Patients and Methods
Datasets
Inclusion Criteria
Exclusion Criteria
Clinical Staging and Follow-Up
Outcomes Including Definition of Complications
Exposure
Covariates
Statistical Analysis
Results
Comparison of Baseline Patient Demographics and Pretreatment Tumor Stage
Preoperative Patient Demographics
N (%) | No cardiorespiratory comorbidity (N = 982) | Respiratory comorbidity (N = 274) | Cardiac comorbidity (N = 468) | Cardiorespiratory comorbidity (N = 608) | P value* |
---|---|---|---|---|---|
Age (median, IQR), years | 63 (56–70) | 65 (60–71) | 67 (62–72) | 67 (61–71) | < 0.001 |
Sex | 0.001 | ||||
Male | 739 (75.3) | 219 (79.9) | 392 (83.8) | 500 (82.2) | |
Female | 243 (24.8) | 55 (20.1) | 76 (16.2) | 108 (17.8) | |
ASA score | < 0.001 | ||||
1 | 7 (0.7) | 26 (9.5) | 24 (5.1) | 46 (7.6) | |
2 | 345 (35.1) | 160 (58.4) | 270 (57.7) | 356 (58.6) | |
3 | 515 (52.4) | 87 (31.8) | 171 (36.5) | 203 (33.4) | |
4 | 113 (11.5) | 1 (0.4) | 3 (0.6) | 3 (0.5) | |
ECOG score (n = 1264) | 0.094 | ||||
0 | 582 (70.7) | 168 (74.0) | 227 (69.4) | 319 (72.3) | |
1 | 229 (27.8) | 51 (22.5) | 88 (26.9) | 108 (24.5) | |
2 | 12 (1.5) | 7 (3.1) | 11 (3.4) | 13 (3.0) | |
3 | 0 (0) | 1 (0.4) | 1 (0.3) | 1 (0.2) | |
Smoking (n = 850) | 0.086 | ||||
Never | 158 (34.4) | 65 (28.4) | 76 (27.2) | 107 (27.4) | |
Former | 211 (46.0) | 104 (45.4) | 157 (56.3) | 200 (51.2) | |
Currently | 90 (19.6) | 60 (26.2) | 46 (16.5) | 84 (21.5) | |
FVC L, median (IQR) | 4.1 (3.2–4.7) | 3.7 (3.1–4.4) | 3.8 (3.4–4.3) | 3.7 (3.2–4.3) | 0.008 |
FEV1 L, median (IQR) | 2.9 (2.4–3.5) | 2.4 (1.9–3.1) | 2.8 (2.1–3.1) | 2.6 (2.1–3.1) | 0.020 |
FEV1/FVC median % (IQR) (n = 850) | 83.3 (74.3–97.0) | 73.3 (63.2–82.6) | 88.0 (75.9–100) | 84 (71.7–98.0) | 0.747 |
Bicycle test (W) (n = 34) | No observations | 129 (114–156) | 131 (118–157) | 131 (117–160) | |
Left ventricular ejection fraction (%) (n = 234) | 59.5 (55.0–63.0) | 59 (55.0–60.0) | 55 (50.0–60.0) | 56.5 (53.0–60.0) | 0.056 |
cT | 0.127 | ||||
1 | 111 (11.3) | 44 (16.1) | 62 (13.3) | 81 (13.3) | |
2 | 173 (17.6) | 42 (15.3) | 75 (16.0) | 103 (16.9) | |
3 | 614 (62.5) | 168 (61.3) | 308 (65.8) | 392 (64.5) | |
4 | 48 (4.9) | 12 (4.4) | 10 (2.1) | 18 (3.0) | |
X | 36 (3.7) | 8 (2.9) | 13 (2.8) | 14 (2.3) | |
cN | 0.057 | ||||
0 | 438 (44.6) | 125 (45.6) | 182 (38.9) | 244 (40.1) | |
1 | 394 (40.1) | 121 (44.2) | 224 (47.9) | 286 (47.0) | |
2 | 133 (13.5) | 22 (8.0) | 57 (12.2) | 69 (11.4) | |
3 | 17 (1.7) | 6 (2.2) | 5 (1.1) | 9 (1.5) | |
Tumor type | 0.125 | ||||
Adenocarcinoma | 747 (76.1) | 209 (76.3) | 367 (78.2) | 475 (78.1) | |
SCC | 207 (21.1) | 62 (22.6) | 94 (20.1) | 125 (20.6) | |
Other | 28 (2.9) | 3 (1.1) | 7 (1.5) | 8 (1.3) | |
Tumor location | < 0.001 | ||||
Upper/middle | 142 (14.5) | 35 (12.8) | 48 (10.3) | 66 (10.9) | |
Distal | 326 (33.2) | 88 (32.1) | 253 (54.1) | 297 (48.9) | |
EGJ | 514 (52.3) | 151 (55.1) | 167 (35.7) | 245 (40.3) | |
Surgical approach | 0.005 | ||||
Open | 527 (53.7) | 194 (70.8) | 223 (47.7) | 338 (55.6) | |
HMIO | 36 (3.7) | 5 (1.8) | 5 (1.1) | 6 (1.0) | |
TMIO | 419 (42.7) | 75 (27.4) | 240 (51.3) | 264 (43.4) | |
Surgical technique | < 0.001 | ||||
Ivor Lewis | 564 (57.5) | 139 (51.1) | 228 (48.8) | 293 (48.4) | |
McKeown | 305 (31.1) | 62 (22.8) | 140 (30.0) | 179 (29.5) | |
Transhiatal | 112 (11.4) | 71 (26.1) | 99 (21.2) | 134 (22.1) | |
Neoadjuvant treatment | 0.095 | ||||
None | 232 (23.6) | 81 (29.6) | 105 (22.4) | 137 (22.5) | |
Chemotherapy | 182 (18.5) | 54 (19.7) | 54 (11.5) | 90 (14.8) | |
Chemoradiotherapy | 568 (57.8) | 139 (50.7) | 309 (66.0) | 381 (62.7) |
Pretreatment Tumor Characteristics and Surgical Approach
Comparison of Postoperative Outcomes
Respiratory Comorbidity and Postoperative Outcomes
N (%) | No cardiorespiratory comorbidity (N = 982) | Respiratory comorbidity (N = 274) | Cardiac comorbidity (N = 468) | Cardiorespiratory comorbidity (N = 608) | P value* |
---|---|---|---|---|---|
In-hospital mortality | 28 (2.9) | 12 (4.4) | 24 (5.1)** | 26 (4.3) | 0.128 |
Postoperative complication | 632 (64.4) | 194 (70.8)** | 305 (65.2) | 408 (67.1) | 0.263 |
Length of intensive care unit stay, median days (IQR) | 0 (0–2) | 1 (0–5)** | 1 (0–5) | 1 (0–5)** | < 0.001 |
Length of hospital stay, median days (IQR) | 14 (10–22) | 18 (12–30)** | 15 (9–27) | 15 (10–27) | 0.057 |
Reoperation | 48 (7.1) | 20 (10.7) | 47 (11.8)** | 59 (11.4)** | 0.010 |
Pneumonia | 255 (26.0) | 98 (35.8)** | 136 (29.1) | 180 (29.6) | 0.114 |
Anastomotic leak | 111 (11.3) | 42 (15.3) | 73 (15.6)** | 86 (14.1) | 0.095 |
Conduit necrosis | 6 (0.9) | 2 (2.7) | 19 (4.7)** | 19 (3.7)** | 0.001 |
Cardiovascular complication | 174 (17.7) | 57 (20.9) | 129 (27.6)** | 153 (25.2)** | < 0.001 |
Atrial fibrillation | 109 (11.1) | 32 (11.7) | 49 (10.5) | 67 (11.0) | 0.961 |
Respiratory failure | 95 (9.7) | 41 (15.0)** | 66 (14.1)** | 81 (13.3)** | 0.024 |
Pulmonary complication | 343 (34.9) | 122 (44.5)** | 200 (42.7)** | 254 (41.8)** | 0.006 |
Clavien–Dindo score | – | P = 0.037** | P < 0.001** | P < 0.001 | |
Grade I | 216 (28.0) | 64 (26.7) | 75 (26.9) | 105 (22.8) | |
Grade II | 231 (29.9) | 68 (28.3) | 76 (22.2) | 114 (24.7) | |
Grade IIIa | 143 (18.5) | 27 (11.3) | 46 (13.5) | 64 (13.9) | |
Grade IIIb | 56 (7.3) | 22 (9.2) | 19 (5.6) | 30 (6.5) | |
Grade IVa | 93 (12.1) | 45 (18.8) | 84 (24.6) | 100 (21.7) | |
Grade IVb | 25 (3.2) | 13 (5.4) | 26 (7.6) | 32 (6.9) | |
Grade V | 8 (1.0) | 1 (0.42) | 16 (4.7) | 16 (3.5) | |
Clavien–Dindo score, median (IQR) | II (I–IIIa) | II (I–IIIb) | IIIa (II–IVa) | IIIa (II–IVa) | < 0.001 |
Odds ratio (95% CI)a | In-hospital mortality | Postoperative complication | Anastomotic leak | Cardiovascular complication | Atrial fibrillation | Pulmonary complication | Pneumonia | Respiratory failure | Clavien–Dindo grade ≥ IIIa |
---|---|---|---|---|---|---|---|---|---|
Respiratory comorbidityb | 1.36 (0.69–2.67) | 1.21 (0.91–1.63) | 1.64 (1.11–2.41) | 0.88 (0.63–1.23) | 0.74 (0.48–1.13) | 1.26 (0.96–1.66) | 1.39 (1.04–1.85) | 1.43 (0.97–2.09) | 0.95 (0.71–1.27) |
Cardiac comorbidityc | 1.54 (0.88–2.72) | 0.95 (0.75–1.21) | 1.25 (0.90–1.72) | 1.63 (1.25–2.13) | 0.88 (0.60–1.29) | 1.44 (1.14–1.82) | 1.19 (0.92–1.53) | 1.49 (1.06–2.09) | 1.73 (1.34–2.25) |
Cardiac Comorbidity
Cardiorespiratory Comorbidity among Postoperative Complications According to Neoadjuvant Protocol
Odds ratio (95% CI)a | In-hospital mortality | Postoperative complication | Anastomotic leak | Cardiovascular complication | Atrial fibrillation OR (95% CI) | Pulmonary complication | Pneumonia | Respiratory failure | Clavien–Dindo grade ≥ IIIa |
---|---|---|---|---|---|---|---|---|---|
Surgery alone
| |||||||||
Respiratory comorbidity | 1.84 (0.60–5.95) | 0.84 (0.48–1.45) | 1.45 (0.70–2.99) | 0.74 (0.39–1.40) | 0.74 (0.35–1.56) | 1.00 (0.59–1.67) | 1.25 (0.72–2.16) | 0.83 (0.39–1.79) | 0.95 (0.56–1.63) |
Cardiac comorbidity | 0.95 (0.30–2.97) | 1.00 (0.60–1.69) | 0.89 (0.45–1.79) | 1.75 (1.01–3.04) | 1.07 (0.55–2.10) | 1.69 (1.05–2.71) | 1.41 (0.85–2.35) | 1.53 (0.79–2.95) | 1.80 (1.07–3.04) |
Neoadjuvant chemotherapy
| |||||||||
Respiratory comorbidity | 2.03 (0.29–14.40) | 1.60 (0.73–3.37) | 1.46 (0.43–4.94) | 0.90 (0.42–1.90) | 0.84 (0.39–1.84) | 0.96 (0.51–1.81) | 0.91 (0.48–1.74) | 1.87 (0.79–4–43) | 0.90 (0.47–1.75) |
Cardiac comorbidity | 12.62 (1.30–117.80) | 1.49 (0.70–3.15) | 1.51 (0.44–5.10) | 2.00 (1.01–3.96) | 1.55 (0.76–3.18) | 1.57 (0.83–2.98) | 1.62 (0.85–3.08) | 2.35 (0.98–5–65) | 1.96 (0.99–3.88) |
Neoadjuvant chemoradiotherapy
| |||||||||
Respiratory comorbidity | 1.04 (0.38–2.82) | 1.28 (0.85–1.90) | 1.83 (1.11–3.04) | 0.97 (0.61–1.55) | 0.62 (0.29–1.32) | 1.52 (1.04–2.22) | 1.65 (1.10–2.47) | 1.60 (0.94–2.74) | 0.91 (0.60–1.37) |
Cardiac comorbidity | 1.56 (0.75–3.27) | 0.92 (0.68–1.23) | 1.34 (0.90–2.00) | 1.48 (1.04–2.10) | 0.53 (0.27–1.03) | 1.34 (0.99–1.81) | 1.06 (0.75–1.49) | 1.41 (0.89–2.22) | 1.73 (1.23–2.44) |
Preoperative Respiratory and Cardiac Investigations and Postoperative Outcomes
Odds ratio (95% CI) | In-hospital mortality | Postoperative complication | Anastomotic leak | Cardiovascular complication | Atrial fibrillation | Pulmonary complication | Pneumonia | Respiratory failure | Clavien–Dindo grade ≥ IIIa |
---|---|---|---|---|---|---|---|---|---|
All patients unadjusted
| |||||||||
FEV1/FVC ratio | |||||||||
≤ 70.0% (ref) | – | – | – | – | – | – | – | – | – |
> 70.0% LVEF | 0.91 (0.30–2.75) | 0.44 (0.29–0.66) | 1.28 (0.69–2.38) | 0.57 (0.39–0.84) | 0.22 (0.14–0.34) | 0.61(0.43–0.86) | 0.48 (0.33–0.70) | 0.59 (0.35–1.01) | 1.41 (0.95–2.08) |
≤ 55.0% (ref) | – | – | – | – | – | – | – | – | – |
> 55.0% | 0.96 (0.21–4.39) | 0.58 (0.31–1.09) | 0.33 (0.12–0.91) | 0.98 (0.56–1.72) | 1.04 (0.59–1.85) | 0.95 (0.56–1.59) | 0.91 (0.53–1.56) | 0.54 (0.24–1.20) | 0.90 (0.50–1.62) |
All patients adjusted
a
| |||||||||
FEV1/FVC ratio | |||||||||
≤ 70.0% (ref) | – | – | – | – | – | – | – | – | – |
> 70.0% LVEF | 1.13 (0.34–3.73) | 0.57 (0.37–0.89) | 0.79 (0.40–1.56) | 0.73 (0.48–1.11) | 0.46 (0.28–0.75) | 0.76 (0.52–1.11) | 0.72 (0.48–1.07) | 0.76 (0.43–1.34) | 1.24 (0.82–1.89) |
≤ 55.0% (ref) | – | – | – | – | – | – | – | – | – |
> 55.0% | 0.74 (0.15–3.71) | 0.55 (0.28–1.07) | 0.34 (0.12–0.95) | 1.04 (0.57–1.89) | 1.11 (0.61–2.03) | 0.97 (0.57–1.65) | 0.91 (0.52–1.60) | 0.56 (0.24–1.28) | 0.94 (0.51–1.72) |