection, all patients underwent a gastric conduit reconstruction (using a posterior mediastinal route). Subsequently, a bilateral thoracic drain was placed. A cervical anastomotic drain was not routinely placed. After surgery, if no pneumothorax occurred, and drain production was less than 200 ml/24 hours the thoracic drains were removed. Fluid management Fluid strategy was aimed at a mildly positive fluid balance of ∼500 mL at the end of the operative procedure. The perfusion status of patients was constantly monitored based on the urine production, mean arterial pressure, and fluid balance. Postoperatively, when mean arterial pressure was below 65 mmHg, or a urine production of less than 0.5 mL/kg/hour volume loading and/or epinephrine administration was initiated. Crystalloids, and/or epinephrine was administered in case of hypoperfusion. However, since excessive fluid administration is a risk factor for the development of respiratory complications after esophageal surgery, this was performed to a limited extent. Outcomes New-onset AF was diagnosed and documented by means of electrocardiography. Standard treatment for AF included amiodarone, digoxin, β-blockade or a combination. Overall infectious complications included pulmonary infections, anastomotic leakage, mediastinitis, thoracic empyema, sepsis, bowel ischemia, abscesses, central line infection, thrombophlebitis, wound infections, urinary tract infections, pericarditis, and endocarditis. Pneumonia was defined by the Uniform Pneumonia Score.13,14 Other pulmonary complications included pleural effusion requiring drainage, pneumothorax requiring treatment, respiratory failure requiring reintubation, acute respiratory distress syndrome, and pleural empyema.15 Anastomotic leakage was defined as a gastrointestinal defect involving esophagus, anastomosis, staple line, or conduit, irrespective of presentation or method of identification.15 Statistical analyses The association between patient and treatment-related characteristics and new-onset AF was studied univariably. Depending on the cell count, the chi-square or Fisher's exact test was used for categorical variables (i.e., a cell count ≤5). The independent samples t-test or Mann-Whitney U test were used for normally or skewed distributed continuous variables, respectively. All continuous data were presented as mean (±standard deviation) or median (interquartile range) and categorical data were presented as number (percentage). The association between new-onset AF and other infectious complications was studied in an univariable and multivariable logistic regression model. Variables to be entered into the multivariable logistic regression model along with new-onset AF were based on clinical reasoning and literature review as well as univariable analysis, to be able to assess whether new-onset AF was independently and significantly associated with the occurrence of these infectious complications. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and Wald test statistic P-values were calculated. Furthermore, the time interval between day of AF diagnosis and other complications was analyzed. Statistical analysis was performed using the SPSS version 21.0 software (IBM Corp., Armonk, NY). P-values < 0.05 were considered statistically significant. RESULTS Patients Among 479 patients that underwent esophagectomy for esophageal or gastroesophageal junction cancer with curative intent, 24 patients were excluded (Fig. 1). Patient and treatment-related characteristics of the final study population of 455 patients are shown in Table 1. Fig. 1 View largeDownload slide Flowchart. Other = pericarditis or endocarditis. Other = Recurrent laryngeal nerve palsy, pulmonary embolism, hypotension. AF, atrial fibrillation, ASA, American Society of Anesthesiologists. Fig. 1 View largeDownload slide Flowchart. Other = pericarditis or endocarditis. Other = Recurrent laryngeal nerve palsy, pulmonary embolism, hypotension. AF, atrial fibrillation, ASA, American Society of Anesthesiologists. Table 1 Patient and treatment-related characteristics and their univariable association with the occurrence of new-onset atrial fibrillation after esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Data are n (%), median (IQR) and mean (±SD). †Carcinoma in situ, gastrointestinal stromal tumor, basaloïd squamous cell carcinoma or undifferentiated tumor cells; ‡Value was based on 428 cases; §Value was based on 424 cases. AF, atrial fibriliation; GEJ, gastroesophageal junction; Hybrid, thoracic phase RAMIE, abdominal phase open; OE, open esophagectomy; TH, transhiatal; TT, transthoracic; RAMIE, robot assisted minimally invasive esophagectomy. View Large Table 1 Patient and treatment-related characteristics and their univariable association with the occurrence of new-onset atrial fibrillation after esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) Sex Female 67 (20.0) 268 (80.0) 0.698 Male 26 (21.7) 94 (78.3) Age, years (mean ± SD) 65 ± 8 63 ± 9 0.084 BMI, kg/m2 (mean ± SD) 25 ± 4 26 ± 4 0.663 ASA classification I 17 (18.3) 91 (25.1) 0.242 II 60 (64.5) 214 (59.1) III 16 (17.2) 57 (15.7) Comorbidities Pulmonary 22 (23.7) 83 (22.9) 0.882 Cardiac 22 (23.7) 77 (21.3) 0.619 Vascular 41 (44.1) 125 (34.5) 0.088 Diabetes mellitus 9 (9.7) 52 (14.4) 0.237 Histology AC 65 (69.9) 264 (72.9) 0.422 SCC 22 (23.7 91 (25.1) Other† 6 (6.5) 7 (1.9) (y)pT stage T0 16 (17.2) 53 (14.6) 0.978 T1 11 (11.8) 62 (17.1) T2 16 (17.2) 46 (12.7) T3 43 (46.2) 182 (50.3) T4 6 (6.5) 17 (4.7) In situ 1 (1.1) 2 (0.6) (y)pN stage N0 53(57.0) 161 (44.5) 0.167 N1 16 (17.2) 100 (27.6) N2 11 (11.8) 68 (18.8) N3 13 (14.0) 33 (9.1) Location of tumor Cervical 2 (2.2) 3 (0.8) 0.320 Proximal 4 (4.3) 9 (2.5) Middle 9 (9.7) 54 (14.9) Distal 40 (43.0) 119 (32.9) GEJ 38 (40.9) 177 (48.9) Neoadjuvant treatment No 30 (32.3) 137 (37.8) 0.225 Chemotherapy 25 (26.9) 99 (27.3) Radiotherapy 0 (0) 1 (0.3) Chemoradiotherapy 38 (40.9) 125 (34.5) Surgical approach TT RAMIE 49 (52.7) 216 (59.7) 0.075 TT OE 18 (19.4) 39 (10.8) TH MIE 12 (12.9) 65 (18.0) TH OE 12 (12.9) 35 (9.7) Hybrid 2 (2.2) 7 (1.9) Location of anastomosis Cervical 91 (97.8) 358 (98.9) 0.431 Intrathoracic 2 (2.2) 4 (1.1) Duration of surgery, min‡ (mean ± SD) 363 ± 101 368 ± 94 0.663 Intraoperative bloodloss, mL§ (median, IQR) 370 (370) 320 (450) 0.366 Data are n (%), median (IQR) and mean (±SD). †Carcinoma in situ, gastrointestinal stromal tumor, basaloïd squamous cell carcinoma or undifferentiated tumor cells; ‡Value was based on 428 cases; §Value was based on 424 cases. AF, atrial fibriliation; GEJ, gastroesophageal junction; Hybrid, thoracic phase RAMIE, abdominal phase open; OE, open esophagectomy; TH, transhiatal; TT, transthoracic; RAMIE, robot assisted minimally invasive esophagectomy. View Large New-onset AF occurred in 93 (20.4%) patients. No significant differences in patient and treatment-related characteristics between patients with and without AF were observed. The median age (range) of the patients was 65 years (34–84), with 60.0% (274) of patients having an ASA II status. Most patients (329, 72.3%) had an adenocarcinoma. The majority of patients had a distal (159, 34.9%) pT3 (225, 49.5%), pN0 (214, 47.0%) tumor. Robot-assisted minimally invasive esophagectomy (RAMIE) was performed in 265 (58.2%) patients and in 449 (98.7%) patients the cervical anastomosis was hand sewn. Postoperative outcomes The majority of postoperative infectious complications was more frequently observed in patients with AF versus patients without AF: overall infectious complications 77.4% versus 53.6% (P < 0.001), pulmonary complications (pooled) 49.5% versus 33.4% (P = 0.004), pneumonia 41.9% versus 23.5% (P < 0.001), and anastomotic leakage 43.0% versus 21.3% (P < 0.001). Chyle leakage rates did not significantly differ between both groups: 22.6% (AF) versus 17.4% (non-AF) (P = 0.251). In addition, in-hospital or 30-day mortality was significantly higher in patients with AF: 9.7% (AF) versus (vs.) 3.3% (non-AF) (P = 0.009) (Table 2). Median (interquartile range [IQR]) hospital stay was 23 days (15–37) in patients with AF and 15 days (12–22) in patients without AF (P < 0.001). Also median (IQR) intensive care unit stay was significantly increased in patients with AF (3 days (1–10)) when compared to patients without AF (1 day (1–3)) (P < 0.001). Table 2 Morbidity and mortality in patients with and without new-onset atrial fibrillation (AF) following esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Data are n (%) and median (IQR). AF, atrial fibrillation; ICU, intensive care unit. View Large Table 2 Morbidity and mortality in patients with and without new-onset atrial fibrillation (AF) following esophagectomy Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Characteristic AF (N = 93) No AF (N = 362) P-value N (%) N (%) In-hospital or 30-day mortality, days (median, IQR) 9 (9.7) 12 (3.3) 0.009 Hospital stay, days (median, IQR) 23 (15–37) 15 (12–22) <0.001 ICU stay, days (median, IQR) 3 (1–10) 1 (1–3) <0.001 Postoperative complication N/A 243 (67.1) N/A Reintervention 35 (44.3) 80 (26.5) 0.002 Surgical complications 60 (64.5) 170 (47.0) 0.003 Infectious complications 72 (77.4) 194 (53.6) <0.001 Pneumonia 39 (41.9) 85 (23.5) <0.001 Pulmonary embolus 10 (10.8) 9 (2.5) <0.001 Any pulmonary complications 46 (49.5) 121 (33.4) 0.004 Anastomotic leak/conduit necrosis 40 (43.0) 77 (21.3) <0.001 Chyle leak 21 (22.6) 63 (17.4) 0.251 Myocardial infarction 0 (0) 3 (0.8) 0.378 Data are n (%) and median (IQR). AF, atrial fibrillation; ICU, intensive care unit. View Large Median (range) time to development of AF after surgery was 3.0 (0–38) days. As shown in Figure 1, 84 (90.3%) of the patients with new-onset AF developed a second complication. In univariable analysis, new-onset AF was significantly associated with infectious complications (OR 2.97, 95% CI: 1.75–5.04] (Table 3). More specifically, new-onset AF was also associated with pulmonary complications (OR 1.95, 95% CI: 1.23–3.09; Table 4), pneumonia (OR 2.35, 95% CI: 1.46–3.80; Table 5) and anastomotic leakage (OR 2.79, 95% CI: 1.73–4.52; Table 6). Table 3 Results of univariable and multivariable logistic regression analysis for infectious complications following esophagectomy Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 AF, atrial fibrillation; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot-assisted minimally invasive esophagectomy; TH, transhiatal; TT, transthoracic. View Large Table 3 Results of univariable and multivariable logistic regression analysis for infectious complications following esophagectomy Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 Univariable Analysis Multivariable Analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.04 0.103 1.01 0.99–1.04 0.250 ASA I Reference Reference II 0.89 0.57–1.40 0.612 0.72 0.44–1.17 0.183 III 1.66 0.88–3.11 0.116 1.35 0.66–2.74 0.410 BMI 1.04 0.99–1.09 0.056 1.06 1.01–1.12 0.017 Preoperative vascular comorbidity 1.04 0.70–1.53 0.850 Not included Preoperative cardiac comorbidity 1.18 0.75–1.87 0.472 Not included Preoperative diabetes 1.30 0.75–2.28 0.352 1.16 0.62–2.14 0.647 Preoperative pulmonary comorbidity 1.57 0.99–2.48 0.053 1.69 1.03–2.77 0.039 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.73 0.46-1.17 0.193 Chemoradiotherapy 1.15 0.74-1.79 0.540 Surgical approach TT RAMIE reference Reference TT OE 1.66 0.90-3.05 0.102 1.28 0.67–2.43 0.451 TH MIE 0.97 0.58-1.62 0.906 0.93 0.53–1.62 0.784 TH OE 0.95 0.51-1.77 0.870 0.88 0.46–1.72 0.715 Hybrid 6.13 0.76-49.74 0.089 6.17 0.73–52.23 0.095 Intrathoracic anastomosis (versus cervical) 1.43 0.26-7.87 0.683 Not included Postoperative chyle leakage 2.15 1.28-3.62 0.004 2.27 1.30–3.96 0.004 Postoperative AF 2.97 1.75-5.04 <0.001 3.00 1.73–5.21 <0.001 AF, atrial fibrillation; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot-assisted minimally invasive esophagectomy; TH, transhiatal; TT, transthoracic. View Large Table 4 Results of univariable and multivariable logistic regression analysis for pulmonary complications following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 4 Results of univariable and multivariable logistic regression analysis for pulmonary complications following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98-1.03 0.630 ASA I Reference Reference II 0.83 0.52–1.31 0.418 0.80 0.50–1.28 0.341 III 1.43 0.78–2.60 0.249 1.31 0.70–2.44 0.394 BMI 0.99 0.95–1.04 0.772 Pulmonary comorbidity 1.20 0.77–1.88 0.425 1.17 0.73–1.85 0.516 Recurrent laryngeal nerve damage 2.03 1.10–3.75 0.024 2.11 1.13–3.93 0.019 Postoperative AF 1.95 1.23–3.09 0.005 2.06 1.29–3.30 0.002 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 5 Results of univariable and multivariable logistic regression analysis for pneumonia following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 5 Results of univariable and multivariable logistic regression analysis for pneumonia following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.01 0.98–1.03 0.572 Not included ASA I Reference Reference II 1.07 0.64-1.78 0.798 0.98 0.58–1.66 0.948 III 1.56 0.82–3.00 0.179 1.35 0.69–2.64 0.389 BMI 1.01 0.97–1.06 0.613 Not included Pulmonary comorbidity 1.55 0.97–2.49 0.066 1.51 0.93–2.46 0.095 Recurrent laryngeal nerve damage 1.33 0.69–2.56 0.391 1.44 0.74–2.81 0.283 Postoperative AF 2.35 1.46–3.80 <0.001 2.41 1.48–3.91 <0.001 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index. View Large Table 6 Results of univariable and multivariable logistic regression analysis for anastomotic leakage following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 AF, atrial fibrillation, ASA, American Society of Anesthesiologists; BMI, body mass index; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot assisted minimally invasive; TH, transhiatal; TT, transthoracic.esophagectomy, . View Large Table 6 Results of univariable and multivariable logistic regression analysis for anastomotic leakage following esophagectomy Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.99–1.05 0.092 1.01 0.98–1.04 0.535 ASA I Reference Reference II 1.13 0.67–1.93 0.645 0.89 0.50–1.58 0.686 III 1.94 1.00–3.75 0.050 1.39 0.66–2.95 0.390 BMI 1.02 0.97–1.07 0.558 Not included Preoperative vascular comorbidity 1.18 0.76–1.81 0.460 Not included Preoperative cardiac comorbidity 1.04 0.63–1.72 0.888 Not included Preoperative diabetes 1.50 0.84–2.67 0.176 1.46 0.77–2.76 0.390 Preoperative pulmonary comorbidity 1.95 1.22–3.11 0.006 1.81 1.09–3.00 0.021 Neoadjuvant therapy No Reference Not included Radiotherapy N = 1 Chemotherapy 0.83 0.48–1.44 0.503 Chemoradiotherapy 1.21 0.74–1.96 0.451 Surgical approach TT RAMIE Reference Reference TT OE 0.87 0.44–1.75 0.703 0.70 0.34–1.44 0.329 TH MIE 1.77 1.02–3.06 0.041 1.78 0.97–3.25 0.062 TH OE 1.39 0.70–2.76 0.348 1.37 0.66–2.84 0.399 Hybrid 0.94 0.19–4.62 0.935 0.97 0.18–5.26 0.973 Intrathoracic anastomosis (versus cervical) 1.45 0.26–8.03 0.669 Not included Postoperative chyle leakage 1.70 1.02–2.82 0.042 1.89 1.09–3.29 0.024 Postoperative AF 2.79 1.73–4.52 <0.001 3.00 1.80–4.99 <0.001 AF, atrial fibrillation, ASA, American Society of Anesthesiologists; BMI, body mass index; MIE, minimally invasive esophagectomy; OE, open esophagectomy; RAMIE, robot assisted minimally invasive; TH, transhiatal; TT, transthoracic.esophagectomy, . View Large New-onset AF remained independently and significantly associated with these complications in multivariable analyses when adjusting for the factors as presented in Tables 3 to 8: OR 3.00, 95% CI: 1.73–5.21, for infectious complications, (Table 3); OR 2.06, 95% CI: 1.29–3.30 for pulmonary complications (Table 4); 2.41, 95% CI: 1.48–3.91 for pneumonia (Table 5) and OR 3.00, 95% CI: 1.80–4.99 for anastomotic leakage (Table 6). AF either followed pneumonia closely (with a median (range) of 0.5 (−11–25) days) or occurred concurrently. Contrarily, the diagnosis of anastomotic leakage was preceded by AF with a median (range) of 4.0 (−7.0–19) days in patients with AF. In multivariable analyses within the AF subgroup a significant association was observed between the CRP value at day of AF diagnosis and pneumonia [1.01 (1.00–1.01), P = 0.046] (Table 7), and anastomotic leakage [1.01(1.00–1.01), P = 0.011] (Table 8). Table 7 Predictive factors for pneumonia in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive protein. View Large Table 7 Predictive factors for pneumonia in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.02 0.97–1.07 0.498 Not included ASA I Reference Reference II 0.38 0.13–1.14 0.083 0.24 0.07–0.83 0.025 III 0.70 0.18–2.77 0.611 0.48 0.10–2.34 0.369 BMI 1.06 0.96–1.17 0.265 Not included Pulmonary comorbidity 0.95 0.36–2.50 0.911 0.65 0.21–1.98 0.448 Recurrent laryngeal nerve damage 0.68 0.18–3.89 0.661 Not included CRP at diagnosis AF 1.01 1.00–1.01 0.026 1.01 1.00–1.01 0.046 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive protein. View Large Table 8 Predictive factors for anastomotic leakage in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive Protein; OE, open esophagectomy; MIE, minimally invasive esophagectomy, RAMIE, robot assisted minimally invasive esophagectomy, TH, transhiatal; TT, transthoracic. View Large Table 8 Predictive factors for anastomotic leakage in patients with AF (N = 93) Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 Univariable analysis Multivariable analysis Variable OR 95% CI P OR 95% CI P Age 1.06 1.00–1.11 0.048 1.06 0.99–1.12 0.054 ASA I Reference Not included II 1.50 0.49–4.58 0.477 III 1.43 0.35–5.79 0.620 BMI 0.94 0.85–1.03 0.189 Not included Preoperative vascular comorbidity 1.28 0.56–2.91 0.565 Not included Preoperative cardiac comorbidity 1.45 0.55–3.78 0.450 Not included Preoperative diabetes 1.07 0.28–4.26 0.927 Not included Preoperative pulmonary comorbidity 1.84 0.70–4.84 0.214 Not included Neoadjuvant therapy No Reference Not included Chemotherapy 1.85 0.62–5.50 0.271 Chemoradiotherapy 1.80 0.67–4.85 0.245 Surgical approach TT RAMIE Reference TT OE 0.35 0.10–1.22 0.099 TH MIE 2.46 0.65–9.24 0.184 TH OE 0.88 0.24–3.15 0.840 Hybrid 1.23 0.07–20.76 0.887 Surgical approach OE 0.47 0.19–1.16 0.100 0.41 0.15–1.12 0.082 CRP at diagnosis AF 1.01 1.00–1.01 0.020 1.01 1.00–1.01 0.011 AF, atrial fibrillation; ASA, American Society of Anesthesiologists; BMI, body mass index; CRP, C-reactive Protein; OE, open esophagectomy; MIE, minimally invasive esophagectomy, RAMIE, robot assisted minimally invasive esophagectomy, TH, transhiatal; TT, transthoracic. View Large DISCUSSION This study demonstrates an association between new-onset AF after esophagectomy and postoperative infectious complications in general, and more specifically with pulmonary complications (pooled), pneumonia and anastomotic leakage in a large prospective database from a high volume center. In addition, the time interval between the day of AF diagnosis and the development of anastomotic leakage and pneumonia was studied, revealing the potential predictive value of new-onset AF for anastomotic leakage since the diagnosis of anastomotic leakage is preceded by new-onset AF with a median of 4 days. These findings could aid the early clinical diagnosis and treatment of infectious complications after esophagectomy. At present, mortality rates in high-volume centers are usually less than 5%.16–18 However, postoperative complication rates remain relatively high when compared to other elective surgical procedures for cancer. This highlights the importance of further recognizing and reducing complications after esophagectomy for cancer.1,3,4 The incidence of new-onset AF after esophagectomy in this study was 20.4%, which is in line with previously published studies reporting incidences of 10–37%.6,8,10,11,19,20 The association between the preoperative variables age, cardiac comorbidity, and neoadjuvant therapy and AF have been consistent. This study rather reported on the risk of developing postoperative complications when new-onset AF occurs after surgery, than on variables potentially predicting AF after esophagectomy. Nevertheless, a trend for developing AF after surgery with increasing age could be identified (Table 1). This study demonstrated that only 9 (9.7%) out of 93 of patients developing AF after esophagectomy had no other postoperative complications. This is consistent with a recent study by Mc Cormack et al.11 in which less than 20% of new-onset AF after esophagectomy was seen without other complications. These findings support the hypothesis that AF is associated with other postoperative infectious complications in the majority of cases. However, since that study focussed on associations rather than causal relations, the question remained whether new-onset AF is causative for, or a consequence of other postoperative complications. During transthoracic esophagectomy, the pleural surfaces and pericardium are exposed. This may lead to direct trauma to the atrium and autonomic nerve fibers, potentially resulting in AF. In addition, intraoperative single lung ventilation may cause oxidative stress, which is linked to AF through mitochondrial dysfunction.21 AF increases the risk of embolic events and hemodynamic instability, potentially leading to organ hypoperfusion and increasing the likelihood of secondary complications.11 However, infection may also cause oxidative stress. The diagnosis of pneumonia was concurrent with, or followed the day diagnosis of new-onset AF closely. Previous research by Stawicki et al.10 reported the same temporal relationship. Due to this relation it may be hypothesized that AF is rather an expression of pulmonary complications than a cause. The association between AF and anastomotic leakage remains a topic of debate. Although several studies showed a significant association,6,8,10 a recently published study showed no association between AF and anastomotic leakage.11 The absence of an significant association between AF and anastomotic leakage in the latter study could be explained by the low statistical power of the study, which is reflected by the low number of events (29 cases of anastomotic leakage). In another study, 156 patients were studied of which 32 (20.5%) developed new-onset AF after esophagectomy. New-onset AF was significantly associated with anastomotic leakage in univariable analysis, however this association ceased to exist in multivariable analysis.10 This could be due to a small sample size, rather than to a true absence of an association. Interestingly, the median time between new-onset AF and the clinical diagnosis of anastomotic leakage was 4 days, exactly the same as observed in the current study. This suggests that AF may be a surrogate marker for anastomotic leakage and could therefore be of clinical importance. To further explore the predictive value of AF for developing other postoperative complications multivariable analyses were conducted within the group of patients who developed AF. (Tables 7 and 8) The height of serum CRP levels showed to be associated with the development of anastomotic leakage and pneumonia. Therefore increased CRP levels at the day of AF diagnosis is an additional warning sign for the development of postoperative pneumonia and anastomotic leakage in patient with AF. Several randomized controlled trials have investigated the effect of prophylactic treatment of new-onset AF directly postesophagectomy.22–24 All studies reported lower incidences of new-onset AF in the intervention group compared to the placebo group. Only one of these trials reported data regarding postoperative complications. Ojima et al.22 randomized 100 patients with a 1:1 parallel allocation ratio to either landiolol prophylaxis or placebo. New-onset AF occurred in 15 patients (30%) receiving placebo versus five (10%) receiving landiolol (P =  0.012). Also Clavien-Dindo grade 2 or higher complications occurred significantly more often in the placebo group (30 (60.0%) vs. 20 (40.0%)). However, pneumonia and anastomotic leakage rates did not differ between groups. The major concern with regard to prophylactic treatment of AF is that it may rather be an early warning sign than causative for anastomotic leakage. Prophylactic treatment for AF may mask an early clinical sign of anastomotic leakage, and potentially delays treatment. Furthermore, AF is relatively easy to treat and resolves fast after treatment initiation.10,25,26 Therefore prevention is not indispensable. Certain limitations apply to the current analysis. Some patients had multiple complications after esophagectomy. Therefore, in these patients, one cannot be certain which of these complications was associated with AF. This might have hampered the time interval analyses. Furthermore, it must be noted that a causal relation between AF and infectious complications was not established in the current study. Nevertheless, the current study included a large number of patients from a prospectively kept database and conducted profound statistical analyses. In conclusion, new-onset AF is rarely seen in isolation and it is highly associated with various postoperative infectious complications. It occurs concurrently with pneumonia, but could function as an early clinical warning sign for anastomotic leakage. Therefore it is advocated to thoroughly evaluate patients who develop new-onset AF after esophagectomy for cancer and not only focus treatment on the restoration of sinus rhythm. Notes Specific author contributions: Conception and design: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve, Richard van Hillegersberg, Jelle P. Ruurda; Administrative support: Maarten F. J. Seesing, Jochem C. G. Scheijmans; Provision of study materials or patients: Jelle P. Ruurda, Richard van Hillegersberg; Collection and assembly of data: Maarten F. J. Seesing, Jochem C. G. Scheijmans; Data analysis and interpretation: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve; Manuscript writing: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve, Richard van Hillegersberg, Jelle P. Ruurda; Final approval of manuscript: Maarten F. J. Seesing, Jochem C. G. Scheijmans, Alicia S. Borggreve, Richard van Hillegersberg, Jelle P. Ruurda. References 1 van Hagen P , Hulshof M C , van Lanschot J J et al. Preoperative chemoradiotherapy for esophageal or junctional cancer . N Engl J Med 2012 ; 366 : 2074 – 84 . Google Scholar Crossref Search ADS PubMed 2 Shapiro J , van Lanschot J J , Hulshof M C et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial . Lancet Oncol 2015 ; 16 : 1090 – 8 . Google Scholar Crossref Search ADS PubMed 3 Low D E . Evolution in surgical management of esophageal cancer . Dig Dis 2013 ; 31 : 21 – 29 . Google Scholar Crossref Search ADS PubMed 4 Reynolds J V , Donohoe C L , McGillycuddy E et al. Evolving progress in oncologic and operative outcomes for esophageal and junctional cancer: lessons from the experience of a high-volume center . J Thorac Cardiovasc Surg 2012 ; 143 : 1130 – 7 . e1 . Google Scholar Crossref Search ADS PubMed 5 Blencowe N S , Strong S , McNair A G et al. Reporting of short-term clinical outcomes after esophagectomy . Ann Surg 2012 ; 255 : 658 – 66 . Google Scholar Crossref Search ADS PubMed 6 Stippel D L , Taylan C , Schroder W et al. Supraventricular tachyarrhythmia as early indicator of a complicated course after esophagectomy . Dis Esophagus 2005 ; 18 : 267 – 73 . Google Scholar Crossref Search ADS PubMed 7 Rao V P , Addae-Boateng E , Barua A et al. Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation following oesophagectomy . Eur J Cardiothorac Surg 2012 ; 42 : 438 – 43 . Google Scholar Crossref Search ADS PubMed 8 Murthy S C , Law S , Whooley B P et al. Atrial fibrillation after esophagectomy is a marker for postoperative morbidity and mortality . J Thorac Cardiovasc Surg 2003 ; 126 : 1162 – 7 . Google Scholar Crossref Search ADS PubMed 9 Vaporciyan A A , Correa A M , Rice D C et al. Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients . J Thorac Cardiovasc Surg 2004 ; 127 : 779 – 86 . Google Scholar Crossref Search ADS PubMed 10 Stawicki S P , Prosciak M P , Gerlach A T et al. Atrial fibrillation after esophagectomy: an indicator of postoperative morbidity . Gen Thorac Cardiovasc Surg 2011 ; 59 : 399 – 405 . Google Scholar Crossref Search ADS PubMed 11 Mc Cormack O , Zaborowski A , King S et al. New-onset atrial fibrillation postsurgery for esophageal and junctional cancer . Ann Surg 2014 ; 260 : 772 – 8 . Google Scholar Crossref Search ADS PubMed 12 van der Sluis P C , Ruurda J P , van der Horst S et al. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial) . Trials 2012 ; 13 : 230 . Google Scholar Crossref Search ADS PubMed 13 van der Sluis P C , Verhage R J , van der Horst S et al. A new clinical scoring system to define pneumonia following esophagectomy for cancer . Dig Surg 2014 ; 31 : 108 – 16 . Google Scholar Crossref Search ADS PubMed 14 Weijs T J , Seesing M F , van Rossum P S et al. Internal and external validation of a multivariable model to define hospital-acquired pneumonia after esophagectomy . J Gastrointest Surg 2016 ; 20 : 680 – 7 . Google Scholar Crossref Search ADS PubMed 15 Low D E , Alderson D , Cecconello I et al. International consensus on standardization of data collection for complications associated with esophagectomy . Ann Surg 2015 ; 262 : 286 – 94 . Google Scholar Crossref Search ADS PubMed 16 Modrall J G , Minter R M , Minhajuddin A et al. The surgeon volume-outcome relationship . Ann Surg 2017 ; doi: 10.1097/SLA.0000000000002334 . 17 Nishigori T , Miyata H , Okabe H et al. Impact of hospital volume on risk-adjusted mortality following oesophagectomy in Japan . Br J Surg 2016 ; 103 : 1880 – 6 . Google Scholar Crossref Search ADS PubMed 18 Fuchs H F , Harnsberger C R , Broderick R C et al. Mortality after esophagectomy is heavily impacted by center volume: retrospective analysis of the nationwide inpatient sample . Surg Endosc 2017 ; 31 : 2491 – 7 . Google Scholar Crossref Search ADS PubMed 19 Amar D , Burt M E , Bains M S et al. Symptomatic tachydysrhythmias after esophagectomy: incidence and outcome measures . Ann Thorac Surg 1996 ; 61 : 1506 – 9 . Google Scholar Crossref Search ADS PubMed 20 Mathisen D J , Grillo H C , Wilkins E W Jr et al. Transthoracic esophagectomy: a safe approach to carcinoma of the esophagus . Ann Thorac Surg 1988 ; 45 : 137 – 43 . Google Scholar Crossref Search ADS PubMed 21 Montaigne D , Marechal X , Lefebvre P et al. Mitochondrial dysfunction as an arrhythmogenic substrate . J Am Coll Cardiol 2013 ; 62 : 1466 – 73 . Google Scholar Crossref Search ADS PubMed 22 Ojima T , Nakamori M , Nakamura M et al. Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer . Br J Surg 2017 ; 104 : 1003 – 9 . Google Scholar Crossref Search ADS PubMed 23 Tisdale J E , Wroblewski H A , Wall D S et al. A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy . J Thorac Cardiovasc Surg 2010 ; 140 : 45 – 51 . Google Scholar Crossref Search ADS PubMed 24 Horikoshi Y , Goyagi T , Kudo R et al. The suppressive effects of landiolol administration on the occurrence of postoperative atrial fibrillation and tachycardia, and plasma IL-6 elevation in patients undergoing esophageal surgery: A randomized controlled clinical trial . J Clin Anesth 2017 ; 38 : 111 – 6 . Google Scholar Crossref Search ADS PubMed 25 Chin J H , Moon Y J , Jo J Y et al. Association between postoperatively developed atrial fibrillation and long-term mortality after esophagectomy in esophageal cancer patients: an observational study . PLoS One 2016 ; 11 : e0154931 . Google Scholar Crossref Search ADS PubMed 26 Bobbio A , Caporale D , Internullo E et al. Postoperative outcome of patients undergoing lung resection presenting with new-onset atrial fibrillation managed by amiodarone or diltiazem . Eur J Cardiothorac Surg 2007 ; 31 : 70 – 74 . Google Scholar Crossref Search ADS PubMed © The Author(s) 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/open_access/funder_policies/chorus/standard_publication_model)

Journal

Diseases of the EsophagusOxford University Press

Published: Nov 1, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off