Original article

Impact of postoperative morbidity on long-term survival after oesophagectomy

M. W. Hii1,2 , B. M. Smithers1,2,3 , D. C. Gotley1,2,3 , J. M. Thomas1,3 , I. Thomson1,2 , I. Martin1 and A. P. Barbour1,2
Department of Upper Gastrointestinal and Soft Tissue Tumour Surgery and 2 Department of Surgery, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, and 3 Mater Medical Research Institute, South Brisbane, Queensland, Australia Correspondence to: Dr M. W. Hii, Upper Gastrointestinal and Soft Tissue Unit, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, Queensland 4102, Australia (e-mail: mickhii@gmail.com)
1

Background: Oesophageal malignancy is a disease with a poor prognosis. Oesophagectomy is the

mainstay of curative treatment but associated with substantial morbidity and mortality. Although mortality rates have improved, the incidence of perioperative morbidity remains high. This study assessed the impact of postoperative morbidity on long-term outcomes. Methods: A prospective database was designed for patients undergoing oesophagectomy for malignancy from 1998 to 2011. An observational cohort study was performed with these data, assessing intraoperative technical complications, postoperative morbidity and effects on overall survival. Results: Some 618 patients were included, with a median follow-up of 51 months for survivors. The overall complication rate was 646 per cent (399 of 618), with technical complications in 124 patients (201 per cent) and medical complications in 339 (549 per cent). Technical complications were associated with longer duration of surgery (308 min versus 293 min in those with no technical complications; P = 0017), greater operative blood loss (448 versus 389 ml respectively; P = 0035) and longer length of stay (22 versus 13 days; P < 0001). Medical complications were associated with greater intraoperative blood loss (418 ml versus 380 ml in those with no medical complications; P = 0013) and greater length of stay (16 versus 12 days respectively; P < 0001). Median overall and disease-free survival were 41 and 43 months. After controlling for age, tumour stage, resection margin, length of tumour, adjuvant therapy, procedure type and co-morbidities, there was no effect of postoperative complications on disease-specic survival. Conclusion: Technical and medical complications following oesophagectomy were associated with greater intraoperative blood loss and a longer duration of inpatient stay, but did not predict diseasespecic survival.
Presented to the Fourth Asia-Pacic Gastroesophageal Cancer Congress, Singapore, July 2012 Paper accepted 13 September 2012 Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.8973

Introduction

Oesophageal resection for malignant disease is associated with high rates of morbidity and mortality, especially in low-volume centres of care1 . Although mortality rates have fallen2,3 , morbidity rates are still high. Contemporary large series report overall morbidity rates of 26667 per cent, with major morbidity in 2636 per cent of patients undergoing surgery4 9 . Improvements in perioperative mortality have been attributed to better patient selection, modern anaesthesia, intensive care and postoperative support, perioperative
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nutrition and treatment in high-volume centres1,3,10 . Lifethreatening complications may be better managed. Surgical techniques have also altered over time, with a trend towards more extensive nodal dissection and the introduction of minimally invasive oesophagectomy4,6,7,11,12 . There is little evidence that any of these aspects of management has lowered complication rates. It is important to understand the impact of postoperative complications on longterm patient outcomes, to see whether measures that might reduce complication rates are likely to impact on survival.
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Morbidity arising from oesophagectomy is generally considered to be technical or medical13 16 . Technical complications relate to intraoperative events that damage structures or result in inadequate reconstruction13 16 . Medical complications are typically pulmonary, cardiac or infective, and arise, in part, from the systemic insult of the surgery itself13,14,16 . There is conicting evidence regarding the effects of perioperative complications on long-term survival after oesophagectomy13 18 . There is weak evidence for other cancer operations, in particular hepatic and colorectal surgery, that links postoperative complications with poorer survival19 21 . Although there is no direct evidence, it has been suggested that the inammatory and immune modulatory effects of surgery and surgical morbidity have a negative effect on the host response to malignant disease18 21 . This study was undertaken to dene the incidence of complications in a large series of patients undergoing oesophagectomy for cancer, and to assess the effect of complications on long-term survival.
Methods

A prospective database (Microsoft Access version 1.0 1992; Microsoft, Washington, DC, USA) has been maintained of all patients with oesophageal carcinoma under the care of surgeons in the Department of Upper Gastrointestinal and Soft Tissue Tumour Surgery of the Princess Alexandra Hospital (PAH). Permission to collect and use the information was approved by the hospital ethics committee (PAH HREC/03/QPAH/165). Patient details were recorded at presentation, during all treatments, and at follow-up visits until patient death, or to October 2011 for those patients still alive. Clinicians and a research nurse, whose primary responsibility was data collection, completed all records. Patients who had a resection for squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction between January 1998 and June 2011 were included. Preoperative morbidity was dened by the following criteria. Cardiac disease included the requirement for pharmaceutical or mechanical intervention (percutaneous stent insertion, coronary artery bypass grafting or pacemaker) for cardiac ischaemia or arrhythmia. Respiratory disease was dened as the use of any long-term medication to treat a specic pulmonary disorder. Renal disease was dened as a baseline creatinine level above 90 mol/l. Diabetes was dened as the use of oral hypoglycaemic medication or insulin. The severity of co-morbidities was not recorded.
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Anaesthetic tness was graded according to the American Society of Anesthesiologists classication22,23 . Preoperative staging included endoscopy and computed tomography (CT) of the chest, abdomen and pelvis, and, from 2004, uorodeoxyglucosepositron emission tomography. Endoscopic ultrasonography was used selectively. Treatment was directed by local protocols. Patients with early tumours or those medically unsuitable for neoadjuvant therapy proceeded directly to surgery. Patients receiving preoperative chemoradiation had a radiotherapy dose varying from 35 to 45 Gy according to trial or institutional protocols24 . Preoperative chemotherapy consisted of the combination of cisplatin and infusional 5-uorouracil (5-FU) (2 cycles), or preoperative and postoperative epirubicin, cisplatin and 5-FU25 . Pathological stage was determined according to the International Union Against Cancer (UICC) staging system (7th edition)26 . Completeness of resection was classied as R0 for negative margins, R1 for microscopically positive margins (involved or within 1 mm) and R2 for macroscopically positive margins. Postoperative morbidity was grouped as technical or medical to maintain consistency with previous reports, but not stratied by severity13,14,16 . Technical complications were classied as damage to surrounding structures (chyle leak, recurrent laryngeal nerve palsy, postoperative haemorrhage, tracheooesophageal stula) or inadequate reconstruction (anastomotic leak, conduit necrosis). Chyle leak was dened as excessive drain output (more than 500 ml in 24 h), persistent for more than 2 days and conrmed by triglyceride analysis. Recurrent laryngeal nerve palsy was conrmed by laryngoscopy in patients with altered phonation or aspiration pneumonia. Postoperative haemorrhage was dened as the requirement for blood transfusion within 24 h of surgery, or reoperation for bleeding. Anastomotic leak was dened as any evidence of leak, as shown clinically by the loss of gastrointestinal contents into a drain or as seen on contrast swallow routinely performed on postoperative day 6 or 7. Patients with an anastomotic leak were analysed as a single group. Conduit necrosis was diagnosed at endoscopy or surgery. Fistula from airway to conduit or oesophagus was conrmed by endoscopy and bronchoscopy. Postoperative medical complications were grouped into respiratory, cardiac, wound infection, urinary, gastroparesis, delirium and thromboembolic complications. Pulmonary complications included respiratory failure, pneumonia and acute respiratory distress syndrome. Respiratory failure was dened as prolongation of intubation or as
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reintubation to allow facilitation of oxygenation. Pneumonia was dened as a febrile illness with consistent clinical ndings and consolidation on radiological imaging. Acute respiratory distress syndrome was dened as a non-infective respiratory decompensation with consistent radiological ndings. Cardiac complications included arrhythmias, dened as abnormalities or changes from the preoperative electrocardiogram, and myocardial ischaemia, dened as increased cardiac enzyme levels with a characteristic clinical picture. Wound infection was dened as persistent erythema around a surgical wound or as purulent discharge from a wound requiring antibiotic therapy and/or drainage. Urinary complications included acute urinary retention requiring recatheterization and urosepsis conrmed by urine culture. Postoperative gastroparesis was dened as poor emptying of the gastric conduit for more than 5 days and after the return of normal bowel function requiring nasogastric tube decompression. Delirium was dened as disorientation and altered mental state that persisted for more than 24 h. Thromboembolic complications included deep vein thrombosis or pulmonary embolism conrmed by venous ultrasonography, ventilation/perfusion scan or high-resolution CT pulmonary angiography. Data allowing stratication of the severity of complications were not recorded. A separate analysis for patients who had a reoperation for technical complications was performed. Procedure-related mortality was dened as any death within 90 days of surgery, or as death before discharge from hospital. Various combinations of open and minimally invasive surgery were used and have been reported elsewhere4,11 . These included: open transthoracic oesophagogastrectomy; thoracoscopically assisted three-eld oesophagectomy with the abdominal procedure performed via a laparotomy; thoracoscopic and laparoscopic oesophagectomy; and an open three-eld resection (McKeown). All patients in the latter three groups had a cervical anastomosis. A jejunostomy was constructed in all patients, and feeding commenced on the rst postoperative day. Standard dissection included removal of the nodal stations from the subcarinal, posterior mediastinal, paraoesophageal, diaphragmatic, right and left paracardial, left gastric artery, coeliac axis, suprapancreatic region and common hepatic regions. These correspond to the following lymph node stations in accordance with the Japanese Research Society for Gastric Cancer27 : 1, 2, 3, 4Sb, 7, 11p, 11d, 12a, 110, 111 and 112. The superior mediastinal, recurrent laryngeal and cervical nodes were not removed, nor was the thoracic duct.
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After discharge, all patients visited outpatients every 3 months for 2 years, every 6 months for 4 years, and once a year thereafter. Survival was calculated from the date of operation, with the analysis including postoperative deaths.

Statistical analysis
The analysis of results was performed with the entire group as well as separate analyses for the surgery-alone and neoadjuvant groups. To identify the clinicopathological factors associated with outcome, univariable analyses were undertaken for disease-specic and overall survival, separately for the surgery-alone and neoadjuvant therapy groups. Patients with stage IV disease were excluded from these analyses. Continuous variables were expressed as median (range) and compared using the MannWhitney U test. Comparison of categorical variables was done by contingency table analysis using 2 tests. Comparison of means was based on Students t test. Survival data were summarized using the KaplanMeier method. Unadjusted comparisons of survival times were based on the log rank test. Factors found signicant after univariable analysis were included in multivariable analyses. Multivariable analyses of survival times were based on Cox regression. Predictors of complications were assessed by logistic regression. For all calculations, P < 0050 was considered signicant. Data analysis was performed using SPSS version 20 (IBM, Armonk, New York, USA).
Results

A total of 618 patients were included in this series. Median follow-up for survivors was 51 (range 2151) months. Perioperative morbidity and survival data were available for all patients. Patient characteristics are summarized in Tables 1 and 2. Patients in the neoadjuvant therapy group had more tumours larger than 6 cm and a higher UICC stage. Patients in the surgery-alone group were older than those in the neoadjuvant therapy group (66 (2784) versus 62 (1679) years respectively; P < 0001) and had a higher incidence of medical co-morbidities. There was no difference in median operative blood loss between the surgery-alone group and the neoadjuvant therapy group (350 (02000) versus 350 (02300) ml respectively; P = 0605), or in median operating time (290 (150503) versus 285 (165540) min; P = 0495). The overall median length of stay (LOS) was 14 (7123) days. There was no difference between the surgery-alone and neoadjuvant therapy groups (median 14 (7123) versus 13 (797) days respectively; P = 0784).
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Table 1

Patient characteristics
Entire group (n = 618) Surgery alone (n = 316) 264 : 52 12 (38) 213 (674) 88 (278) 2 (06) 1 (03) 99 (313) 94 (297) 31 (98) 39 (123) 212 (671) 74 (234) 18 (57) 12 (38) 265 (839) 50 (158) 1 (03) 260 (823) 29 (92) 27 (85) 1 (03) 22 (70) 224 (709) 69 (218) 41 (130) 83 (263) 73 (231) 114 (361) 5 (16) 272 (861) 5 (16) 4 (13) Adjuvant therapy (n = 302) 259 : 43 9 (30) 217 (719) 75 (248) 1 (03) 0 (0) 51 (169) 38 (126) 23 (76) 14 (46) 224 (742) 63 (209) 10 (33) 5 (17) 0208 507 (820) 110 (178) 1 (02) 493 (798) 87 (141) 38 (61) 1 (02) 54 (87) 433 (701) 130 (210) 77 (125) 110 (178) 188 (304) 236 (382) 7 (11) 547 (885) 7 (11) 6 (10) 242 (801) 60 (199) 0 (0) 0001 233 (772) 58 (192) 11 (36) 0315 0 (0) 32 (106) 209 (692) 61 (202) < 0001 36 (119) 27 (89) 115 (381) 122 (404) 2 (07) 275 (911) 2 (07) 2 (07) < 0001 < 0001 0393 0001 0108

P* 0502 0668

Sex ratio (M : F) ASA grade I II III IV Missing Co-morbidities Cardiac Respiratory Diabetes Renal Type of oesophagectomy Thoracoscopically assisted Transthoracic Minimally invasive Other Histology Adenocarcinoma Squamous cell carcinoma Missing Tumour length (cm) 6 >6 Missing Tumour location Proximal third Middle third Distal third Oesophagogastric junction UICC stage 0 I II III IV R0 resection In-hospital mortality 90-day mortality

523 : 95 21 (34) 430 (696) 163 (264) 3 (05) 1 (02) 150 (243) 132 (214) 54 (87) 53 (86) 436 (706) 137 (222) 28 (45) 17 (28)

0059 0451 0686

Values in parentheses are percentages. ASA, American Society of Anesthesiologists; UICC, International Union Against Cancer. *2 test.

The incidence of postoperative complications is shown in Table 3. Overall, complications occurred in 646 per cent of patients. The only signicant difference between the two treatment groups was in the incidence of urinary complications, which were more frequent in patients treated by surgery alone (P = 0037). Technical complications were associated with longer median operating time (308 (range 165510) versus 293 (150540) min; P = 0017) and greater median intraoperative blood loss (448 (502300) versus 389 (502000) ml; P = 0035) than in patients with no technical complications. Technical complications were not associated with patient age, ASA grade, UICC stage, tumour location,
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neoadjuvant therapy, procedure type or pre-existing comorbidities (Table S1, supporting information). Medical complications were not associated with longer median operating time (294 (175540) versus 299 (150503) min; P = 0113), but were associated with greater intraoperative blood loss (417 (02000) versus 380 (02300) ml; P = 0013) and longer length of stay (16 (8123) versus 12 (768) days; P < 0001). Of the 123 patients with UICC stage 0III disease who had a technical complication, 67 (545 per cent) also experienced a medical compliation. This was similar to the rate of medical complications in patients without technical complications (269 of 488, 551 per cent; P = 0919).
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Table 2

Patient characteristics according to type of oesophagectomy

Thoracoscopically assisted (n = 436) Transthoracic (n = 137) 122 : 15 1 (07) 95 (693) 38 (277) 2 (15) 1 (07) 32 (234) 31 (226) 9 (66) 11 (80) 127 (927) 10 (73) 0 (0) 93 (679) 0 (0) 1 (07) 67 (489) 69 (504) 9 (66) 13 (95) 41 (299) 73 (533) 1 (07) 116 (847) 0 (0) 0 (0) Minimally invasive (n = 28) 24 : 4 4 (14) 18 (64) 6 (21) 0 (0) 0 (0) 11 (39) 10 (36) 2 (7) 4 (14) 24 (86) 4 (14) 0 (0) 25 (89) 0 (0) 2 (7) 22 (79) 4 (14) < 0001 60 (138) 90 (206) 137 (314) 143 (328) 6 (14) 395 (906) 6 (14) 5 (11) 8 (29) 3 (11) 6 (21) 11 (39) 0 (0) 23 (82) 1 (4) 1 (4) 0142 0077 0613 0528 0001

P* 0282 0010

Sex ratio (M : F) ASA grade I II III IV Missing Co-morbidities Cardiac Respiratory Diabetes Renal Histology Adenocarcinoma Squamous cell carcinoma Missing Tumour length < 6 cm Tumour location Proximal third Middle third Distal third Oesophagogastric junction UICC stage 0 I II III IV R0 In-hospital mortality 90-day mortality

364 : 72 15 (34) 307 (704) 113 (259) 1 (02) 0 (0) 100 (229) 82 (188) 40 (92) 36 (83) 344 (789) 91 (209) 1 (02) 362 (830) 1 (02) 50 (115) 336 (771) 49 (112)

0006 < 0001

0081 0203 0187

Values in parentheses are percentages. ASA, American Society of Anesthesiologists; UICC, International Union Against Cancer. *2 test.
Table 3

Postoperative morbidity
Entire group (n = 618) Surgery alone (n = 316) 203 (642) 60 (190) 36 (114) 16 (51) 6 (19) 4 (13) 3 (09) 2 (06) 178 (563) 123 (389) 44 (139) 32 (101) 6 (19) 10 (32) 18 (57) 4 (13) 18 (57) 87 (275) 20 (63) Neoadjuvant therapy (n = 302) 196 (649) 64 (212) 33 (109) 23 (76) 7 (23) 5 (17) 5 (17) 3 (10) 161 (533) 107 (354) 47 (156) 28 (93) 2 (07) 2 (07) 13 (43) 7 (23) 12 (40) 67 (222) 20 (66)

P* 0867 0547 0899 0247 0784 0747 0496 0680 0468 0405 0572 0786 0287 0037 0465 0374 0353 0137 1000

Total complications Technical complications Anastomotic leak Chyle leak Haemorrhage Necrotic conduit Vocal cord palsy Tracheo-oesophageal stula Medical complications Respiratory Cardiac Infection Gastroparesis Urinary Delirium Thromboembolic Other complications Multiple complications Reoperation for technical complication

399 (646) 124 (201) 69 (112) 39 (63) 13 (21) 9 (15) 8 (13) 5 (08) 339 (549) 230 (372) 91 (147) 60 (97) 8 (13) 12 (19) 31 (50) 11 (18) 30 (49) 154 (249) 40 (65)

Values in parentheses are percentages. *2 test.

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Table 4

Univariable and multivariable analysis of overall and disease-free survival in the surgery-alone group (excluding patients with stage 4 cancer)
Overall survival Length (months) Univariable P* 0001 0601 260 51 260 50 1 257 27 27 41 83 73 114 271 40 201 110 60 251 36 275 16 295 6 305 4 307 3 308 2 309 177 134 122 189 44 267 32 279 6 305 10 301 18 293 4 307 17 294 87 224 20 251 48 39 0644 48 31 0002 52 24 < 0001 NA NA 34 17 < 0001 57 15 36 74 24 53 22 52 47 44 14 47 15 48 NA 47 10 47 36 57 47 47 30 52 24 48 21 47 NA 47 36 48 11 47 53 44 30 57 24 53 0011 0011 0016 0530 0307 0023 NA 0046 0198 0640 0041 0186 0624 NA 0138 0879 0476 0013 0217 0420 0040 16 (10, 25) 1 0 0026 52 (12, 222) 1 0 0413 < 0001 0050 < 0001 < 0001 0002 0535 0982 0516 0520 58 24 < 0001 NA NA 39 18 < 0001 79 15 47 NA 27 65 22 65 47 53 27 53 24 53 NA 53 10 53 48 65 53 52 35 58 24 57 21 53 NA 53 36 53 11 53 NA 52 35 67 26 65 0048 0012 0012 0467 0585 0068 0647 0028 0453 0990 0223 0090 0954 0404 0431 0716 0315 0059 0283 0077 0051 < 0001 0105 < 0001 < 0001 0007 0443 0987 0251 53 47 0002 0445 Multivariable P 0006 Hazard ratio 10 (10, 10) 57 47 0808 Length (months) Disease-free survival Univariable P* 0120 0506 Multivariable P Hazard ratio

n Age (years) Sex M F Histology Adenocarcinoma Squamous cell carcinoma Missing Tumour length (cm) 6 >6 Missing UICC stage 0 I II III Resection margin R0 R12 Complications Any complication No complication Technical complications No technical complication Anastomotic leak No anastomotic leak Chyle leak No chyle leak Haemorrhage No haemorrhage Necrotic conduit No necrotic conduit Vocal cord palsy No vocal cord palsy Tracheo-oesophageal stula No tracheo-oesophageal stula Medical complications No medical complication Respiratory No respiratory complication Cardiac No cardiac complication Infection No infection Gastroparesis No gastroparesis Urinary No urinary complication Delirium No delirium Thromboembolic No thromboembolic complication Other complication No other complication Multiple complications None or single complication Reoperation for technical complication No technical complication

10 34 (10, 115) 118 (36, 383) 204 (64, 656) 10 20 (13, 30)

10 35 (08, 157) 163 (39, 678) 314 (76, 1293) 10 18 (12, 28)

Values in parentheses are 95 per cent condence intervals. UICC, International Union Against Cancer; NA, data not available. *Log rank test, except MannWhitney U test; Cox regression analysis.

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Table 5

Univariable and multivariable analysis of overall and disease-free survival in the neoadjuvant therapy group (excluding patients with stage 4 cancer)
Overall survival Length (months) Univariable P* 0292 0646 257 43 240 60 231 58 11 36 27 115 122 275 25 194 106 63 237 32 268 23 277 7 293 5 295 5 295 3 297 159 141 106 194 46 254 28 272 2 298 2 298 13 287 7 293 12 288 66 234 20 237 40 47 0814 37 55 0049 47 27 < 0001 NA NA 40 27 0036 44 17 41 38 40 41 41 41 27 41 40 41 NA 38 25 41 25 41 44 38 41 41 34 43 72 38 NA 41 NA 40 53 41 32 41 44 40 44 40 44 41 0631 0938 0818 0664 0481 NA 0551 0630 0462 0910 0425 0518 NA NA 0475 0905 0616 0756 0469 0133 41 27 < 0001 NA NA 49 24 0021 37 17 36 35 30 36 32 36 25 36 NA 35 NA 35 25 36 25 36 41 33 31 36 37 35 72 35 NA 35 NA 35 NA 35 NA 35 44 35 41 35 40 36 0546 0447 0674 0336 0472 0086 0628 0707 0101 0826 0614 0297 0515 0174 0236 0474 0990 0261 0763 34 55 0091 34 61 0172 Multivariable P Hazard ratio Length (months) Disease-free survival Univariable P* 0844 0294 Multivariable P Hazard ratio

n Age (years) Sex M F Histology Adenocarcinoma Squamous cell carcinoma Tumour length (cm) 6 >6 Missing UICC stage 0 I II III Resection margin R0 R1/2 Complications Any complication No complication Technical complications No technical complication Anastomotic leak No anastomotic leak Chyle leak No chyle leak Haemorrhage No haemorrhage Necrotic conduit No necrotic conduit Vocal cord palsy No vocal cord palsy Tracheo-oesophageal stula No tracheo-oesophageal stula Medical complications No medical complications Respiratory No respiratory complication Cardiac No cardiac complication Infection No infection Gastroparesis No gastroparesis Urinary No urinary complication Delirium No delirium Thromboembolic No thromboembolic complication Other complication No other complication Multiple complications None or single complication Reoperation for technical complication No technical complication

< 0001 < 0001 < 0001 0003 0362

10 53 (25, 115) 65 (26, 161) 17 (12, 23)

< 0001 < 0001 < 0001 0003 0226

10 175 (43, 714) 50 (22, 116) 17 (12, 24)

Values in parentheses are 95 per cent condence intervals. UICC, International Union Against Cancer; NA, data not available. *Log rank test, except MannWhitney U test; Cox regression analysis.

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Specically relating to pulmonary complications, there were 51 (414 per cent) of 123 in the technical complication group, compared with 177 (363 per cent) of 488 in the group without technical complications (P = 0298). No other subtype of medical complication was associated with technical complications (Table S2, supporting information). Patients with no complications had a median LOS of 12 (range 725) days, compared with 16 (8123) days for those with complications (P < 0001). In patients without a technical complication, median LOS was 13 (7123) days versus 22 (897) days when a technical complication occurred (P < 0001). The in-hospital mortality rate was 11 per cent and the 90-day mortality rate was 10 per cent. In-hospital death occurred in six (15 per cent) of 399 patients after any complication and in one (05 per cent) of 219 patients with no complication (P = 0431). In-hospital mortality occurred in two (16 per cent) of 124 patients with technical complications and in ve (10 per cent) of 494 patients without (P = 0632). Median (range) overall and disease-specic survival times were 41 (2151) and 43 (1151) months respectively. In the surgery-alone group, multivariable analysis using the signicant univariable factors found that age, cardiac complications, R1/2 resection and UICC stage were independent prognostic factors for overall survival (Table 4). In terms of technical complications, postoperative tracheo-oesophageal stula was a predictor of poor overall but not disease-free survival. No other postoperative surgical complications were signicant prognostic factors. For disease-free survival, UICC stage and R1/2 resection were the only signicant prognostic factors (Table 4). For the neoadjuvant group, multivariable analysis revealed UICC stage to be the only independent prognostic factor for both overall and disease-free survival (Table 5). Technical complications, individual complications and complication groups were not associated with disease-free survival. After stratication by procedure type (thoracoscopically assisted oesophagectomy, transthoracic oesophagectomy, minimally invasive oesophagectomy), multivariable analysis of postoperative morbidity did not reveal any prognostic factors for overall or disease-free survival (Table S3, supporting information). Technical complications requiring reoperation also failed to be a prognostic factor for overall or disease-free survival for the surgery-alone or neoadjuvant therapy group (Tables 4 and 5).
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Discussion

The incidence of postoperative morbidity was similar to that seen in other large series13 18 . Technical complications were seen in 201 per cent and medical complications in 549 per cent of the cohort. There was no difference in the rate of technical complications in patients having neoadjuvant therapy compared with those progressing directly to surgery. Although this nding is subject to selection bias, it is similar to that found in other series13,14 . Patients in the surgery-alone group were signicantly older and had a higher incidence of medical co-morbidities, but neither age nor co-morbidities were independent predictors of postoperative or technical complications. Technical complications were associated with surrogate markers of difcult surgery, with longer operating times and greater intraoperative blood loss. As shown by others13,14,16 , technical complications were associated with prolonged LOS. It may be expected that a higher incidence of medical complications would follow technical complications, and, although other studies have supported this14,16 , the present study did not. Technical complications overall had no effect on overall or disease-free survival rates in patients with oesophageal cancer. Only two patients in the surgery-alone group developed tracheo-oesophageal stulas, so this specic complication became a predictor of poor overall survival. It is difcult to draw conclusions, except to comment that this problem is a substantial physiological challenge requiring further operative intervention. The outcomes from this study and three other reports13,14,17 , including data from more than 1600 patients, suggest that technical complications are not associated with poorer overall survival. In contrast, two large series have described a link between technical complications and worse survival16,18 . One of these was a population-based prospective study in which almost half of the patients had surgery at low-volume (9 or fewer patients per year) institutions18 . This introduces variations in selection criteria for surgery, and in the diagnosis and management of postoperative morbidity. These differences can affect perioperative mortality adversely and, although patients who died in the perioperative period were excluded from analysis, there may be a persisting impact on longterm survival18 . The patient group in the other series16 was similar to that in the present study. As neither patient selection nor complication severity was stratied objectively, these factors may be important predictors of the ability to tolerate the impact of complications after surgery.
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In terms of medical morbidity, cardiac complications were predictive of poorer overall but not disease-free survival in the surgery-alone group. Wherever possible, steps should be taken to minimize the risk and/or severity of perioperative cardiac complications. Otherwise, the data failed to show an effect for any other medical complication on overall or disease-free survival. A signicant shortcoming of this database was the lack of objective stratication of complication severity. The Accordion28 and Clavien29 severity grading systems have become widely used in recent years. It is possible that a relationship exists between more severe morbidity and survival that could be identied through such grading systems. Using reoperation as a surrogate for complication severity in the present series did not, however, show any predictive value for overall or disease-free survival. Despite the size of this study, the incidence of several complications (for example tracheo-oesophageal stula) was low, so for some specic complications this database may not have sufcient power for analysis. Despite the lack of an effect on disease-free survival following technical complications, reducing their incidence should remain an important target for improvement1 . The impact of complications on other long-term measures, such as quality of life, may be considerable and merits further attention. In addition, agreed clear denitions of the complications specically related to oesophagectomy will allow better comparison between studies.

Disclosure

The authors declare no conict of interest.

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Supporting information

Additional supporting information may be found in the online version of this article: Table S1 Identication of variables predictive of technical complications (Word document) Table S2 Incidence of medical complications in patients with and without technical complications (Word document) Table S3 Multivariable analysis for predictors of survival by procedure type (Word document)

2012 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd

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British Journal of Surgery 2013; 100: 95104