Hospital and surgeon volume in relation to long-term survival after oesophagectomy : systematic review and meta-analysis







Full text



Hospital and surgeon volume in relation to

long-term survival after oesophagectomy: systematic

review and meta-analysis

Nele Brusselaers,


Fredrik Mattsson,


Jesper Lagergren

1,2 ▸ Additional material is

published online only. To view please visit the journal online ( gutjnl-2013-306074). 1Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden 2

Division of Cancer Studies, King’s College London, General Surgery Offices, St Thomas’ Hospital, London, UK Correspondence to Dr Nele Brusselaers, Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Norra Stationsgatan 67, Level 2, Karolinska Institutet, Stockholm SE-171 76, Sweden; Received 11 September 2013 Revised 30 October 2013 Accepted 10 November 2013 To cite: Brusselaers N, Mattsson F, Lagergren J. Gut Published Online First: [ please include Day Month Year] doi:10.1136/gutjnl-2013-306074


Background Centralisation of healthcare, especially for advanced cancer surgery, has been a matter of debate. Clear short-term mortality benefits have been described for oesophageal cancer surgery conducted at high-volume hospitals and by high-high-volume surgeons. Objective To clarify the association between hospital volume, surgeon volume and hospital type in relation to long-term survival after oesophagectomy for cancer, by a meta-analysis.

Design The systematic literature search included PubMed, Web of Science, Cochrane library, EMBASE and Science Citation Index, for the period 1990–2013. Eligible articles were those which reported survival (time to death) as HRs after oesophagectomy for cancer by hospital volume, surgeon volume or hospital type. Fully adjusted HRs for the longest follow-up were the main outcomes. Results were pooled by a meta-analysis, and reported as HRs and 95% CIs.

Results Sixteen studies from seven countries met the inclusion criteria. These studies reported hospital volume (N=13), surgeon volume (N=4) or hospital type (N=4). A survival benefit was found for high-volume hospitals (HR=0.82, 95% CI 0.75 to 0.90), and possibly also, for high-volume surgeons (HR=0.87, 95% CI 0.74 to 1.02) compared with their low-volume counterparts. No association with survival remained for hospital volume after adjustment for surgeon volume (HR=1.01, 95% CI 0.97 to 1.06; N=2), while a survival benefit was found in favour of high-volume surgeons after adjustment for hospital volume (HR=0.91, 95% CI 0.85 to 0.98; N=2). Conclusions This meta-analysis demonstrated better long-term survival (even after excluding early deaths) after oesophagectomy with high-volume surgery, and surgeon volume might be more important than hospital volume. Thesefindings support centralisation with fewer surgeons working at large centres.


Centralisation of complex cancer surgery is a topic of debate in several countries. Such centralisation can improve care by collating multidisciplinary expertise and experience, as well as specialised equipment, within centres of excellence, and will affect the healthcare budget. Treating more patients should improve the skills of the medical team, and

adapting specific treatment procedures should

facilitate and improve patient-tailored care.

However, the benefit of such centralisation should be weighed up against the potential disadvantages for patients— for example, long travel times and

social isolation.1Oesophageal cancer surgery is one of the most complex surgical procedures, entailing a substantial risk of severe postoperative complica-tions, and a convincing benefit of centralisation has been shown for short-term mortality (in-hospital and 30-day postoperatively) for this operation.2–7 However, the existing data describing oesophageal cancer surgery volume in relation to long-term sur-vival are limited, and the results from individual studies are contradictory.7Moreover, the influence of tumour stage has not always been taken into


ficance of this study

What is already known about this subject?

▸ Oesophageal cancer has a very poor prognosis,

with a 5-year survival of only 30% after complete oesophageal cancer resection (oesophagectomy).

▸ Oesophagectomy is one of the most complex surgical procedures, entailing a substantial risk of severe postoperative complications. ▸ Short-term mortality (in-hospital and 30-day

postoperatively) has been shown to be lower if operations are carried out in high-volume hospitals and/or by high-volume surgeons. Yet, 95% of all patients survive thefirst 30 days after surgery.

▸ Based on these differences in short-term mortality, centralisation of oesophagectomy within centres of excellence has been

recommended and adopted in many countries.

What are the new


▸ This meta-analysis demonstrated a better long-term survival after oesophagectomy with high-volume surgery.

▸ Surgeon volume seems to be more important than hospital volume.

How might it impact on clinical practice in

the foreseeable future?

▸ Differences in long-term survival imply an ever greater benefit of centralisation for the number of patient-years than already presumed based on short-term mortality, since the mortality followed by such surgery is strongly dominated by deaths from tumour recurrence rather than procedure-related complications.


account in previous research, which is of major concern when-ever long-term mortality is the outcome. Thus, the impact of surgery volume on long-term survival after oesophageal cancer remains to be established. Such knowledge would be of clinical importance since tumour recurrence in oesophageal cancer is common, resulting in a risk of death of about 60–70% within 5 years of surgery.8 9The objective of this study was to clarify

the association between hospital volume, surgeon volume and hospital type in relation to long-term survival after oesophagect-omy for cancer, by means of a meta-analysis.


This was a systematic review and meta-analysis analysing differ-ences in long-term survival between high-volume and low-volume hospitals and surgeons after oesophagectomy for cancer. The available literature was identified and examined by a sys-tematic review and survival meta-analysis. The results are reported in accordance with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).10

The study followed an a priori established study protocol. Exposure and outcome

The main exposure was surgery performed in either low- or high-volume hospitals, as defined by the authors of the included studies. Other examined exposures were surgeon volume (low or high) and type of hospital (eg, university or non-university). Both surgeon and hospital volume were measured as the average annual number of oesophagectomies per year (eg, >10 or <10 procedures/year). The group with the lowest volume or non-university was used as reference category. If an included study reported HRs for different surgical volume groups, only the lowest and highest volume group were compared and reported in the Forest plots.

The study outcome was the time to death after the oesopha-gectomy, defined by a minimal period of follow-up of the study cohort of 3 months.

Data sources and searches

The primary data sources screened were PubMed and the Web of Science. The search string in these databases consisted of four parts: (1) the anatomical location of interest (ie, oesophagus, oesophagectomy, and oesophageal), (2) surgery, surgical or cancer, (3) outcome, mortality, survival or prognosis and (4) volume, determinants or predictors. Different spelling was accounted for, and medical subheadings (MeSH) were incorpo-rated in the PubMed search. Complementary searches were performed through analyses of reference lists, the Science Citation index, Cochrane library, EMBASE and searching for relevant publications of‘expert’ authors (known or identified to have published in thefield of surgery volume).

Study selection

The time period for publications was limited to January 1990 September 2013, a period which we considered to represent modern oesophageal cancer management. The search method used to identify all relevant articles was discussed and developed

by two authors (NB and JL) and the final search string was

approved by all authors. The initial search was performed by one reviewer (NB), who eliminated clearly irrelevant articles based on the title and abstract as defined by the pre-set selection criteria. Thefinal selection of articles was made by mutual con-sideration of all authors, based on the reporting of all necessary data and in accordance with the predefined inclusion and exclu-sion criteria.

Inclusion and exclusion criteria

Studies that provided original data on survival of patients who underwent oesophagectomy for malignancy were included. Abstracts or other conference proceedings, case reports, case series, intervention studies and review articles were excluded. Both prospective and retrospective studies were eligible. Articles describing oesophagectomy for non-malignant reasons were excluded, as were studies reporting a subgroup of oesophagect-omy patients only. If studies also reported survival after gastric cancer surgery, survival for oesophageal cancer had to be reported separately, otherwise the study was excluded. Language restriction was applied only in the end stage of the search, to enable assessment of language selection bias. The languages selected a priori as eligible were English, French, Dutch, German, Spanish, Swedish and Chinese. Studies were eligible only if HRs comparing survival after oesophagectomy by hos-pital or surgeon volume groups, or by hoshos-pital type were reported. The minimum reported follow-up time was 3 months. Data extraction and quality assessment

The following data were collected (if available): study and popu-lation characteristics, type of surgery and hospital characteristics. Assessment of quality and generalisability was based on the key domains considered fundamental for observational studies.11 From each article, the crude HRs were extracted (if reported), and the HRs based on the most fully adjusted regression models for the longest duration of follow-up. If several volume groups were reported, the most extreme comparison —that is, highest versus lowest reported volume, was considered the primary result. If possible, the HR for hospital volume adjusted for surgeon volume was extracted as well as the most fully adjusted model without adjustment for surgeon volume. The same approach was taken for surgeon volume and adjustment for hos-pital volume. If HRs were reported including and excluding ‘early’ mortality, defined as within 3 months of surgery, both HRs were extracted, but the HR including the full follow-up period was considered the main result.

Data synthesis and analysis

This survival meta-analysis pooled the HRs based on hospital volume, surgeon volume and hospital type. Subanalysis was based on duration of follow-up, inclusion or exclusion of early mortality and reported regression models. Random-effect meta-analyses were performed with STATA (StataCorp, V.12·1/ MP4), and were based on the HRs and SEs. The values were reported by a Forest plot, and uncertainty about the pooled esti-mates was quantified by 95% CI. If no SE was reported, it was calculated based on the 95% CI, number of patients or reported p values.12 13 The presence of small study effects and

publica-tion bias was evaluated by funnel plots and Egge’s regression asymmetry analysis.14 Statistical heterogeneity was assessed by

means of Cochran’s Q test and I2test. I2represents the percent-age of variation attributable to heterogeneity, which is usually

categorised as low (25–50%), moderate (51–75%) or high



Description of the included studies

The search wasfinalised on 10 September 2013, and included a total of 2392 publications as shown in the online supplementary appendix. The search resulted in 16 eligible studies. Only one potentially eligible Japanese study was excluded because of the language restriction.16

The eligible studies were from the USA (N=4),1 17–19 Sweden

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Table 1 Study and population characteristics of all 16 included studies dealing with survival after oesophageal cancer surgery

Author Year Region Cohort

Study inclusion period Study duration, years Age, years Male, % Adeno-carcinoma, % Squamous cell

carcinoma, % Exposure Mortality Survival after Maximum follow-up time, years Hospitals, N Oesophagectomies, annual maximum per hospital Surgeons, N Oesophagectomies, annual maximal per surgeon

Coupland28 2013 England Population-based 2004–2008 5 nr 72* HV All cause Surgery >1 144 132 nr nr

Derogar20 2013 Sweden Population-based 1987–2005 15 Median


74 36 60 SV, HV All cause Surgery 23 nr ≥17 nr ≥10 Dikken (1)24 2012 Netherlands Population-based 1989–2009 21 nr 76 75 23 HV All cause Diagnosis 3 44 >20 nr nr

Dikken (2)25 2012 Netherlands Population-based 1989–2009 21 nr 76 75 23 HT All cause Diagnosis 3 44 >20 nr nr

van de Poll-Franse26

2011 South Netherlands Population-based 1995–2006 12 Median 66

73–75 66–71 22–29 HV All cause Diagnosis 3 >12 15–20 nr 15–20 Cheung19 2010 Florida, USA Population-based 1998–2002 5 Median

69† 75† 48† 45† HT All cause nr 12? nr nr nr nr Stavrou29 2010 New S-Wales, Australia Population-based 2000–2005 6 nr 74 nr nr HV From cancer Diagnosis 3 nr >20 nr nr

Bilimoria1 2008 USA Population-based 1994–1999 6 Median


nr nr nr HV All cause Surgery 5 1154 >15 nr nr

Sundelof22 2008 Sweden Population-based 1994–1997 4 nr 83 nr nr SV, HV All cause Surgery 5 33 ≥10 nr ≥10

Birkmeyer17 2007 USA Hospital/

NCI-centre based

1992–2002 11 nr 74–79 nr nr HV All cause Surgery 5 206 107 nr nr Ioka31 2007 Osaka, Japan Population-based 1994–1998 5 nr nr nr nr HV All cause Diagnosis 5 143 >43 nr nr

Rouvelas21 2007 Sweden Population-based 1987–2000 14 Mean


71–72 26–29 59–66 HV All cause Surgery 5 22–30 ≥10 nr nr Simunovic30 2006 Ontario, Canada Population-based 1990–2000 11 Median


nr nr nr HV, HT All cause Admission for surgery

10? 68 ≥44 nr nr

Birkmeyer18 2005 USA Hospital/

NCI-centre based

1994–1999 6 nr 75–77 nr nr HT All cause Surgery 5 102 107 nr nr Wenner23 2005 Sweden Population-based 1987–1996 10 Median

66–67† 75– 77†

77† 23† HV All cause Surgery 5 74 >20 nr 34 Bachmann27 2002 South and West


Hospital-based 1996–1997 1 nr nr nr nr SV, HV All cause Surgery 3 23 83 nr nr *Also including patients with gastric carcinoma.

†Also including non-operated patients.

HT, hospital type; HV, hospital volume; nr, not reported; SV, surgeon volume .

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(N=4),20–23 the Netherlands (N=3),24–26 the UK (N=2),27 28

Australia (N=1),29Canada (N=1)30and Japan (N=1).31The longest reported follow-up was 23 years.20Thirteen studies reported HRs

for survival by hospital volume groups (n=39 761),1 17 20–24 26–31 four by surgeon volume (n=2874),20 22 26 27and four by hospital

type (n=13 433).18 19 25 26Two of the three Dutch studies described the same nationwide cohort, once for hospital volume and once for hospital type,24 25 and there was some overlap with the third (regional) study.26 The studies from the UK did not overlap.27 28

Some overlap was possible in the four American studies.1 17–19The study periods of the three oldest (nationwide) Swedish studies partly overlapped.21–23An overview of the main study characteristics is pre-sented in table 1, and a quality assessment is shown infigure 1. All but three studies17 18 27were population-based, and 10 studies were nationwide. Eight studies also described other cancer types. Mean or median age of patients undergoing the operation ranged from 63 to 66 years, as reported in four studies.1 20 21 30The proportion of male

patients, as reported in nine studies, ranged from 71% to 83%. Four studies reported the proportion of the main histological types: adeno-carcinoma (26–75%) and squamous cell carcinoma (22–66%).20 21

24 25

Hospital volume and long-term survival

All 13 studies dealing with hospital volume reported adjusted HRs. One study considered hospital volume as a continuous vari-able (HR for an increase of 10 oesophagectomies per year) and reported only HRs adjusted for surgeon volume.27Another study

reported HRs both including and excluding adjustment for surgeon volume.20Ten studies reported HRs for the complete

sur-vival period, two of which also reported HRs excluding mortality within thefirst 2 months of surgery,1or as‘survived surgery’ (not

specified).17Three studies reported only HRs excluding early mor-tality— that is, the first 2,233,20or 624postoperative months.20

Six studies adjusted for tumour stage.1 17 20 22 24 31

The pooled adjusted HRs of mortality in 12 studies (exclud-ing the study adjust(exclud-ing for surgeon volume)27was 0.82 (95% CI 0.75 to 0.90) in favour of high-volume hospitals (figure 2). The statistical heterogeneity was moderate (I2=68.0%). Subanalyses are presented in table 2, showing a pooled HR of 0.76 (95% CI 0.68 to 0.84) in studies adjusting for tumour stage. The seven

studies with the longest complete follow-up (over 3 years) showed an HR of 0.77 (95% CI 0.69 to 0.87), and a survival benefit remained after exclusion of early mortality (HR=0.85, 95% CI 0.75 to 0.95) (table 2). In the two studies reporting complete follow-up, and follow-up without early mortality,1 17

the HRs were 0.75 (95% CI 0.69 to 0.81) and 0.78 (95% CI 0.71 to 0.85), respectively, and I2=0%. In the two studies that

adjusted for surgeon volume, the HR was 1.01 (95% CI 0.97 to 1.06, I2=0%) (figure 2).

There was no evidence of publication bias or small-study effects bias ( p=0.313) (funnel plot not shown).

Surgeon-volume and long-term survival

The four studies that reported HRs for surgeon volume also reported hospital volume.20 22 26 27In one study, surgeon and hospital volume were equivalent since all oesophagectomies were performed by one surgical team led by one surgeon at each specialised regional centre.26 One study reported the HR for surgeon volume adjusted for hospital volume as a continu-ous variable.27 Another study reported HRs with and without adjustment for hospital volume.20One study reported both hos-pital and surgeon volume, but did not conduct any mutual adjustment for these variables.22Only one study excluded early mortality (within 3 months of surgery).20 The follow-up time ranged from 2 to 23 years.20 22 26 27Only two studies adjusted for tumour stage.20 22

As presented infigure 3, the pooled adjusted HR for surgeon volume was 0.87 (95% CI 0.74 to 1.02) in favour of high surgeon volumes. After further adjustment for hospital volume, the pooled HR was 0.91 (95% CI 0.85 to 0.98). Statistical het-erogeneity in both analyses was low (I2=0%).

There was no evidence of publication bias or small-study effects bias ( p=0.150) (funnel plot not shown).

Hospital type and long-term survival

Four studies analysed hospital type in relation to survival after oesophagectomy.18 19 25 26 It was not possible to calculate a pooled HR because of clinical heterogeneity between these studies (figure 4).

Figure 1 Characteristics and quality assessment of all 16 included studies dealing with survival after oesophageal cancer surgery.

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This meta-analysis indicates a survival benefit in favour of high-volume hospitals and high-high-volume surgeons compared with the

low-volume equivalents. No independent risk reduction

remained for high hospital volume after adjustment for surgeon

volume, while high surgeon volume remained beneficial after

adjustment for hospital volume.

Strengths of meta-analyses include the fact that they facilitate objective evaluation and pooling of different study populations, enable analyses of large and diverse cohorts of patients and

summarise the available evidence up to a certain time. Inherent limitations of meta-analyses are that the results depend on the availability, quality and methods of the published studies, and they might be hampered by publication bias and clinical and statistical heterogeneity. However, there was no evidence of pub-lication bias in this study, and the statistical heterogeneity was low to moderate. Language bias cannot be ruled out completely since we based our search on English-language dominated sources. Only one potentially eligible study was excluded because of the language,16 but this Japanese study was con-ducted by the same group as in an included study.31Moreover,

even after implementing strict inclusion criteria, a considerable clinical heterogeneity remained between study populations. Moreover, meta-analyses assessing long-term survival are more complex than those evaluating short-term mortality, because of the need to take duration of survival and variation in follow-up time into account.

Despite the heterogeneity between studies, this study provides evidence of improved long-term survival when the oesophagect-omy is conducted at high-volume hospitals and by high-volume surgeons. This distinction between early mortality and long-term mortality enables comparison of the underlying mechan-isms; when patients die early after surgery it is usually owing to complications, while later deaths are typically related to cancer recurrence. This study showed that even after excluding thefirst months after surgery, a 15% benefit in favour of high-volume hospitals remained, indicating that surgery volume influences the risk of tumour recurrence. Thesefindings support centralisa-tion of oesophageal cancer surgery to fewer surgeons working at centres of excellence in this field.32–34 The discussion about which hospital and surgeon volume should be recommended cannot be answered by this study. As in other meta-analyses2 6 Figure 2 Forrest plot of survival benefit based on annual hospital volume of oesophageal cancer surgery, in 13 studies. The adjusted HRs are based on the most fully adjusted models as reported for each study, excluding or including adjustment for surgeon volume. ¤Hospital volume was reported as average per quartile (range per quartile not reported). *Hospital volume was considered a continuous variable and HRs were reported for an increase of 10 units.

Table 2 Subanalyses for survival by hospital volume of the 12 studies reporting HRs without adjustment for surgeon volume of oesophageal cancer surgery

Hospital volume (N=12) HR 95% CI N studies I2

All 0.82 0.75 to 0.90 12 68.0

Adjusted for tumour stage 0.76 0.68 to 0.84 6 67.0 Not adjusted for tumour stage 0.91 0.83 to 1.00 6 11.8 Early mortality excluded 0.85 0.75 to 0.95 5 68.3 Complete follow-up* 0.78 0.70 to 0.87 9 61.4 Long follow-up (>3 years) 0.80 0.71 to 0.89 8 70.1 Long and complete follow-up (>3 years)* 0.77 0.69 to 0.87 7 67.1 Short follow-up (max 3 years) 0.90 0.72 to 1.14 4 71.4 Short and complete follow-up

(max 3 years)*

0.97 0.55 to 1.73 2 50.1

*Complete follow-up includes only studies reporting survival including mortality within the early postoperative period.

Values are presented as pooled HRs and 95% CIs, with low-volume hospital groups as reference category. The I2represents the percentage of variation attributable to


we compared the largest volume group with the lowest volume group when different thresholds were used, so based on this

study design we cannot define a recommended quantity of

annual oesophagectomies by hospital or surgeon.

Thefindings of this study complement previous meta-analyses evaluating short-term mortality after oesophagectomy, with

pooled ORs of 0.20–0.40 for high-volume hospitals compared

with low-volume hospitals.2 4 6 35 However, deaths from

tumour recurrence after oesophageal cancer surgery are far

more common (60–70%) than deaths occurring during the

initial postoperative period (<5%), emphasising the relevance of evaluating surgery volume in relation to longer-term survival.

Yet, this issue has been dealt with in only a few systematic reviews,4 6 36–38 and one meta-analysis based on four studies.6 The previous meta-analysis showed an OR of survival of 1.17 (95% CI 1.05 to 1.31) in favour of high-volume hospitals, but it did not take the time to death into account.6Nevertheless, the

finding of that meta-analysis is in line with the results of our study.

An important, yet complex, question is the underlying mech-anism of thefindings of this study, and if hospital and surgeon volumes should be considered separate entities or merely proxies of each other. The surgery volume effect might be due to the total package of multidisciplinary teams, advanced Figure 3 Forrest plot of survival benefit based on annual surgeon volume of oesophageal cancer surgery, based on four studies. The adjusted HRs are based on the most fully adjusted models as reported for each study, excluding or including adjustment for hospital volume. *Surgeon volume was considered a continuous variable and HRs were reported for an increase of 10 units.

Figure 4 Forrest plot of survival benefit of hospital type of oesophageal cancer surgery, based on four studies. The adjusted HRs are based on the most fully adjusted models as reported for each study. AdenoCa, adenocarcinoma; NCI, National Cancer Institute (USA); SCC, squamous cell carcinoma. University and teaching hospitals were assumed to have a higher volume than non-university and non-teaching hospitals; NCI hospitals had similar hospital volumes to the control hospitals.

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diagnostics, treatment and care, or alternatively, it might mainly be due to the experience and expertise of the surgeon and the surgical team. This study found no association between hospital volume and survival when considering only the two studies adjusting for surgeon volume, but interestingly, the influence of surgeon volume remained after adjusting for hospital volume. Although based on a small number of studies, this might suggest a more important role for surgeon volume than hospital volume.

It is important to point out that survival depends not only on surgery volume.39Substantial logistical and case-mix differences

exist between countries, especially for geographical distances and tumour incidence. A related question is if the patient popu-lation and case-mix, particularly for tumour stage and socio-economic status, are similar between volume groups.40 41In an

attempt to adjust for such confounding, we included only the most fully adjusted regression models. The six studies including adjustment for tumour stage, the strongest prognostic factor, showed a larger effect than those which did not adjust (24% vs 9%), which indicates robustness of thefindings of this study.

The size of the effect of high surgery volume in relation to long-term survival after oesophageal cancer surgery is not negli-gible. The effect size is similar to the effect of preoperative oncological therapy that has been demonstrated in recent large meta-analyses,42and neoadjuvant therapy has therefore become

routine clinical practice for these patients in most countries. It therefore seems logical that centralisation of this surgery should be a prioritised measure to improve the prognosis in oesopha-geal cancer.

To conclude, this meta-analysis of long-term survival after

oesophageal cancer surgery showed an 18–25% and 9–13%

improved survival for high-volume hospitals and high-volume surgeons, respectively, compared with their low-volume counter-parts. This difference in survival was not solely due to a decreased early postoperative mortality, since even after exclu-sion of early deaths, a 15% benefit was found. Surgeon volume appears to be more strongly related to survival than hospital volume.

Contributors All three authors contributed to the conception and design of the study. NB and FM performed the analysis and interpreted the data. NB drafted the article, which was revised critically for important intellectual content by all authors. All authors approved thefinal version of the manuscript.

Funding This study was funded by the Swedish Research Council (SIMSAM): 2008– 7496, and Swedish Cancer Society (grant number 120748).

Competing interests None.

Provenance and peer review Not commissioned; externally peer reviewed. Data sharing statement All data are presented in the article.


1 Bilimoria KY, Bentrem DJ, Feinglass JM, et al. Directing surgical quality improvement initiatives: comparison of perioperative mortality and long-term survival for cancer surgery. J Clin Oncol 2008;26:4626–33.

2 Markar SR, Karthikesalingam A, Thrumurthy S, et al. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000– 2011. J Gastrointest Surg 2012;16:1055–63.

3 Lauder CI, Marlow NE, Maddern GJ, et al. Systematic review of the impact of volume of oesophagectomy on patient outcome. ANZ J Surg 2010;80:317–23. 4 Gruen RL, Pitt V, Green S, et al. The effect of provider case volume on cancer

mortality: systematic review and meta-analysis. CA Cancer J Clin 2009;59:192–211. 5 Tol JA, van Gulik TM, Busch OR, et al. Centralization of highly complex low-volume procedures in upper gastrointestinal surgery. A summary of systematic reviews and meta-analyses. Dig Surg 2012;29:374–83.

6 Wouters MW, Gooiker GA, van Sandick JW, et al. The volume-outcome relation in the surgical treatment of esophageal cancer: a systematic review and meta-analysis. Cancer 2012;118:1754–63.

7 Lagergren J, Lagergren P. Recent developments in esophageal adenocarcinoma. CA Cancer J Clin 2013;63:232–48.

8 Rutegard M, Charonis K, Lu Y, et al. Population-based esophageal cancer survival after resection without neoadjuvant therapy: An update. Surgery 2012;152:903–10. 9 Koppert LB, Lemmens VE, Coebergh JW, et al. Impact of age and co-morbidity on

surgical resection rate and survival in patients with oesophageal and gastric cancer. Br J Surg 2012;99:1693–700.

10 Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine 2009;6:e1000097. doi:10/1371/journal.pmed.1000097

11 Sanderson S, Tatt ID, Higgins JP. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol 2007;36:666–76.

12 Michiels S, Piedbois P, Burdett S, et al. Meta-analysis when only the median survival times are known: a comparison with individual patient data results. Int J Technol Assess Health Care 2005;21:119–25.

13 Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998;17:2815–34. 14 Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a

simple, graphical test. BMJ 1997;315:629–34.

15 Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.

16 Hattori M, Fujita M, Nakamura Y, et al. [Estimation of the effects of centralization of cancer treatment on mortality reduction by in Fukui Prefecture]. Nihon Koshu Eisei Zasshi 2010;57:263–70.

17 Birkmeyer JD, Sun Y, Wong SL, et al. Hospital volume and late survival after cancer surgery. Ann Surg 2007;245:777–83.

18 Birkmeyer NJ, Goodney PP, Stukel TA, et al. Do cancer centers designated by the National Cancer Institute have better surgical outcomes? Cancer 2005;103:435–41. 19 Cheung MC, Koniaris LG, Yang R, et al. Do all patients with carcinoma of the

esophagus benefit from treatment at teaching facilities? J Surg Oncol 2010;102:18–26.

20 Derogar M, Sadr-Azodi O, Johar A, et al. Hospital and surgeon volume in relation to survival after esophageal cancer surgery in a population-based study. J Clin Oncol 2013;31:551–7.

21 Rouvelas I, Lindblad M, Zeng W, et al. Impact of hospital volume on long-term survival after esophageal cancer surgery. Arch Surg 2007;142:113–17; discussion 8. 22 Sundelof M, Lagergren J, Ye W. Surgical factors influencing outcomes in patients

resected for cancer of the esophagus or gastric cardia. World J Surg 2008;32:2357–65.

23 Wenner J, Zilling T, Bladstrom A, et al. The influence of surgical volume on hospital mortality and 5-year survival for carcinoma of the oesophagus and gastric cardia. Anticancer Res 2005;25:419–24.

24 Dikken JL, Dassen AE, Lemmens VE, et al. Effect of hospital volume on postoperative mortality and survival after oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009. Eur J Cancer 2012;48:1004–13. 25 Dikken JL, Wouters MW, Lemmens VE, et al. Influence of hospital type on outcomes

after oesophageal and gastric cancer surgery. Br J Surg 2012;99:954–63. 26 van de Poll-Franse LV, Lemmens VE, Roukema JA, et al. Impact of concentration of

oesophageal and gastric cardia cancer surgery on long-term population-based survival. Br J Surg 2011;98:956–63.

27 Bachmann MO, Alderson D, Edwards D, et al. Cohort study in South and West England of the influence of specialization on the management and outcome of patients with oesophageal and gastric cancers. Br J Surg 2002;89:914–22. 28 Coupland VH, Lagergren J, Luchtenborg M, et al. Hospital volume, proportion

resected and mortality from oesophageal and gastric cancer: a population-based study in England, 2004–2008. Gut 2013;62:961–6.

29 Stavrou EP, Smith GS, Baker DF. Surgical outcomes associated with oesophagectomy in New South Wales: an investigation of hospital volume. J Gastrointest Surg 2010;14:951–7.

30 Simunovic M, Rempel E, Theriault ME, et al. Influence of hospital characteristics on operative death and survival of patients after major cancer surgery in Ontario. Can J Surg 2006;49:251–8.

31 Ioka A, Tsukuma H, Ajiki W, et al. Hospital procedure volume and survival of cancer patients in Osaka, Japan: a population-based study with latest cases. Jpn J Clin Oncol 2007;37:544–53.

32 Chang KH, McAnena OJ, Smith MJ, et al. Surgery for oesophageal cancer at Galway University Hospital 1993–2008. Ir J Med Sci 2010;179:521–7. 33 Forshaw MJ, Gossage JA, Stephens J, et al. Centralisation of oesophagogastric

cancer services: can specialist units deliver? Ann R Coll Surg Engl 2006;88:566–70. 34 Wouters MW, Karim-Kos HE, le Cessie S, et al. Centralization of esophageal cancer

surgery: does it improve clinical outcome? Ann Surg Oncol 2009;16:1789–98. 35 Metzger R, Bollschweiler E, Vallbohmer D, et al. High volume centers for

esophagectomy: what is the number needed to achieve low postoperative mortality? Dis Esophagus 2004;17:310–14.

36 Wouters MW, Krijnen P, Le Cessie S, et al. Volume- or outcome-based referral to improve quality of care for esophageal cancer surgery in The Netherlands. J Surg Oncol 2009;99:481–7.


37 Killeen SD, O’Sullivan MJ, Coffey JC, et al. Provider volume and outcomes for oncological procedures. Br J Surg 2005;92:389–402.

38 Holscher AH, Metzger R, Brabender J, et al. High-volume centers–effect of case load on outcome in cancer surgery. Onkologie 2004;27:412–16.

39 Meguid RA, Weiss ES, Chang DC, et al. The effect of volume on esophageal cancer resections: what constitutes acceptable resection volumes for centers of excellence? J Thorac Cardiovasc Surg 2009;137:23–9.

40 Boudourakis LD, Wang TS, Roman SA, et al. Evolution of the surgeon-volume, patient-outcome relationship. Ann Surg 2009;250:159–65.

41 Wouters MW, Wijnhoven BP, Karim-Kos HE, et al. High-volume versus low-volume for esophageal resections for cancer: the essential role of case-mix adjustments based on clinical data. Ann Surg Oncol 2008;15:80–7. 42 Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant

chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 2011;12:681–92.

8 Brusselaers N, et al. Gut 2013;0:1–8. doi:10.1136/gutjnl-2013-306074


on November 24, 2013 - Published by


doi: 10.1136/gutjnl-2013-306074

published online November 22, 2013


Nele Brusselaers, Fredrik Mattsson and Jesper Lagergren

systematic review and meta-analysis

long-term survival after oesophagectomy:

Hospital and surgeon volume in relation to

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