Rates of Anastomotic Complications and their Management following

Esophagectomy: Results of the Oesophago-Gastric Anastomosis Audit

(OGAA)

Oesophago-Gastric Anastomosis Study Group on behalf of the West Midlands

Research Collaborative

*Collaborating authors are listed in appendix 1

Corresponding Author:

Mr. Ewen A Griffiths,

Consultant Upper GI Surgeon,

Department of Upper Gastrointestinal Surgery,

Area 6, 7th Floor, Queen Elizabeth Hospital Birmingham,

Mindelsohn Way, Edgbaston, Birmingham

B15 2WB

Email: [email protected]

Telephone: 0121 3715886

Fax: 0121 371 5896

Category: Original research

Running title: Anastomotic complications and management after esophagectomy

Abstract word count: 248

Main body word count: 3,258

Number of tables: 4
Number of supplementary tables: 2

Number of figures: 3

Keywords: esophagectomy; anastomotic leak; outcomes; esophageal cancer

Acknowledgements: We are grateful to the Birmingham Surgical Trials Consortium

at the University of Birmingham for the use of their servers for secure online data

collection.

Competing interests: The authors have no competing interests to declare

Abstract

Objective

This study aimed to characterize the global variation in rates and management of

anastomotic leak (AL) and conduit necrosis (CN) after esophagectomy. The study

evaluated techniques to achieve successful AL/CN management.

Background

The outcomes after anastomotic complications is currently uncertain. Optimum

strategies to manage AL/CN are unknown and have not been assessed in an

international cohort.

Method

This prospective multicenter cohort study included patients undergoing

esophagectomy for esophageal cancer between April 2018 and Dec 2018 (with 90

days of follow-up). Primary outcome was AL and CN defined by the Esophageal

Complications Consensus Group. Secondary outcome was successful rates of AL/CN

management. Management success was defined as patients being alive at 90 day

post-operatively and requiring no further AL/CN treatment.

Results

This study included 2247 esophagectomies across 137 hospitals in 41 countries. The

AL rate was 14.2% (n=319) and CN rate was 2.7% (n=60). The 90-day mortality for

patients with AL was 11.3%. Of the 329 patients with AL/CN, the primary management

was successful in 69.6% of cases. Subsequent rounds of management lead to an

increase in the rate of successful treatment, with cumulative success rates of 85.4%
and 88.1% after secondary and tertiary management, respectively. Increasing

severity of AL was associated with a significantly higher 90-day mortality rate (Type 1-

3.2% vs. Type 2- 13.2% vs. Type 3- 24.7%, p<0.001).

Conclusion

Patient outcomes worsen significantly with increasing AL and CN Type. Re-

intervention after failed leak management can be successful and should not deter

surgeons trying alternative leak management strategies.

Introduction

Esophagectomy remains the mainstay of curative treatment for esophageal cancers.

Current clinical practice and postoperative outcomes vary between international

centers 1–3. Anastomotic leak rates vary from 8% - 20% following esophagectomy and

are associated with high perioperative morbidity and mortality1,4–7. Pre-operative

patient factors, neoadjuvant treatments, technical factors (e.g. adoption of minimally

invasive techniques8,9), and hospital factors10,11 have been suggested to impact

anastomotic leaks.2,12

Owing to previous variations in the definitions of anastomotic complications, the

Esophageal Complications Consensus Group (ECCG) proposed standardization of

reporting outcomes framework to facilitate international comparison of outcomes

across differing studies7. Subsequent benchmarking studies have provided the

standard to which post-operative complication rates can be compared, however they

have not reported outcomes of the individual types of anastomotic leak or conduit

necrosis7,13,14. In addition, treatment strategies to manage anastomotic complications

have not be assessed in an international cohort study. This is important as some

patients require multiple treatments for these complications and the flow of patients

via the pathways of primary, secondary and tertiary treatment strategies has not yet

been reported.

The Oesophago-Gastric Anastomosis Audit (OGAA) is an international multi-center

prospective study to audit outcomes, specifically anastomotic complications, globally,

following esophagectomy for esophageal cancers. The primary aim and outcome of

the study was to report on the incidence of anastomotic leaks and conduit necrosis
after esophagectomy. Secondary aims were to examine the flow of treatment

modalities (primary, secondary and tertiary treatments strategies) for anastomotic

complications and to analyze the predictors associated with successful primary

treatment.

Methods

Study Design and Setting

Any center performing elective esophagectomy for esophageal cancer was invited to

contribute to this study. There was no minimum unit volume to register for the study

and participation was voluntary. The protocol for this study has been published

previously15. The research collaborative model has also been described previously,

successfully delivering a number of international and national cohort studies16–

19
. Participating hospitals were not required to amend or standardize surgical or

management pathways, and no changes were made to individual patients’ care as

part of this observational study. Teams of surgeons, surgical trainees, research nurses

or medical students prospectively identified eligible patients over a nine month period

from 2nd April 2018 to 31st December 2018, with 90 day follow-up until 5th April 2019.

Data collection teams at each hospital were supervised by an attending or consultant

surgeon, who took overall responsibility for local data quality and case ascertainment.

Inclusion and Exclusion Criteria

All consecutive adult patients having elective (planned) esophagectomy for

malignancy were included. All surgical approaches (two-stage, three-stage,

thoracoabdominal, or transhiatal) using any combination of open, robotic or standard

minimal access approaches were included, as were thoracic and cervical anastomotic
locations. Exclusion criteria were: (i) extended total gastrectomy; (ii)

pharyngolaryngoesophagectomy; (iii) colonic interposition and small bowel jejunal

interposition reconstructions; and (iv) emergency or benign resections. Patients were

followed up for 90 days after the date of surgical resection. 

Outcome Measures

The primary outcome was anastomotic leaks and conduit necrosis as defined by the

ECCG framework7 . Anastomotic leak was defined as a full thickness GI defect

involving oesophagus, anastomosis, staple line, or conduit irrespective of

presentation or method of identification. These were further categorised as follows:

• Type I: Local defect requiring no change in therapy or treated medically or

with dietary modification.

• Type II: Localized defect requiring interventional but not surgical therapy, for

example, interventional radiology drain, stent or bedside opening, and packing

of incision

• Type III: Localized defect requiring surgical therapy.

Conduit necrosis was defined as post-operative identification of necrosis or

ischaemia affecting the gastric conduit, and was further categorised as:

• Type I: Focal necrosis identified endoscopically requiring additional monitoring

or non-surgical therapy

• Type II: Focal necrosis identified endoscopically, and not associated with free

anastomotic or conduit leak, which required surgical therapy not involving

esophageal diversion
 • Type III: Extensive necrosis treated with conduit resection with diversion.

In patients where the type of anastomotic complication changed over the post-

operative period, the most severe type observed was used in the analysis.

The secondary outcomes were length of hospital and ICU stay, eating and drinking

on discharge and post-operative mortality. The first attempt to manage a leak was

defined as the primary management, with subsequent attempts termed as secondary

and tertiary management, where applicable. The approach to management at each

stage was classified as non-operative management (endoscopic management with

clips, EndoVac, stent etc.) or operative (including washout, anastomotic repair,

disconnection etc.). Anastomotic leak or conduit necrosis management was

assumed to be successful where patients were still alive at 90 days post-

esophagectomy, and had no further treatment recorded.

Ethical Approval & Data Sharing

Ethical approval was dependent on local protocols and was country specific. It was

the responsibility of the local principal investigator of the enrolled center to ensure

appropriate ethical or audit approval was gained prior to commencement of the

study. Ongoing study approval was maintained locally throughout the duration of the

study. In the UK the study was registered at each site as either clinical audit or service

evaluation, as it was an observational study only, and was designed to collect routine,

anonymized data, with no change to the clinical care pathway. Individual patient data

was entered into case report forms (CRFs) which were designed not to deviate from

safe patient care. CRFs were trialed in a two-month pilot to ensure full key data
acquisition. Pilot data was not used in the final analysis. Data input was via a

dedicated encrypted server through the Research Electronic Data Capture (REDCap)

web application. No patient identifiable information was collected. The Birmingham

Surgical Trials Consortium, University of Birmingham, hosted the REDCap system.

Statistical Analysis

Comparisons across the types of anastomotic leak and conduit necrosis were

performed using Kruskal-Wallis tests of Chi-square tests, as applicable. For the

subgroups of patients with anastomotic leaks or conduit necrosis, associations

between a range of factors and the success of the primary management were then

assessed. Nominal variables were analyzed using Fisher’s exact test or Chi-square

test, for factors with two or more than two categories, respectively. Normally distributed

variables were analyzed using independent-samples t-tests, with Mann-Whitney U

tests used for non-normal or ordinal variables. All analyses were performed using IBM

SPSS v22 (IBM Corp. Armonk, NY), with p<0.05 deemed to be indicative of statistical

significance throughout. The alluvial flow diagram was designed using an online

tool20.
Results

Study and Hospital characteristics

From April 2018 to December 2018, 2247 esophagectomies for esophageal cancers

from 137 centers (41 countries) were included into this study. Hospital resources

varied across centers, with 70.9% of centers having an esophageal specialist on-call

for 24 hours and 68.7% of centers having an interventional radiologist on-call every

day for 24 hours. Baseline hospital level data is available in Supplementary Table 1.

Patient characteristics

Patient demographics are detailed in Table 1. In this patient cohort, 78.6% were male

(n=1,767) and 29.1% of patients were >70 years old (n=654). The majority of patients

were overweight or obese (BMI >25 - 55.8%, n=1,251) and 15.6% were current

smokers (n=340). Two thirds of patients were ASA 1-2 (69.4%, n=1,558) and 11.2%

of patients had >2 comorbidities (n=252).

Treatment and Tumor Staging

Data on treatment and tumor staging are presented in Table 1. In this study, 75.1% of

patients underwent neoadjuvant treatment (n=1,687), most commonly with

chemotherapy alone (39.1%) or chemoradiotherapy (35.6%). Minimally invasive

surgery was employed in 57.2% of patients (n=1,275). Intra-thoracic anastomoses

were performed in 77.0% of patients (n= 1,726) and margin-negative resections were

achieved in 96.5% of patients (n=2,168).

Anastomotic Leaks

The overall rate of anastomotic leaks were 14.2% (Table 2), with the highest severity

being Type 1, Type 2 and Type 3 in 7.0%, 3.4%, and 3.8%, respectively (n=158, 76,

85, Table 2). 15.7% of patients with an anastomotic leak had associated conduit

necrosis. Rates of conduit necrosis were 0.5%, 9.2%, 14.5% and 31.0% in those

with no, Type 1, Type 2 and Type 3 anastomotic leaks, respectively (p<0.001, Figure

1). The overall rate of anastomotic leak for an intra-thoracic anastomosis was 12.2%

(211/1726) and in the neck was 20.1% (103/512), (p<0.001, supplementary table 2).

Patients with an intra-thoracic anastomotic leak were significantly more likely to have

a higher leak type, require re-operation, and have longer ITU and overall length of

stay as compared to patients with a neck anastomosis.

Increasing severity of anastomotic leaks (Type 1 vs. Type 2 vs. Type 3) was

associated with a significantly longer length of stay (median: 26 vs. 35 vs. 40 days,

p<0.001), lower rates of eating on discharge (71.5% vs. 67.1% vs. 54.3%, p<0.001),

and higher 90-day mortality rates (3.2% vs. 13.2% vs. 24.7%, p<0.001). The 90-day

mortality rates were comparable in patients with no anastomotic leaks and Type 1

anastomotic leaks (3.3% vs 3.2%, Table 2).

Conduit Necrosis

The overall rate of conduit necrosis was 2.7% (Table 2), with the highest severity

being Type 1, Type 2 and Type 3 in 1.2%, 0.7%, and 0.8%, respectively (n=28, 15,

17, Table 2). 83.3% of patients with conduit necrosis had an associated anastomotic

leak. Rates of anastomotic leak were 12.3%, 82.1%, 86.7% and 82.4% in those with
no, Type 1, Type 2 and Type 3 conduit necrosis, respectively (p<0.001). The overall

rate of conduit for an intra-thoracic anastomosis was 2.2% (38/1726) and in the neck

was 4.3% (22/512), (p<0.013, supplementary table 2). Location of conduit necrosis

did not have a significant impact on outcomes.

Associations with severity were similar to those previously described for anastomotic

leak, with increasing severity of conduit necrosis being associated with significantly

longer lengths of hospital stay, lower rates of eating on discharge, and higher 90 day

mortality rates (all p<0.001, Table 2).

Anastomotic Leak Management

Primary Management

Of the N=329 patients who developed anastomotic leaks or conduit necrosis, primary

management was successful in 69.6% (n=229) of cases. Success rates of primary

management were not found to be significantly associated with any of the patient

factors considered, including age, gender, BMI, ASA grade, comorbidities and the

tumor type and location (Table 3a). However, rates of primary management success

were found to decline significantly with increasing severity of anastomotic leaks, from

96.8% for Type 1 leaks to 37.6% for Type 3 leaks (p<0.001), with a similar association

observed for conduit necrosis (p=0.042, Table 3b). An operative approach to primary

management was also associated with a significantly lower success rate than a non-

operative management (49.3% vs. 75.0%), whilst use of post-operative nutrition was

associated with a significantly higher success rate (p=0.024).

Management Strategies
Further details of the management strategies applied for the N=329 patients who

developed anastomotic leaks or conduit necrosis are summarized in Figure 2, whilst

Figure 3 visualizes of the change in severity and treatment success rates across the

period of leak management. Primary management most commonly used a non-

operative approach (79.0%), and was successful in 69.6% (n=229) cases, with deaths

in 7.6% (N=25). The remaining 75 patients (22.8%) received secondary management,

which was successful in 69.3% (N=52), with a 12.0% (N=9) mortality rate. Tertiary

management was required in 14 patients (4.3% of the cohort), which was successful

in 64.3% (N=9). As such, the cumulative success rates were 69.6%, 85.4% and 88.1%

after primary, secondary and tertiary management, respectively.

Operative Interventions

Across the primary, secondary and tertiary stages of management, a total of 101

operative interventions were performed to treat anastomotic leak/conduit necrosis in

88 patients (N=13 required two operative interventions). Operative interventions were

more commonly observed in those requiring multiple interventions, making up 21.0%

(69/329) of primary management interventions, compared to 32.0% (24/75) and 57.1%

(8/14) of secondary and tertiary interventions, respectively (p=0.002). Washouts were

the most common operative approach to primary management, whilst secondary

operative management was most commonly by esophogostomy.

Operative intervention was successful in 50.5% of interventions (n=51), 29.7%

required an alternative leak management strategy (n=30) and 19.8% died prior to

receiving additional treatment (n=20).

Esophageal Stents

Stents were utilized in a total of 47 interventions in 45 patients (29 primary leak

treatment, 14 secondary leak treatment, four tertiary leak treatment), with metal

covered stents most commonly used (77%, n=36). The majority of patients received

one (66%, n=31) or two (26%, n=12) stents, with a maximum of five stents used. Data

relating to complications were recorded for n=43 of these interventions, for which the

overall complication rate was 30% (n=13), and consisted of stent migration (n=7),

failure to occlude leak (n=3), occlusion (n=1), with other complication types in the

remainder (n=2). No patients developed stent erosion. Stent treatment was successful

in 63.8% of interventions (n=30), 27.7% required an alternative leak management

strategy (n=13) and 8.5% died during treatment (n=4).

EndoVac Therapy

Endovac treatment was used in 25 patients (14 primary leak treatment, 11 secondary

leak treatment), with a total of 137 changes performed (median of 4 changes, range

1-20). No complications were reported for any of the interventions using the Endovac

technique. Endovac therapy was successful in 56% of patients (n=14), 32% required

an alternative leak management strategy (n=8) and 12% died during treatment (n=3).
Discussion

We evaluated post-operative esophagectomy outcomes from 2247 patients across a

global cohort of 137 centers from 41 countries. Our study demonstrated that

increasing anastomotic leak type was associated with significantly increased

postoperative mortality, increased length of stay and lower rates of oral feeding on

discharge. Overall leak management was successful in 88.1% of patients. Primary,

secondary and tertiary leak management strategies maintained equivocal success

rates. Patients requiring multiple leak treatment strategies still achieved reasonable

outcomes. Patients undergoing non-operative leak management and patients

receiving post-operative nutrition were significantly more likely to respond to initial

leak management techniques.

Our study has demonstrated considerably variation in leak management strategies.

Initial leak management strategy success rates were limited to 69.1% of patients;

with significant associated morbidity and mortality was observed for patients with

failed leak management. The evidence base to guide leak management strategies is

limited. Conservative management strategies (nil by mouth, IV antibiotics, IV

antifungals and nutrition) are often employed in hemodynamically and biochemically

stable patients with minimal contamination or no definable collection, whereas

unstable patients with early large volume enteric drainage or extensive conduit

necrosis may undergo emergency surgery. However, most patients do not fit these

polarized clinical presentations and treatment outcomes (whether endoscopic stent

or sponge or other therapies) are significantly more varied providing no clear gold

standard option for leak management. Studies evaluating leak treatment often

demonstrate marked heterogeneity, report data from small cohorts and often lack
important detail regarding leakage characteristics21–23. Several RCTs are in

development randomizing treatment to either covered stent or endovac therapies 24.

In this study only 3% of patients undergoing esophagectomy had endoscopic

treatment for anastomotic complications and therefore this highlights that

randomized trials in this area are going to be extremely challenging to recruit to.

In the absence of reassessment and reintervention a failing leak management

strategy is likely to lead to further morbidity and eventual mortality. Our study has

shown that the success rates of secondary and tertiary leak management were

69.3% and 64.3% respectively confirming that identification of a failing leak

management strategy and active re-intervention is associated with reasonable

outcomes. Currently there is a lack of evidence to support techniques that improve

leak management strategy success rates. In this study post-operative nutritional

support with either nasojejunal or feeding jejunostomy was associated with higher

success rates of primary leak management strategies. It could be hypothesised that

patients with enteral nutrition, rather than TPN or just IV fluids, have better healing

capacity and are better able to recover from the insult of an anastomotic leak.

Post-operative nutrition remains an area controversy in esophageal surgery and

further phase two studies are required to determine the optimal route for early

enteral nutrition25. The recent Nutrient II randomized control trial did not show an

increased frequency or severity of complications with direct oral feeding alone as

compared to tube feeding for 5 days26.

Non-operative primary leak management strategies were significantly more

successful than operative leak management strategies. Operative interventions are

associated with significant mortality in this study. The decision for operative

intervention and subsequent higher failure rate may be a surrogate marker for leak

severity which is otherwise difficult to quantify within the parameters of the current

leak grading structure. This study has shown that intra-thoracic anastomotic leaks

are more severe than an anastomotic leak in the neck, demonstrating higher re-

operation rates, longer admissions and overall higher leak types. Importantly an

anastomotic leak is significantly less likely to occur at an intra-thoracic anastomosis

as compared to a neck anastomosis. The ICAN trial is currently recruiting and aims

to compare anastomotic leakage and postoperative morbidity, mortality, quality of life

and cost-effectiveness between cervical and intra-thoracic anastomoses in minimally

invasive esophagectomy27.

The OGAA study has demonstrated that the ECCG classification of anastomotic leak

severity correlates well with patient outcome. The classification system is defined by

anastomotic leak treatment and provides an excellent way to allow comparison of

datasets. Challenges for clinicians remain however when trying to determine the

appropriate leak management strategy for specific patients. Improvements in the

classification system could be obtained by considering the greater overlap between

anastomotic leak and conduit necrosis which are perceived and treated by many

surgeons as the same complication. This study has shown that for patients with

conduit necrosis there is an associated anastomotic leak in 83% of cases. Adding

additional clinical factors, such as the site of the anastomosis, size of the

anastomotic defect and size of cavity, extent of the leak (contained or uncontained),

and degree of contamination and sepsis may also guide treatment. The Treatment of

Anastomotic Leakage After Esophagectomy (TENTACLE) study aims to investigate

what factors contribute to anastomotic leakage severity and will seek to compose an

evidence based anastomotic leakage severity score to help in the management of

patients28.

High rates of complications are still seen in high volume selected centers from uniform

healthcare systems as reported in ECCG and DUCA, however these units have

excellent resources available to salvage patients and limit poor outcomes1,2. Failure to

rescue and leak management strategies have increasingly been recognized as an

area of academic interest in a specialty with high morbidity and mortality, further

corroboration and research is required to optimize outcomes post

esophagectomy29,30. The OGAA study provided an open inclusive center recruitment

policy allowing any international center to provide data. This sought to identify whether

outcomes as reported by ECCG and DUCA are achievable in an unselected wider

global setting. Outcome after major surgery is heavily influenced by resources, both

financial and volume related and despite these challenges the OGAA study has

demonstrated that esophagectomy can be performed safely and consistently across

an international cohort of esophagogastric resection centers.

This study has some strengths, including its prospective nature and robust electronic

data capture form. A study duration of 1 year was decided to improve case

ascertainment, minimize reporting variability and provide a contemporaneous

snapshot of practice. The study was limited by the total number of patients receiving

endoscopic management and therefore comparative analysis of the outcomes of

individual leak management strategies (e.g. stent vs Endovac) was not possible. Data

was verified by each unit’s PI however no specific data verification process was
performed. Previous data verification in national and international observational

studies has shown excellent accuracy in reporting 31,32.

Conclusion

The Oesophago-Gastric Anastomosis Audit has shown that increasing anastomotic

leak type was associated with significantly increased postoperative mortality and

overall poorer patient outcomes. There is considerable overlap between anastomotic

leak and conduit necrosis. Enteral nutritional support was associated with higher

success rates of primary leak management strategies. Initial leak management

strategy success rates were limited to 69.1% of patients; with significant associated

morbidity and mortality was observed for patients with failed leak management. It is

important that in a failing leak management strategy that active re-intervention is

initiated as this can successfully treat anastomotic complications.

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31. Bhangu A, Chapman SJ, Glasbey J, et al. Impact of postoperative non-

 steroidal anti-inflammatory drugs on adverse events after gastrointestinal

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 Table 1 Baseline demographics, treatments and outcomes of patients undergoing

esophagectomy for esophageal cancers

N Statistic N Statistic
Demographics Treatment
Age (Years) 2247 63.9 ± 10.5 Neoadjuvant Therapy 2247
Gender (% Male) 2247 1767 (78.6%) None 560 (24.9%)
BMI (kg/m2) 2240 26.2 ± 5.3 Chemoradiotherapy 801 (35.6%)
ASA Grade 2246 Chemotherapy alone 879 (39.1%)
1 298 (13.3%) Radiotherapy alone 7 (0.3%)
2 1260 (56.1%) Anastomosis Technique 2243
3 666 (29.7%) Circular stapled 1164 (51.9%)
4 22 (1.0%) Handsewn 609 (27.2%)
ECOG Status 2241 Linear Stapled 470 (21.0%)
0 1364 (60.9%) Anastomosis Site 2238
1 735 (32.8%) Intra-Thoracic 1726 (77.1%)
2 123 (5.5%) Neck 512 (22.9%)
3 16 (0.7%) Abdominal Phase 2234
4 3 (0.1%) Minimally Invasive 1197 (53.6%)
Charlson Comorbidity Index 2247 6 (5 - 6) Open 1037 (46.4%)
COPD 2247 307 (13.7%) Thoracic Phase 2241
Diabetes 2247 271 (12.1%) Minimally Invasive 739 (33.0%)
Cardiovascular Disease 2247 342 (15.2%) Open 1376 (61.4%)
Smoking Status 2183 Transhiatal 126 (5.6%)
Never 842 (38.6%) Positive Margins 2247 408 (18.2%)
Ex 1001 (45.9%) Post-Operative Nutrition 2246
Current 340 (15.6%) None 860 (38.3%)
Tumour Type 2246 Feeding Jejunostomy 1103 (49.1%)
Adenocarcinoma 1653 (73.6%) Nasojejunal tube 283 (12.6%)
Squamous Cell Carcinoma 534 (23.8%) Outcomes
Other 59 (2.6%) Anastomotic Leak 2247
Tumour Location 2246 None 1928 (85.8%)
Distal / Siewert 1-2 1883 (83.8%) Type 1 158 (7.0%)
Middle 241 (10.7%) Type 2 76 (3.4%)
Proximal 57 (2.5%) Type 3 85 (3.8%)
Siewert 3 65 (2.9%) Conduit Necrosis 2246
Overall Stage* 2223 None 2186 (97.3%)
0 324 (14.6%) Type 1 28 (1.2%)
1 343 (15.4%) Type 2 15 (0.7%)
2 350 (15.7%) Type 3 17 (0.8%)
3 737 (33.2%) Return to Theatre 2247 269 (12.0%)
4 469 (21.1%) Total LOS (Days) 2234 12 (9 - 18)
Pre-Operative Nutrition 2245 Total ICU Stay (Days) 2234 3 (2 - 6)
None 1125 (50.1%) Eating on Discharge 2238 1967 (87.9%)
Oral Supplements 836 (37.2%) 30 Day Readmission 2168 249 (11.5%)
Enteral Nutrition 248 (11.0%) 30 Day Mortality 2247 71 (3.2%)
Parenteral Nutrition 36 (1.6%) 90 Day Mortality 2247 100 (4.5%)
Table 2 Outcomes of patients with anastomotic leak and conduit necrosis severity who underwent esophagectomy for esophageal

cancer

None Type 1 Type 2 Type 3 p-Value

Anastomotic Leak
N 1928 158 76 85 -
POD of Leak N/A 7 (5-9) 7 (5-11) 6 (4-9) 0.071
POD of Management N/A 7 (5-10) 7 (5-11) 7 (4-10) 0.190
Return to Theatre 7.0% (135/1928) 11.4% (18/158) 40.8% (31/76) 100% (85/85) <0.001
Total LOS (Days) 11 (9-15) 26 (17-35) 35 (24-53) 40 (21-60) <0.001
Total ICU Stay (Days) 3 (1-6) 5 (2-11) 8 (2-22) 17 (8-31) <0.001
Eating on Discharge 91.5% (1759/1923) 71.5% (113/158) 67.1% (51/76) 54.3% (44/81) <0.001
30 Day Readmission 10.4% (196/1886) 16.4% (25/152) 23.4% (15/64) 19.7% (13/66) <0.001
30 Day Mortality 2.1% (41/1928) 1.9% (3/158) 10.5% (8/76) 22.4% (19/85) <0.001
90 Day Mortality 3.3% (64/1928) 3.2% (5/158) 13.2% (10/76) 24.7% (21/85) <0.001
Conduit Necrosis
N 2186 28 15 17 -
POD of Necrosis N/A 8 (5-10) 5 (2-7) 7 (4-14) 0.171
POD of Management N/A 7 (5-10) 4 (4-7) 6 (3-8) 0.355
Return to Theatre 10.3% (225/2186) 46.4% (13/28) 86.7% (13/15) 100% (17/17) <0.001
Total LOS (Days) 12 (9-17) 31 (25-53) 44 (25-55) 45 (34-82) <0.001
Total ICU Stay (Days) 3 (2-6) 9 (2-23) 16 (10-42) 21 (19-40) <0.001
Eating on Discharge 89.2% (1943/2179) 46.4% (13/28) 50.0% (7/14) 23.5% (4/17) <0.001
30 Day Readmission 11.5% (244/2124) 18.2% (4/22) 9.1% (1/11) 0.0% (0/11) 0.483
30 Day Mortality 2.6% (56/2186) 14.3% (4/28) 26.7% (4/15) 35.3% (6/17) <0.001
90 Day Mortality 3.9% (85/2186) 14.3% (4/28) 26.7% (4/15) 35.3% (6/17) <0.001
Data are reported as % (n/N), with p-values from chi-square tests, or as median (interquartile range), with p-values from Kruskal-Wallis tests, as applicable.
Bold p-values are significant at p<0.05. POD – post operative day, LOS- length of stay, ICU- intensive care unit.
Table 3a – Associations between patient factors and successful primary
management of anastomotic leaks or conduit necrosis

Successful Primary
Management
N No Yes p-Value
Age (Years) 329 64.1 ± 10.4 63.5 ± 10.2 0.591
Gender 329 0.753
Female 16 (28.1%) 41 (71.9%)
Male 84 (30.9%) 188 (69.1%)
BMI (kg/m2) 326 26.4 ± 5.4 26.5 ± 5.1 0.868
ASA Grade 328 0.890*
1 15 (36.6%) 26 (63.4%)
2 42 (28.2%) 107 (71.8%)
3 42 (31.1%) 93 (68.9%)
4 1 (33.3%) 2 (66.7%)
ECOG Status 327 0.490*
0 51 (29.1%) 124 (70.9%)
1 37 (29.8%) 87 (70.2%)
2 9 (40.9%) 13 (59.1%)
3 2 (33.3%) 4 (66.7%)
Charlson Comorbidity Index 329 6 (5-7) 6 (5-7) 0.887*
COPD 329 0.577
No 74 (29.6%) 176 (70.4%)
Yes 26 (32.9%) 53 (67.1%)
Diabetes 329 0.734
No 87 (30.9%) 195 (69.1%)
Yes 13 (27.7%) 34 (72.3%)
Cardiovascular Disease 329 0.560
No 81 (31.3%) 178 (68.7%)
Yes 19 (27.1%) 51 (72.9%)
Smoking Status 321 0.492
Never 24 (26.1%) 68 (73.9%)
Ex 53 (32.3%) 111 (67.7%)
Current 22 (33.8%) 43 (66.2%)
Tumour Type 329 0.621
Adenocarcinoma 71 (32.1%) 150 (67.9%)
Squamous Cell Carcinoma 25 (26.9%) 68 (73.1%)
Other 4 (26.7%) 11 (73.3%)
Tumour Location 329 0.573
Distal / Siewert 1-2 80 (31.6%) 173 (68.4%)
Middle 11 (22.9%) 37 (77.1%)
Proximal 6 (37.5%) 10 (62.5%)
Siewert 3 3 (25.0%) 9 (75.0%)
Overall Stage (Pathology) 324 0.279*
0 14 (29.2%) 34 (70.8%)
1 22 (43.1%) 29 (56.9%)
2 16 (31.4%) 35 (68.6%)
3 31 (27.0%) 84 (73.0%)
4 17 (28.8%) 42 (71.2%)
Categorical data are reported as N (row N %), with p-values from Fisher’s exact test or Chi-square test for factors with two or
more than two categories, respectively, unless stated otherwise. Continuous data are reported as mean ± SD, with p-values
from independent samples t-tests, or as median (interquartile range), with p-values from Mann-Whitney U tests, as applicable.
Bold p-values are significant at p<0.05. *p-Value from Mann-Whitney U test, as the factor is ordinal.
ASA = American Society Anaesthesiology, ECOG = Eastern Cooperative Oncology Group performance status, COPD =
Chronic Obstructive Pulmonary Disease
Table 3b – Associations between treatment factors and successful primary

management of anastomotic leaks or conduit necrosis

Successful Primary
Management
N No Yes p-Value
Pre-Operative Nutrition 329 0.090
None 61 (34.5%) 116 (65.5%)
Oral Supplements 32 (29.9%) 75 (70.1%)
Enteral Nutrition 5 (13.5%) 32 (86.5%)
Parenteral Nutrition 2 (25.0%) 6 (75.0%)
Neoadjuvant Therapy 329 0.774
None 29 (31.9%) 62 (68.1%)
Chemoradiotherapy 38 (27.3%) 101 (72.7%)
Chemotherapy alone 32 (33.3%) 64 (66.7%)
Radiotherapy alone 1 (33.3%) 2 (66.7%)
Anastomosis Technique 326 0.087
Circular stapled 49 (34.8%) 92 (65.2%)
Handsewn 27 (22.7%) 92 (77.3%)
Linear Stapled 22 (33.3%) 44 (66.7%)
Anastomosis Site 324 0.120
Intra-thoracic 72 (32.7%) 148 (67.3%)
Neck 25 (24.0%) 79 (76.0%)
Abdominal Phase 329 0.335
Minimally Invasive 60 (32.8%) 123 (67.2%)
Open 40 (27.4%) 106 (72.6%)
Thoracic Phase 328 0.557
Minimally Invasive 45 (33.6%) 89 (66.4%)
Open 49 (28.8%) 121 (71.2%)
Transhiatal 6 (25.0%) 18 (75.0%)
Positive Margins 329 0.633
No 85 (31.0%) 189 (69.0%)
Yes 15 (27.3%) 40 (72.7%)
Post-Operative Nutrition 329 0.024
None 44 (36.7%) 76 (63.3%)
Feeding Jejunostomy 52 (29.5%) 124 (70.5%)
Nasojejunal tube 4 (12.1%) 29 (87.9%)
Anastomotic Leak Type** 319 <0.001*
Type 1 5 (3.2%) 153 (96.8%)
Type 2 39 (51.3%) 37 (48.7%)
Type 3 53 (62.4%) 32 (37.6%)
Conduit Necrosis Type** 60 0.042*
Type 1 8 (28.6%) 20 (71.4%)
Type 2 7 (46.7%) 8 (53.3%)
Type 3 10 (58.8%) 7 (41.2%)
Primary Management Approach 329 <0.001
Non-Operative 65 (25.0%) 195 (75.0%)
Operative 35 (50.7%) 34 (49.3%)
Categorical data are reported as N (row N %), with p-values from Fisher’s exact test or Chi-square test for factors with two or
more than two categories, respectively, unless stated otherwise. Continuous data are reported as mean ± SD, with p-values
from independent samples t-tests, or as median (interquartile range), with p-values from Mann-Whitney U tests, as applicable.
Bold p-values are significant at p<0.05. *p-Value from Mann-Whitney U test, as the factor is ordinal. **In those patients with
conduit necrosis/anastomotic leak.
Figure 1 – Correlation between anastomotic leak and conduit necrosis
Figure 2 – Flowchart showing anastomotic leak and conduit necrosis management in

the OGAA study

Figure 3 Alluvial flow diagram showing the treatment strategies and re-intervention

requirements and overall outcome of patients with anastomotic leak/conduit necrosis

Initial Outcome of
AL / CN Primary
Severity Management

n=158 Successful 69.6%

Type 1
n=197

Outcome of
n=37 Secondary
Management

n=34
n=39
Successful 69.3% Outcome of
Type 2 Tertiary
n=63 n=27 n=13
Management
Type 2- 15.5% n=4
n=10 Successful 64.3%
n=14 n=6 n=5
n=2 Type 3- 10.7%
n=6 n=2 Unsuccessful 7.1%
Type 2- 8.0% n=3
Type 3 n=9
n=9
Type 3- 7.3% n=4
Death 28.6%
n=69 n=6 n=4
n=1
n=7 Death 7.6% n=5 Death 12.0%
n=12
Supplementary Table 1 Baseline characteristics of centers of patients undergoing

esophagectomy for esophageal cancers

Factor Statistic
Country*
Great Britain 37 (27.0%)
Spain 8 (5.8%)
Australia 7 (5.1%)
Italy 6 (4.4%)
Portugal 6 (4.4%)
Germany 5 (3.6%)
Romania 5 (3.6%)
Turkey 5 (3.6%)
Denmark 4 (2.9%)
Ireland 4 (2.9%)
Netherlands 4 (2.9%)
New Zealand 4 (2.9%)
Pakistan 4 (2.9%)
United States of America 4 (2.9%)
Others 34 (24.8%)
Number of Consultant Surgeons 3 (2 - 4)
Number of Hospital Beds 700 (350 - 1020)
Number of ICU Beds 24 (14 - 36)
Esophageal Surgeon On-Call Rota
None 17 (12.7%)
Weekdays Daytime 13 (9.7%)
Weekdays 24 hours 3 (2.2%)
Every day Daytime 6 (4.5%)
Every day 24 hours 95 (70.9%)
Interventional Radiology On-Call
None 18 (13.4%)
Weekdays Daytime 16 (11.9%)
Weekdays 24 hours 1 (0.7%)
Every day Daytime 7 (5.2%)
Every day 24 hours 92 (68.7%)
ERAS Protocol 67 (50.0%)
ERAS Nurse 32 (23.9%)
Dedicated Physiotherapy Input
None 20 (14.9%)
Weekdays - Daily 46 (34.3%)
Weekdays - Twice Daily 14 (10.4%)
Every day - Daily 41 (30.6%)
Every day - Twice Daily 13 (9.7%)
Data are reported as N (%), or as median (interquartile range), and are based on N=134 due to
missing data for N=3 centers, unless stated otherwise. * For all centers (N=137).
Supplementary Table 2– Outcomes of patients by anastomotic leak or conduit necrosis who underwent esophagectomy for esophageal cancer

Anastomotic Leak (Anastomosis Site) p-Values

None Yes (Intra-thoracic) Yes (Neck) Overall Site
Anastomotic Leak
N 1925 211 103 - -
POD of Leak N/A 7 (5-11) 7 (5-9) N/A 0.804
POD of Management N/A 7 (5-11) 7 (5-9) N/A 0.762
Anastomotic Leak Type - - - N/A <0.001
Type 1 N/A 42.2% (89/211) 65.0% (67/103) - -
Type 2 N/A 31.3% (66/211) 9.7% (10/103) - -
Type 3 N/A 26.5% (56/211) 25.2% (26/103) - -
Return to Theatre 7.0% (135/1925) 46.9% (99/211) 30.1% (31/103) <0.001 0.004
Total LOS (Days) 11 (9-15) 32 (20-52) 27 (20-37) <0.001 0.007
Total ICU Stay (Days) 3 (1-6) 8 (3-21) 5 (2-15) <0.001 0.024
Eating on Discharge 91.5% (1756/1920) 69.2% (146/211) 61.0% (61/100) <0.001 0.159
30 Day Readmission 10.4% (195/1883) 19.1% (36/188) 17.6% (16/91) <0.001 0.753
30 Day Mortality 2.1% (41/1925) 7.1% (15/211) 12.6% (13/103) <0.001 0.108
90 Day Mortality 3.3% (64/1925) 9.5% (20/211) 13.6% (14/103) <0.001 0.271
Conduit Necrosis
N 2181 38 22 - -
POD of Necrosis N/A 6 (4-10) 8 (5-10) N/A 0.396
POD of Management N/A 6 (4-9) 7 (4-10) N/A 0.637
Conduit Necrosis Type - - - N/A 0.060
Type 1 N/A 50.0% (19/38) 40.9% (9/22) - -
Type 2 N/A 31.6% (12/38) 13.6% (3/22) - -
Type 3 N/A 18.4% (7/38) 45.5% (10/22) - -
Return to Theatre 10.3% (224/2181) 76.3% (29/38) 63.6% (14/22) <0.001 0.294
Total LOS (Days) 12 (9-17) 42 (25-68) 35 (30-50) <0.001 0.769
Total ICU Stay (Days) 3 (2-6) 16 (4-27) 19 (6-31) <0.001 0.757
Eating on Discharge 89.2% (1939/2174) 39.5% (15/38) 42.9% (9/21) <0.001 0.800
30 Day Readmission 11.4% (242/2119) 10.0% (3/30) 14.3% (2/14) 0.917 0.677
30 Day Mortality 2.6% (56/2181) 18.4% (7/38) 31.8% (7/22) <0.001 0.237
90 Day Mortality 3.9% (85/2181) 18.4% (7/38) 31.8% (7/22) <0.001 0.343
Data are reported as % (n/N), with p-values from chi-square tests, or as median (interquartile range), with p-values from Mann-Whitney U / Kruskal-Wallis tests, as applicable. The “Overall” p-
value represents a comparison across all three groups, whilst the “Site” comparison compares between anastomotic leaks/conduit necrosis in the intra-thoracic vs. neck. Bold p-values are
significant at p<0.05. Patients where the anastomosis site was not recorded were excluded from the analysis. POD – post operative day, LOS- length of stay, ICU- intensive care
Appendix 1

OGAA Author List (All to be pubmed citable)

Writing Committee: Evans RPT, Kamarajah SK, Bundred J, Siaw-Acheampong K,

Nepogodiev D, Hodson J, Gossage J, Vohra R, van Hillegersberg R, Singh P,

Griffiths EA

Data Analysis: Hodson J, Kamarajah SK, Griffiths EA

Steering Committee: Alderson D, Bundred J, Evans RPT, Gossage J, Griffiths EA,

Jefferies B, Kamarajah SK, McKay S, Mohamed I, Nepogodiev D, Siaw-

Acheampong K, Singh P, van Hillegersberg R, Vohra R, Wanigasooriya K,

Whitehouse T.

National Leads: Gjata A (Albania), Moreno JI (Argentina), Takeda FR (Brazil),

Kidane B (Canada), Guevara Castro R (Colombia), Harustiak T (Czech Republic),

Bekele A (Ethiopia), Kechagias A (Finland), Gockel I (Germany), Kennedy A

(Ireland), Da Roit A (Italy), Bagajevas A (Lithuania), Azagra JS (Luxembourg),

Mahendran HA (Malaysia), Mejía-Fernández L (Mexico), Wijnhoven BPL

(Netherlands), El Kafsi J (New Zealand), Sayyed RH (Pakistan), Sousa M (Portugal),

Sampaio AS (Portugal), Negoi I (Romania), Blanco R (Spain), Wallner B (Sweden),

Schneider PM (Switzerland), Hsu PK (Taiwan), Isik A (Turkey)

Site Leads:

Gananadha S (The Canberra Hospital, Australia); Wills V (John Hunter Hospital,

Australia); Devadas M (Nepean Hospital, Australia); Duong C (Peter MacCallum

Cancer Centre, Australia); Talbot M (St George Public and Private Hospitals,

Australia); Hii MW (St Vincent's Hospital Melbourne, Australia); Jacobs R (Western

Hospital, Victoria, Australia); Andreollo NA (Unicamp University Hospital, Brazil);

Johnston B (Saint John Regional Hospital, Canada); Darling G (Toronto General

Hospital, University Health Network, Canada); Isaza-Restrepo A (Hospital

Universitario Mayor Mederi-Universidad del Rosario, Colombia); Rosero G (Hospital

San Ignacio-Universidad Javeriana, Colombia); Arias- Amézquita F (University

Hospital Fundacion Santafe de Bogota, Colombia); Raptis D (University Clinic of

Erlangen, Germany); Gaedcke J (Medical Unversity Goettingen, Germany); Reim D

(Klinikum Rechts der Isar der TU München, Germany); Izbicki J (University Hospital

Hamburg Eppendorf, Germany); Dikinis S (Aalborg University Hospital, Denmark);

Kjaer DW (Aarhus University Hospital, Denmark); Larsen MH (Odense University

Hospital, Denmark); Achiam MP (Copenhagen University hospital Rigshospitalet,

Denmark); Saarnio J (Oulu University Hospital, Finland); Theodorou D (Hippokration

General Hospital University of Athens, Greece); Liakakos T (Laikon General

Hospital, Greece); Korkolis DP (St. Savvas Cancer Hospital, Greece); Robb WB

(Beaumont Hospital, Ireland); Collins C (University Hospital Galway, Ireland);

Murphy T (Mercy University Hospital, Ireland); Reynolds J (St James's Hospital,

Dublin, Ireland); Tonini V (St. Orsola Hospital- University of Bologna, Italy); Migliore

M (Polyclinic Hospital University of Catania, Italy); Bonavina L (University of Milano,

IRCCS Policlinico San Donato, Department of General and Foregut Surgery, Italy);

Valmasoni M (Padova University Hospital - Clinica Chirurgica 3, Italy); Bardini R

(Padova University Hospital- General Surgery Department, Italy); Weindelmayer J

(Verona Borgo Trento Hospital, Italy); Terashima M (Shizioka Cancer Centre,

Japan); White RE (Tenwek Hospital, Kenya); Alghunaim E (Chest Diseases Hospital,

Kuwait); Elhadi M (Tripoli, Libya); Leon-Takahashi AM (National Cancer Institute,

Mexico); Medina-Franco H (National Institute of Medical Science and Nutrition

Salvador Zubirán, Mexico); Lau PC (University Malaya Medical Centre, Malaysia);

Okonta KE (Carez Hospital & University of Port-Harcourt Teaching Hospital,

Nigeria); Heisterkamp J (Elisabeth-TweeSteden Ziekenhuis Hospital, Netherlands);

Rosman C (Radboudumc, Netherlands); van Hillegersberg R (UMC Utrecht,

Netherlands); Beban G (Auckland City Hospital, New Zealand); Babor R

(Middlemore Hospital, New Zealand); Gordon A (Palmerston North Hospital, New

Zealand); Rossaak JI (Tauranga Hospital, Bay of Plenty District Health Board, New

Zealand); Pal KMI (Aga Khan University Hospital, Pakistan); Qureshi AU (Services

Institute of Medical Sciences, Lahore, Pakistan); Naqi SA (Mayo Hospital, Lahore,

Pakistan); Syed AA (Shaukat Khanum Memorial Cancer Hospital & Research Centre

Lahore, Pakistan); Barbosa J (Centro Hospitalar São João, Portugal); Vicente CS

(Centro Hospitalar Lisboa Central, Portugal); Leite J (Coimbra University Hospital,

Portugal); Freire J (Hospital Santa Maria, Portugal); Casaca R (Instituto Português

de Oncologia de Lisboa, Portugal); Costa RCT (Instituto Português de Oncologia do

Porto, Portugal); Scurtu RR (University Emergency Cluj County Hospital, Romania);

Mogoanta SS (Emergency County Hospital of Craiova, Romania); Bolca C (Marius

Nasta' National Institute of Pneumology, Romania); Constantinoiu S (St. Mary

Clinical Hospital, Romania); Sekhniaidze D (Tyumen Regional Hospital, Russia);

Bjelović M (Department for Minimally Invasive Upper Digestive Surgery, University

Hospital for Digestive Surgery, Clinical Center of Serbia, Belgrade, Serbia); So JBY

(National University Hospital, Singapore); Gačevski G (University Hospital Maribor,

Slovenia); Loureiro C (University Hospital of Basurto (Bilbao), Spain); Pera M

(Hospital Universitario del Mar, Spain); Bianchi A (Palma de Mallorca, Spain);

Moreno Gijón M (Hospital Universitario Central de Asturias, Spain); Martín

Fernández J (Hospital General Universitario De Ciudad Real, Spain); Trugeda

Carrera MS (Hospital Universitario Marqués de Valdecilla, Spain); Vallve-Bernal M

(Hospital Universitario Nuestra Señora de Candelaria, Spain); Cítores Pascual MA

(Hospital Universitario Río Hortega de Valladolid, Spain); Elmahi S (Shaab Teaching

Hospital, Sudan), Halldestam I (University Hospital Linköping, Sweden); Hedberg J

(Uppsala University Hospital, Sweden); Stefan M (Geneva University Hospital,

Switzerland); Gutknecht S (Triemli Hospital Zurich, Switzerland); Tez M (Ankara

Numune Hospital, Turkey); Guner A (Karadeniz Technical University, Turkey);

Tirnaksiz MB (Hacettepe University Hospital, Turkey); Colak E (University of Health

Sciences, Samsun Training and Research Hospital, Turkey); Sevinç B (Usak

University Training and Research Hospital, Turkey); Hindmarsh A (Addenbrooke's

Hospital, Cambridge, United Kingdom (UK)); Khan I (Aintree University Hospital,

Liverpool, UK); Khoo D (Barking Havering and Redbridge NHS Trust, UK); Byrom R

(Royal Bournemouth Hospital, UK); Gokhale J (Bradford Royal Infirmary, UK);

Wilkerson P (University Hospitals Bristol NHS Foundation Trust, UK); Jain P (Castle

Hill Hospital, UK); Chan D (University Hospital of Coventry, UK); Robertson K

(University Hospital Crosshouse, UK); Iftikhar S (Royal Derby Hospital, UK);

Skipworth R (Edinburgh Royal Infirmary, UK); Forshaw M (Glasgow Royal Infirmary,

UK); Higgs S (Gloucester Royal Hospital, UK); Gossage J (Guy's and St Thomas's

Hospitals, UK); Nijjar R (Heartlands Hospital, UK); Viswanath YKS (James Cook

University Hospital, UK); Turner P (Lancashire Teaching Hospitals NHS Foundation

Trust, UK); Dexter S (Leeds Teaching Hospitals NHS Trust, UK); Boddy A

(University Hospitals of Leicester NHS Trust, UK); Allum WH (Royal Marsden

Hospital, UK); Oglesby S (Ninewells Hospital, UK); Cheong E (Norfolk and Norwich

University Hospital, UK); Beardsmore D (University Hospital of North Midlands, UK);

Vohra R (Nottingham University Hospital, UK); Maynard N (Oxford University

Hospitals, UK); Berrisford R (Plymouth Hospitals NHS Trust, UK); Mercer S (Queen

Alexandra Hospital, Portsmouth, UK); Puig S (Queen Elizabeth Hospital

Birmingham, UK); Melhado R (Salford Royal Foundation Trust, UK); Kelty C

(Sheffield Teaching Hospitals NHS Foundation Trust, UK); Underwood T (University

Hospital Southampton NHS Foundation Trust, UK); Dawas K (University College

Hospital, UK); Lewis W (University Hospital of Wales, UK); Al-Bahrani A (Watford

General Hospital); Bryce G (University Hospital Wishaw, UK); Thomas M (Mayo

Clinic in Florida, United States of America (USA)); Arndt AT (Rush University

Medical Center, USA); Palazzo F (Thomas Jefferson University, USA); Meguid RA

(University of Colorado Hospital, USA)

Collaborators:

Fergusson J, Beenen E, Mosse C, Salim J (The Canberra Hospital, Australia);

Cheah S, Wright T, Cerdeira MP, McQuillan P (John Hunter Hospital, Australia);

Richardson M, Liem H ( Nepean Hospital, Australia); Spillane J, Yacob M, Albadawi

F, Thorpe T, Dingle A, Cabalag C (Peter MacCallum Cancer Centre, Australia); Loi

K, Fisher O, Ward S, Read M, Johnson M (St Vincent's Hospital Melbourne,

Australia); Bassari R, Bui H (Western Hospital, Victoria); Cecconello I, Sallum RAA,

da Rocha JRM (Hospital das Clinicas, University of Sao Paulo School of Medicine,

Brazil); Lopes LR, Tercioti V Jr, Coelho JDS, Ferrer JAP (Unicamp University

Hospital, Brazil); Buduhan G, Tan L, Srinathan S (Health Sciences Centre

(Winnipeg)); Shea P (Saint John Regional Hospital, Canada); Yeung J, Allison F,

Carroll P (Toronto General Hospital, University Health Network, Canada); Vargas-

Barato F, Gonzalez F, Ortega J, Nino-Torres L, Beltrán-García TC (Hospital

Universitario Mayor Mederi-Universidad del Rosario, Colombia); Castilla L, Pineda M

(Hospital San Ignacio-Universidad Javeriana, Colombia); Bastidas A, Gómez-

Mayorga J, Cortés N, Cetares C, Caceres S, Duarte S (University Hospital

Fundacion Santafe de Bogota, Colombia); Pazdro A, Snajdauf M, Faltova H,

Sevcikova M (Motol University Hospital, Prague, Czech Republic); Mortensen PB

(Aalborg University Hospital, Denmark); Katballe N, Ingemann T, Morten B,

Kruhlikava I (Aarhus University Hospital, Denmark); Ainswort AP, Stilling NM,

Eckardt J (Odense University Hospital, Denmark); Holm J, Thorsteinsson M,

Siemsen M, Brandt B (Copenhagen University hospital Rigshospitalet, Denmark);

Nega B, Teferra E, Tizazu A (Tikur Anbessa Specialized Hospital, Ethiopa); Kauppila

JS, Koivukangas V, Meriläinen S (Oulu University Hospital, Finland); Gruetzmann R,

Krautz C, Weber G, Golcher H (University Clinic of Erlangen, Germany); Emons G,

Azizian A, Ebeling M (Medical University Goettingen, Germany); Niebisch S, Kreuser

N, Albanese G, Hesse J (Universitätklinium Leipzig, Germany); Volovnik L, Boecher

U (Klinikum Rechts der Isar der TU München, Germany); Reeh M (University

Hospital Hamburg Eppendorf, Germany); Triantafyllou S (Hippokration General

Hospital University of Athens, Greece); Schizas D, Michalinos A, Mpali E, Mpoura M,

Charalabopoulos A (Laikon General Hospital, Greece); Manatakis DK, Balalis D (St.

Savvas Cancer Hospital, Greece); Bolger J, Baban C, Mastrosimone A (Beaumont

Hospital, Ireland); McAnena O, Quinn A (University Hospital Galway, Ireland); Ó

Súilleabháin CB, Hennessy MM, Ivanovski I, Khizer H (Mercy University Hospital,

Ireland); Ravi N, Donlon N (St James's Hospital, Dublin, Ireland); Cervellera M,

Vaccari S, Bianchini S, Sartarelli l (St. Orsola Hospital- University of Bologna, Italy);

Asti E, Bernardi D (University of Milano, IRCCS Policlinico San Donato, Department

of General and Foregut Surgery, Italy); Merigliano S, Provenzano L (Padova

University Hospital - Clinica Chirurgica, Italy); Scarpa M, Saadeh L, Salmaso B

(Padova University Hospital- General Surgery Department, Italy); De Manzoni G,

Giacopuzzi S, La Mendola R, De Pasqual CA (Verona Borgo Trento Hospital, Italy);

Tsubosa Y, Niihara M, Irino T, Makuuchi R, Ishii K (Shizioka Cancer Centre, Japan);

Mwachiro M, Fekadu A, Odera A, Mwachiro E (Tenwek Hospital, Kenya); AlShehab

D (Chest diseases hospital, Kuwait); Ahmed HA, Shebani AO, Elhadi A, Elnagar FA,

Elnagar HF (Tripoli, Libya); Makkai-Popa ST (Centre Hospitalier de Luxembourg,

Luxembourg); Wong LF (University Malaya Medical Centre, Malaysia); Yunrong T,

Thanninalai S, Aik HC, Soon PW, Huei TJ (Hospital Sultanah Aminah, Malaysia);

Basave HNL ( National Cancer Institute, Mexico); Cortés-González R (Instituto

Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán', Mexico); Lagarde SM,

van Lanschot JJB, Cords C (Erasmus University Medical Center, Rotterdam,

Netherlands); Jansen WA, Martijnse I, Matthijsen R (Elisabeth-TweeSteden

Ziekenhuis Hospital, Netherlands); Bouwense S, Klarenbeek B, Verstegen M, van

Workum F (Radboudumc, Netherlands); Ruurda JP, van der Sluis PC, de Maat M

(UMC Utrecht, Netherlands); Evenett N, Johnston P, Patel R (Auckland City

Hospital, New Zealand); MacCormick A (Middlemore Hospital, New Zealand); Young

M (Palmerston North Hospital); Smith B (Tauranga Hospital, Bay of Plenty District

Health Board, New Zealand); Ekwunife C (Carez Hospital & University of Port-

Harcourt Teaching Hospital, Nigeria); Memon AH, Shaikh K, Wajid A (Aga Khan

University Hospital, Pakistan); Khalil N, Haris M, Mirza ZU, Qudus SBA (Services

Institute of Medical Sciences, Lahore, Pakistan); Sarwar MZ, Shehzadi A, Raza A,

Jhanzaib MH (Mayo Hospital, Lahore, Pakistan); Farmanali J, Zakir Z (Patel

Hospital, Pakistan); Shakeel O, Nasir I, Khattak S, Baig M, Noor MA, Ahmed HH,

Naeem A (Shaukat Khanum Memorial Cancer Hospital & Research Centre Lahore,

Pakistan); Pinho AC, da Silva R (Centro Hospitalar Lisboa Central, Portugal),

Bernardes A, Campos JC (Coimbra University Hospital, Portugal); Matos H, Braga T

(Hospital Santa Maria, Portugal); Monteiro C, Ramos P, Cabral F (Instituto

Português de Oncologia de Lisboa, Portugal); Gomes MP, Martins PC, Correia AM,
Videira JF (Instituto Português de Oncologia do Porto, Portugal); Ciuce C,

Drasovean R, Apostu R, Ciuce C (University Emergency Cluj County Hospital,

Romania); Paitici S, Racu AE, Obleaga CV (Emergency County Hospital of Craiova,

Romania); Beuran M, Stoica B, Ciubotaru C, Negoita V (Emergency Hospital of

Bucharest, Romania); Cordos I (Marius Nasta' National Institute of Pneumology,

Romania); Birla RD, Predescu D, Hoara PA, Tomsa R (St. Mary Clinical Hospital,

Romania); Shneider V, Agasiev M, Ganjara I (Tyumen Regional Hospital, Russia);

Gunjić D, Veselinović M, Babič T (Department for Minimally Invasive Upper Digestive

Surgery, University Hospital for Digestive Surgery, Clinical Center of Serbia,

Belgrade, Serbia); Chin TS, Shabbir A, Kim G (National University Hospital,

Singapore); Crnjac A, Samo H (University Hospital Maribor, Slovenia); Díez del Val I,

Leturio S (University Hospital of Basurto (Bilbao), Spain); Díez del Val I, Leturio S,

Ramón JM, Dal Cero M, Rifá S, Rico M (Hospital Universitario del Mar, Spain);

Pagan Pomar A, Martinez Corcoles JA (Palma de Mallorca, Spain); Rodicio

Miravalles JL, Pais SA, Turienzo SA, Alvarez LS (Hospital Universitario Central de

Asturias, Spain); Campos PV, Rendo AG, García SS, Santos EPG (Hospital General

Universitario De Ciudad Real, Spain); Martínez ET, Fernández Díaz MJ, Magadán

Álvarez C (Hospital Universitario Marqués de Valdecilla, Spain); Concepción Martín

V, Díaz López C, Rosat Rodrigo A, Pérez Sánchez LE (Hospital Universitario

Nuestra Señora de Candelaria, Spain); Bailón Cuadrado M, Tinoco Carrasco C,

Choolani Bhojwani E, Sánchez DP (Hospital Universitario Río Hortega de Valladolid,

Spain); Ahmed ME (Shaab Teaching Hospital, Sudan); Dzhendov T (University

Hospital Linköping, Sweden); Lindberg F, Rutegård M (Umeå University Hospital,

Sweden); Sundbom M (Uppsala University Hospital, Sweden); Mickael C, Colucci N

(Geneva University Hospital, Switzerland); Schnider A (Triemli Hospital Zurich,

Switzerland); Er S (Ankara Numune Hospital, Turkey); Kurnaz E (Erzincan University

Hospital, Turkey); Turkyilmaz S, Turkyilmaz A, Yildirim R, Baki BE (Karadeniz

Technical University, Turkey); Akkapulu N (Hacettepe University Hospital, Turkey);

Karahan O, Damburaci N (Usak University Training and Research Hospital, Turkey);

Hardwick R, Safranek P, Sujendran V, Bennett J, Afzal Z (Addenbrooke's Hospital,

Cambridge, United Kingdom (UK)); Shrotri M, Chan B, Exarchou K, Gilbert T

(Aintree University Hospital, Liverpool, UK); Mukherjee S, Amalesh T (Barking

Havering and Redbridge NHS Trust, UK); Kennedy R, McCain S, Harris A, Dobson

G (Belfast City Hospital, UK); Davies N, Wilson I, Mayo D, Bennett D (Royal

Bournemouth Hospital, UK); Young R, Manby P (Bradford Royal Infirmary, UK);

Blencowe N, Schiller M, Byrne B (University Hospitals Bristol NHS Foundation Trust,

UK); Mitton D, Wong V, Elshaer A, Cowen M (Castle Hill Hospital, UK); Menon V,

Tan LC, McLaughlin E, Koshy R (University Hospital of Coventry, UK); Sharp C

(University Hospital Crosshouse, UK); Brewer H, Das N, Cox M, Al Khyatt W, Worku

D (Royal Derby Hospital, UK); Iqbal R, Walls L, McGregor R (Edinburgh Royal

Infirmary, UK); Fullarton G, Macdonald A, MacKay C, Craig C (Glasgow Royal

Infirmary, UK); Dwerryhouse S, Hornby S, Jaunoo S, Wadley M ( Gloucester Royal

Hospital, UK); Baker C, Saad M, Kelly M, Davies A, Di Maggio F (Guy's and St

Thomas's Hospitals, UK); McKay S, Mistry P, Singhal R, Tucker O, Kapoulas S,

Powell-Brett S (Heartlands Hospital, UK); Davis P, Bromley G, Watson L (James

Cook University Hospital, UK); Verma R, Ward J, Shetty V, Ball C, Pursnani K

(Lancashire Teaching Hospitals NHS Foundation Trust, UK); Sarela A, Sue Ling H,

Mehta S, Hayden J, To N (Leeds Teaching Hospitals NHS Trust, UK); Palser T,

Hunter D, Supramaniam K, Butt Z, Ahmed A (University Hospitals of Leicester NHS

Trust, UK); Kumar S, Chaudry A, Moussa O, Wiggins TH (Royal Marsden Hospital,

UK); Wilson M, Patil P, Noaman I (Ninewells Hospital, UK); Willem J (Norfolk and

Norwich University Hospital); Bouras G, Evans R, Singh M, Warrilow H, Ahmad A

(University Hospital of North Midlands, UK); Tewari N, Yanni F, Couch J,

Theophilidou E, Reilly JJ, Singh P (Nottingham University Hospital, UK); van Boxel

Gijs, Akbari K, Zanotti D, Sgromo B (Oxford University Hospitals); Sanders G,

Wheatley T, Ariyarathenam A, Reece-Smith A, Humphreys L (Plymouth Hospitals

NHS Trust, UK); Choh C, Carter N, Knight B, Pucher P (Queen Alexandra Hospital,

Portsmouth, UK); Athanasiou A, Mohamed I, Tan B, Abdulrahman M (Queen

Elizabeth Hospital Birmingham, UK); Vickers J, Akhtar K, Chaparala R, Brown R,

Alasmar MMA (Salford Royal Foundation Trust, UK); Ackroyd R, Patel K, Tamhankar

A, Wyman A (Sheffield Teaching Hospitals NHS Foundation Trust, UK); Walker R,

Grace B (University Hospital Southampton NHS Foundation Trust, UK); Abbassi N,

Slim N, Ioannidi L (University College Hospital, UK); Blackshaw G, Havard T,

Escofet X, Powell A (University Hospital of Wales, UK); Owera A, Rashid F,

Jambulingam P, Padickakudi J (Watford General Hospital, UK); Ben-Younes H,

Mccormack K (University Hospital Wishaw, UK); Makey IA (Mayo Clinic in Florida,

United States of America (USA)); Karush MK, Seder CW, Liptay MJ, Chmielewski G

(Rush University Medical Center, USA); Rosato EL, Berger AC, Zheng R, Okolo E

(Thomas Jefferson University, USA); Singh A, Scott CD, Weyant MJ, Mitchell JD

(University of Colorado Hospital, USA).