Title: Postoperative complications and health-related quality of life 10 years after
esophageal cancer surgery.
Authors: Joonas H Kauppila,
1,2,3
MD, PhD, Asif Johar,
1
MSc, and Pernilla Lagergren,
1
RN,
PhD.
Affiliations:
1
Surgical Care Sciences, Department of Molecular Medicine and Surgery,
Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden;
2
Cancer
and Translational Medicine Research Unit, Medical Research Center Oulu, University of
Oulu, Oulu University Hospital, Oulu, Finland; and
3
Upper Gastrointestinal Surgery,
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University
Hospital, 17176 Stockholm, Sweden.
Author correspondence and reprint requests to:
Joonas H Kauppila,
1
Surgical Care Sciences, Department of Molecular Medicine and Surgery,
Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden
Email: joonas.kauppila@ki.se,
Tel. +46 8-517 709 83, Fax: +46 8-517 762 80
Sources of support: This study was supported by the Swedish Research Council, Swedish
Cancer Society, the Cancer Research Foundations of Radiumhemmet, Sigrid Jusélius
Foundation, and Orion Research Foundation. The study sponsors had no role in the design
and conduct of the study; collection, management, analysis, and interpretation of the data;
preparation, review, or approval of the manuscript; or decision to submit the manuscript for
publication.
Running head: Postoperative complications and HRQOL
Mini-Abstract
Complications were analyzed in relation to 10-year HRQOL in a prospective nationwide
population-based Swedish cohort of 616 patients undergoing open esophageal cancer surgery,
HRQOL was impaired after complications on twelve of the 25 scales and items measured at
10-year follow-up, including physical function, fatigue, pain, dyspnea, insomnia and eating
problems.
3
Abstract
Objective: To evaluate the impact of postoperative complications on health-related quality of
life (HRQOL) up to 10 years after surgery for esophageal cancer.
Summary Background Data: The impact of postoperative complications on HRQOL past 5
years is unknown.
Methods: Some 616 patients undergoing open esophageal cancer surgery between April 2,
2001 and December 31, 2005 in Sweden were enrolled in this population-based, nationwide
and prospective cohort study. Exposure was the occurrence of predefined postoperative
complications, and the outcome was HRQOL evaluated by validated EORTC questionnaires
at 6 months, 3, 5 and 10 years after surgery. Linear mixed models, adjusted for longitudinal
HRQOL in the general population and confounders, provided mean score differences (MD)
with 95% confidence intervals (CI) for each HRQOL item and scale in patients with or
without postoperative complications.
Results: At 10 years, 104 (17%) patients were alive and 92 (88%) answered the HRQOL
questionnaires. Of these, 37 (40%) had at least one predefined postoperative complication.
Twelve of the 25 scales and items were significantly worse in patients with postoperative
complications 10 years after surgery, e.g., physical function (MD -15, 95% CI -24 to -7),
fatigue (MD 16, 95% CI 5 to 26), pain (MD 18, 95% CI 7 to 30), dyspnea (MD 15, 95% CI 2
to 27), insomnia (MD 20, 95% CI 8 to 32) and eating problems (MD 14, 95% CI 3 to 24)
compared to patients without complications.
Conclusions: Postoperative complications are associated with considerably impaired HRQOL
up to 10 years after esophageal cancer surgery.
Keywords: Esophagus; neoplasm; complications; quality of life; survivorship.
4
Introduction
Esophageal cancer, the 6
th
most common cause of cancer death globally, is characterized by
increasing incidence, demanding treatment and poor prognosis.
1, 2
The 5-year survival is
around 30-55% in patients eligible for curative treatment, and the risk of surgery-related
complications is over 40%.
3-5
The life of the patient after esophageal cancer surgery is
generally characterized by poor health-related quality of life (HRQOL).
6-8
Major
complications during treatment are known to cause deterioration of HRQOL in the short- but
also in the long term.
9-12
Moreover, complications and poor postoperative HRQOL are known
risk factors for poor prognosis.
13, 14
The impact of complications on 10-year HRQOL is thus
far not known.
We hypothesized that complications relate to poor recovery of HRQOL over time and poor
HRQOL also at 10 years after esophageal cancer surgery. The main aim of the study was to
examine the impact of complications on HRQOL at 10 years after surgery. The secondary aim
was to elucidate the HRQOL trajectory in relation to complications from 6 months to 10 years
postoperatively.
5
Methods
Study design
A nationwide Swedish, population-based, and prospective cohort study was conducted,
entitled the Swedish Esophageal and Cardia Cancer study (SECC).
8
SECC includes 616
patients, representing 90% of all patients operated with curative intent for oesophageal or
gastroesophageal junctional (GEJ) cancer in Sweden between April 2, 2001 and December
31, 2005. All patients in the cohort underwent open surgery, with majority operated by
transthoracic Ivor-Lewis esophagectomy. No minimally invasive surgeries were done during
the study period. Details about all study variables were prospectively assessed and reviewed
by the researchers according to a predefined study protocol to ensure uniformity, including
patient characteristics (age, sex), tumour characteristics (stage, histology), surgical treatment
and predefined complications occurring within 30 days of surgery. SECC is linked to the
Patient Registry and the Cancer Registry for information on co-morbidities. Moreover,
survival data was obtained from the 100% complete Swedish Registry of the Total
Population. The study was approved by the Regional Ethical Review Board in Stockholm,
Sweden. All participating patients gave informed consent.
Exposure
The main exposure of the study was complications occurring within 30 days of surgery
(yes/no). The complications were predefined by a group of experienced esophageal cancer
surgeons and researchers, and included: 1) major postoperative bleeding (exceeding 2000 ml
or requiring reoperation), 2) splenectomy (after failure of other methods of hemostasis), 3)
anastomotic insufficiency (clinically and radiologically verified), 4) necrosis of the substitute
(clinically significant ischemia with perforation or ulceration), 5) severe lymph leakage
(requiring drainage for more than 7 days or reoperation), 6) gastric perforation
