Asian Journal of Surgery (2012) 35, 104e109

Available online at www.sciencedirect.com

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ORIGINAL ARTICLE

Prediction of major postoperative complications

and survival for locally advanced esophageal
carcinoma patients
Somkiat Sunpaweravong a,*, Sakchai Ruangsin a,
Supparerk Laohawiriyakamol a, Somrit Mahattanobon a, Alan Geater b

a
Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
b
Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand

Received 3 March 2011; received in revised form 21 June 2011; accepted 17 April 2012
Available online 6 June 2012

KEYWORDS Summary Background: Predicting the major complications after esophagectomy is impor-
complication; tant and may help in preselecting patients who are most likely to benefit from surgery, espe-
esophagectomy; cially in locally advanced esophageal cancer patients who have poor prognosis.
leak; Objective: To identify the factors associated with the development of pneumonia and anasto-
pneumonia; motic leakage complications, and the survival characteristics in locally advanced esophageal
survival cancer patients.
Methods: A consecutive series of 232 locally advanced esophageal cancer patients (183 men
and 49 women, median age 63 years) who underwent esophagectomy at Prince of Songkla
University Hospital between 1998 and 2007 was analyzed.
Results: There were nine (3.8%) 30-day mortalities. Pneumonia occurred in 53 patients (22.8%)
and anastomotic leakage in 37 patients (15.9%). Multivariate analyses showed that low body mass
index was related to leakage (p Z 0.015), while soft-diet dysphagia (p Z 0.009), forced expira-
tory volume in 1 second <75% (p Z 0.0005), type of surgery (McKeown technique) (p Z 0.019),
and long operative time (p Z 0.006) were related to pneumonia. The median survival rate was
13.0 months. Stage 2b patients had longer survival than stages 3 and 4a patients (p Z 0.0001).
Conclusion: Patient body mass index, dysphagia, spirometry, type of surgical technique, and
operative time can help predict the likelihood of pulmonary or leak complications after esopha-
gectomy. TNM (Tumor, Node, Metastasis) staging can help predict the overall survival after resec-
tion in locally advanced cases.
Copyright ª 2012, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights
reserved.

* Corresponding author. Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkla 90110, Thailand.
E-mail address: susomkia@medicine.psu.ac.th (S. Sunpaweravong).

1015-9584/$36 Copyright ª 2012, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.
doi:10.1016/j.asjsur.2012.04.029
Complications and survival for esophagectomy 105

1. Introduction Table 1 Distributions of patient variables and univariate

analysis of anastomotic leak and pneumonia complications.
Esophageal carcinoma is the eighth most common cancer Variable Number Leak p Pneumonia p
and the sixth most frequent cause of cancer deaths
worldwide.1 Surgical techniques and multimodality treat- Total 232 37 53
ments have improved over the years; however, improved (100%) (15.9%) (22.8%)
rates of postoperative complications and survival after Age (y)
esophagectomy have not followed the treatment improve- <60 84 13 0.76 18 0.49
ments, especially in locally advanced stages. The more 60e70 75 13 18
common major postoperative complications of esophageal >70 73 11 17
carcinoma include pneumonia and anastomotic leakage, Sex
both of which are correlated with mortality. TNM (Tumor, Male 183 30 0.72 45 0.22
Node, Metastasis) staging has long served as the best tool to Female 49 7 8
predict survival, but this system is based solely on the
anatomic extent of invasion and metastasis and does not Soft-diet dysphagia
incorporate noncarcinoma variables such as patient char- Yes 210 35 0.65 52 0.004
acteristics, concomitant illnesses, or treatment.2 No 22 2 1
The aim of this study was to assess the prediction of Weight loss
10%
postoperative esophagectomy pneumonia, anastomotic Yes 130 21 0.92 30 0.92
leakage complications, and survival characteristics in No 102 16 23
locally advanced esophageal cancer patients.
BMI (kg/m2)
<17 64 18 0.02 14 0.76
2. Patients and methods 17e20 90 12 19
>20 78 7 20
The study was approved by the ethics committee of the
Tumor location
Faculty of Medicine of Prince of Songkla University.
Upper 24 2 0.68 3 0.44
Prospective data from 232 consecutive patients with Tany
Middle 115 18 31
to operable T4, N1, and M0/M1a who underwent surgical
Lower 93 17 19
resection for primary esophageal carcinoma at Prince of
Songkla University Hospital between January 1998 and Stage
December 2007 were collected, including patient charac- 2b 96 20 0.91 23 0.43
teristics, blood chemistry and lung function test results, 3 105 13 24
perioperative information, postoperative complications, 4a 31 4 6
and pathological findings.
FEV1 (%)
The preoperative evaluations included a precise history
<75 27 5 0.99 14 0.002
and physical examination. Staging was based on chest X-

75 174 29 33
ray, esophagogastroduodenoscopy with biopsy, bronchos-
*(sensor) (31) (3) (6)
copy, endoscopic ultrasound, and computed tomography
scans of chest and abdomen, and followed the sixth edition FVC (%)
of the American Joint Committee on Cancer TNM staging <75 32 7 0.54 15 0.005
system.3
75 169 27 33
In general, an IvoreLewis technique was performed for *(sensor) (31) (3) (5)
lower esophageal cancer and a McKeown technique for
Hct (%)
upper to lower parts. Two-field (mediastinal and abdominal
<35 92 15 0.73 26 0.23
stations) lymph node dissection was a routine procedure,
35e40 85 15 15
and three-field (cervical, mediastinal, and abdominal
>40 55 7 12
stations) lymph node dissection was performed when
cervical lymphadenopathy was found. A transhiatal or blunt Albumin (g/dL)
technique was usually performed in cases of patients with <3.5 57 10 0.92 15 0.77
a poor pulmonary function test. 3.5e4 79 12 17
Postoperative anastomotic leakage was defined as a leak >4 96 15 21
requiring surgical treatment or contrast study documenta-
FBS (mg/dL)
tion. Postoperative pneumonia was defined as a febrile
<100 97 15 0.79 24 0.12
illness plus the presence of pulmonary infiltration and
100e110 53 10 16
leukocytosis. Neoadjuvant chemoradiation (5-FU plus
>110 82 12 13
cisplatin) was given to patients with a clinical resectable
T4-tumor and adjuvant radiation or chemoradiation (5-FU Cr clearance
plus cisplatin) was given to patients following microscopic <50 101 16 0.96 23 0.98
residual (R1) or gross residual (R2) surgery. Patients were
50 131 21 30
followed at 3-month intervals in the 1st year and at 6-month
(continued on next page)
intervals in the 2nd and 3rd years, and then at 12-month
106 S. Sunpaweravong et al.

Table 1 (continued ) Table 3 Multivariate analysis of pneumonia.

Variable Number Leak p Pneumonia p Variable Odds ratio 95% CI p
Soft-diet dysphagia
Treatment
No 1 0.009
Surgery alone 132 26 0.19 34 0.14
Yes 6.810 1.532e30.261
Sx þ XRT  chemo 100 11 19
FEV1 (%)
Surgery
<75 1 0.0005
IvoreLewis 82 16 0.56 12 0.009

75 0.196 0.056e0.451
McKeown 101 16 33
Blunt 49 5 8 Surgery
IvoreLewis 1 0.019
Blood loss (mL)
McKeown 2.617 1.168e5.859
<500 151 22 0.10 34 0.87
Blunt 1.988 0.630e6.268
500e1000 59 8 13
>1000 22 7 6 Operative time (h)
<5 1 0.006
Operative time (h)
5e6.5 3.010 1.231e7.359
<5 82 15 0.75 9 0.006
>6.5 4.499 1.633e12.390
5e6.5 99 15 28
>6.5 51 7 16
FBS Z fasting blood sugar; Hct Z hematocrit; XRT Z
radiotherapy. 37 patients (15.9%), and surgical site infection in 29
patients (12.5%).
The univariate analyses of pneumonia and leakage are
shown in Table 1. Low body mass index (BMI) was the only
intervals. Overall survival was calculated from the day of
significant risk factor for leakage, while soft-diet
surgery.
dysphagia, forced expiratory volume in 1 second (FEV1)
<75%, forced vital capacity <75%, type of oper-
2.1. Statistical analysis ationdMcKeown technique, and long operative time were
all found to be significant risk factors for pneumonia. The
We used the chi-square test for categorical comparison data. multivariate analyses of pneumonia and leakage are shown
A p value of <0.05 was considered to indicate statistical in Tables 2 and 3, and it was found that low BMI was related
significance. All tests were two-tailed with a 95% confidence to leakage (p Z 0.015), while soft-diet dysphagia
interval (CI). Univariate and multivariate analysis were used. (p Z 0.009), FEV1 <75% (p Z 0.0005), type of oper-
Stata version 10 statistical software (Stata Corp, College ationdMcKeown technique (p Z 0.019), and long operative
Station, TX, USA) was used for all statistical analyses. time (p Z 0.006) were related to pneumonia.
Follow-up times ranged from 3 to 38 months, and the
median survival was 13.0 months (Fig. 1). The univariate
3. Results
analysis of survival at 1 year and 2 years is shown in Table 4.
Univariate and multivariate analyses revealed that only
A total of 232 patients were identified (183 men, 49
stage of disease was related to survival, as stage 2b had
women), with a median age of 63 years (range, 30e80). A
significantly better survival compared to stages 3 and 4a
total of 183 patients had a transthoracic resection (101
(p Z 0.0001) (Table 5). Stage-specific survivals are shown in
McKeown approaches and 82 IvoreLewis approaches), and
Fig. 2.
49 patients had a transhiatal resection. Moreover, 217
patients had squamous cell carcinoma and 15 patients had
adenocarcinoma. Of the 232 primary tumors studied, 94 4. Discussion
were classified as well, 97 as moderate, and 41 as poor
histologic differentiation. Esophagectomy has become the main treatment of esoph-
There were nine (3.8%) 30-day mortalities. The most ageal cancer even in the locally advanced stage. However,
frequent major morbidity was pneumonia, which occurred there are often serious postoperative complications such as
in 53 patients (22.8%), followed by anastomotic leakage in pneumonia and anastomotic leakage which increase the
risk of mortality.4,5
This study found post-esophagectomy pneumonia in
Table 2 Multivariate analysis of anastomotic leak. 22.8% of our patients, compared to rates in other studies
varying from 7.3% to 50%.6e11 Laws et al7 reported the
Variable Odds ratio 95% CI p incidence of major pulmonary complication to be 15.9%,
2
BMI (kg/m ) but these complications were responsible for 55% of patient
<17 1 0.015 deaths in their study. One study found that postoperative
17e20 0.651 0.572e2.949 pulmonary complications occurred more frequently after
>20 0.365 0.135e0.987 transthoracic esophagectomy than transhiatal esoph-
agectomy for esophageal cancer, and hypothesized that
Complications and survival for esophagectomy 107

pneumonia, and that the McKeown surgical approach took

Figure 1 KaplaneMeier analysis of overall survival.
this greater rate was because the thoracotomy procedure
itself tended to induce pulmonary complications.12 Unfor-
tunately, the perhaps less harmful transhiatal approach is
not suitable for curative surgery with lymph node dissec-
tion, so we performed this technique only in cases with
a poor pulmonary function test. We also found that long
operative time was related to post-esophagectomy
more time than the IvoreLewis and transhiatal approaches.
Preoperative spirometry should be done in every case
with a history of smoking or respiratory symptoms.13
Avendano et al14 reported that a preoperative FEV1 <65%
predicted was associated with an increased requirement
for respiration support during the postoperative period. We
found a forced vital capacity and an FEV1 <75% predicted
were related to postoperative pneumonia. We also found
that one of the predictors for pneumonia was soft-diet
dysphagia, which might have been associated with preop-
erative repeated aspirations leading to poor lung paren-
chyma. Lundy et al15 reported that aspiration was detected
by a modified barium swallow in 51.2% of their dysphagic
patients.
Anastomotic leakage is a major complication in esoph-
agectomy. Earlier studies have found an incidence of
leakage varying from 8% to 15% in general esophagec-
tomies, compared to 15.9% in this study, which focused on
the locally advanced stage.12 There are various causes of
such leakages, such as conduit ischemia, technical errors,
and malnutrition.16,17 Nutrition in patients with locally
advanced stage of disease may be compromised, especially
in cases of dysphagia, and correlated with an increased rate
of anastomotic leakage. Patil et al18 reported a correlation
between anastomotic leakage and an albumin level less
than 3 g/dL. We did not observe this association in our
patients; it may be that the preoperative serum albumin

Table 4 Distributions of patient variables and univariate analysis of survival at 1 year and 2 years.
Variable 1 y (%) 95% CI 2 y (%) 95% CI p
Age (y)
<60 48.91 38.38e58.62 23.91 15.79e32.99 0.06
60e70 51.39 39.34e62.18 25.00 15.72e35.39
>70 55.93 42.40e67.47 42.37 29.69e54.49
Sex
Male 49.71 42.11e56.85 26.86 20.53e33.57 0.20
Female 58.33 43.17e70.76 37.50 24.09e50.87
Soft-diet dysphagia
Yes 51.64 44.73e58.11 28.64 22.73e34.80 0.94
No 50.00 18.36e75.32 35.00 10.27e62.02
Weight loss
10%
Yes 50.82 41.64e59.27 26.23 18.80e34.25 0.37
No 52.48 42.32e61.66 32.67 23.77e41.86
BMI (kg/m2)
<17 48.33 35.28e60.21 20.00 11.04e30.88 0.12
17e20 51.72 40.78e61.60 29.89 20.67e39.64
>20 53.95 42.14e64.35 35.53 24.99e46.19
Tumor location
Upper 50.00 15.20e77.49 12.50 00.66e42.27 0.53
Middle 48.21 38.71e57.08 28.57 20.54e37.10
Lower 53.33 41.47e63.83 33.33 22.99e44.00
Tumor grading
Well 58.23 46.59e68.19 32.91 22.87e43.29 0.12
Moderate 31.25 16.38e47.34 21.88 09.65e37.24
Poor 54.76 43.54e64.66 32.14 22.48e42.18
(continued on next page)
108 S. Sunpaweravong et al.

Table 4 (continued )
Variable 1 y (%) 95% CI 2 y (%) 95% CI p
Cell type
Squamous CA 51.20 44.23e57.73 28.71 22.74e34.94 0.50
Adeno CA 63.64 29.69e84.52 36.36 11.18e62.68
Stage
2b 64.44 53.63e73.36 43.33 32.98e53.24 0.0004
3 42.42 32.61e51.89 19.19 12.14e27.47
4a 43.33 25.56e59.89 20.00 08.12e35.64
FEV1 (%)
<75 45.83 25.61e63.97 29.17 12.95e47.58 0.45

75 49.64 41.09e57.61 28.78 21.51e36.45
FVC (%)
<75 50.00 27.13e69.19 30.00 12.25e50.14 0.86

75 48.95 40.54e56.83 28.67 21.51e36.21
Treatment
Surgery alone 50.81 41.71e59.20 29.84 22.05e38.00 0.46
Sx þ XRT  chemo 51.61 41.04e61.19 26.88 18.35e36.14
Surgery
IvoreLewis 54.88 43.51e64.88 26.83 17.79e36.69 0.22
McKeown 53.06 42.73e62.35 35.71 26.38e45.14
Blunt 42.31 23.47e60.02 19.23 07.01e35.97
Blood loss (mL)
<500 52.38 44.01e60.08 27.89 20.91e35.29 0.97
500e1000 53.57 39.75e65.55 30.36 18.96e42.54
>1000 40.00 19.28e60.05 35.00 15.66e55.19
Operative time (h)
<5 52.50 41.05e62.73 28.75 19.32e38.86 0.88
5e6.5 50.53 40.10e60.05 28.42 19.76e37.67
>6.5 52.08 37.20e65.03 31.25 18.85e44.45

was not low because of dehydration. Our study also found esophageal resections for cancer were banned from hospi-
preoperative low BMI to be related to postoperative anas- tals with less than 10 procedures annually.27
tomotic leakage. This may be explained by the relation Chemoradiation followed by surgery is increasingly being
between low BMI and some degree of malnutrition from used in patients with locally advanced esophageal cancer.
dysphagia and cachexia. A meta-analysis from Graham et al28 showed that survival of
Mortality from esophagectomies has been steadily falling
over recent decades, and in most current studies it is
<5%.19e21 This improving outcome rate may result from
improvements in multidisciplinary pre- and postoperative
care, more refined patient selection, or the high-volume
center effect. Some studies have reported that doctor/
hospital volume was associated with better postoperative
mortality rates.22e25 Metzger et al26 found that institutions
with more than 20 procedures per year were more likely to
have lower mortality rates. Recently, in the Netherlands

Table 5 Multivariate analysis of survival.

Variable Odds ratio 95% CI p
Stage
2b 0.435 0.271e0.699 0.0001
3 0.831 0.531e1.300
4a 1
Figure 2 KaplaneMeier analysis of overall survival by stage.
Complications and survival for esophagectomy
locally advanced esophageal cancer patients who under-
went esophagectomy alone at 18 months and the relative
risks (95% CI) of death for treatments compared with
surgery were 0.87 (0.75e1.02) for neoadjuvant chemo-
radiation, 0.94 (0.82e1.08) for neoadjuvant chemotherapy,
and 1.33 (0.93e1.93) for adjuvant chemoradiation.
However, there was heterogeneity between the random-
ized controlled trials on neoadjuvant chemoradiation for
esophageal cancer. Wijnhoven et al29 found that two of the
six meta-analyses examined did not show a significant
survival benefit in patients with resectable esophageal
cancer. Moreover, besides survival outcome, toxicity should
be considered in deciding whether neoadjuvant chemo-
radiation has more benefits than surgery alone.30 The
National Comprehensive Cancer Network also recommends
neoadjuvant chemoradiation for locally advanced esopha-
geal cancer.31 We did not see the effect of adjuvant or
neoadjuvant chemoradiation on survival rates in our study;
however, this could be due to selective case bias in this
nonrandom study.
In conclusion, we have demonstrated that preoperative
BMI, dysphagia, pulmonary function test, type of surgical
technique, and operative time may help to predict the
chance of postoperative anastomotic leakage and pneu-
monia in locally advanced esophageal cancer patients,
while stage of disease may help to predict survival.
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