Download Stents as sole therapy for oesophageal cancer

Articles
Stents as sole therapy for oesophageal cancer: a prospective
analysis of outcomes after placement
Russell E White, Robert K Parker, John W Fitzwater, Zachariah Kasepoi, Mark Topazian
Summary
Lancet Oncol 2009; 10: 240–46
Published Online
February 17, 2009
DOI:10.1016/S14702045(09)70004-X
See Reflection and Reaction
page 203
Tenwek Hospital, Bomet,
Kenya (R E White MD,
R K Parker BS, J W Fitzwater MD,
Z Kasepoi MBchB); Department
of Surgery, Brown Medical
School, Rhode Island Hospital,
Providence, RI, USA (R E White);
Indiana University School of
Medicine, Indianapolis, IN, USA
(R K Parker); Texas Tech
University Health Sciences
Center, Lubbock, TX, USA
(J W Fitzwater); and Miles and
Shirley Fiterman Center for
Digestive Diseases,
Department of Internal
Medicine, Mayo Clinic,
Rochester, MN, USA
(M Topazian MD)
Correspondence to:
Dr Russell E White, Tenwek
Hospital, PO Box 39, Bomet,
Kenya
[email protected]
Background Therapies for inoperable oesophageal cancer include chemoradiotherapy and placement of a self-expanding
metal stent (SEMS). Few data are available regarding SEMS as sole therapy for patients with inoperable disease who
have not already received, or are unfit for, chemoradiotherapy. The aim of this study was to determine survival,
adequacy of palliation, and complications after SEMS placement as sole therapy for inoperable oesophageal cancer in
a resource-limited setting.
Methods Data were prospectively gathered on all patients with oesophageal cancer treated with SEMS between Jan 1,
1999, and May 20, 2008, at a hospital in Kenya where chemoradiotherapy is unavailable. Dysphagia scores, morbidity,
mortality, and survival were assessed. Follow-up was done during clinic visits, home visits, and by mobile phone.
Findings 1000 stents were placed in 951 patients. Long-term follow-up was obtained for 334 patients (35%) with a
median survival of 250 days (IQR 130–431, 95%CI 217–301). Mean dysphagia scores improved from 3·3 (SD 0·6)
pre-SEMS (n=697) to 1·0 (SD 1·3) for patients (n=78) still alive and 1·8 (SD 1·2) at time of death (n=165). Survival of
17 patients with follow-up who had perforation during tumour dilation (treated with SEMS) was 283 days (IQR 227–
538) similar to the 317 patients with follow-up data who did not have a perforation (245 days, 124–430). 20 patients
with a tracheo-oesophageal fistula lived a median of 142 days (IQR 73–329). Early complications occurred in 6% (54 of
951 patients) and late complications occurred in 19% (62 of 334 patients). SEMS-related mortality was 0·3% (three
of 951).
Interpretation SEMS effectively palliate inoperable oesophageal cancer. Survival may be longer than previously
reported when SEMS are placed in all patients with inoperable oesophageal cancer, as in our study, rather than those
failing or unfit for chemoradiotherapy. SEMS seem to be an appropriate technology for palliation of oesophageal
cancer in resource-limited settings. Given the proportion of patients lost to follow up, these findings merit further
confirmation.
Funding Boston Scientific Corporation (Natick, MA, USA) and Advanced Technology and Materials Company (Beijing,
China).
Introduction
Oesophageal carcinoma, the sixth most common cause
of cancer mortality, has a worldwide 5-year prognosis of
less than 10%.1,2 Dysphagia is the most common
presenting symptom. Due to the elastic properties of
the oesophageal wall, and the lack of a serosal layer
in the oesophagus, dysphagia develops late in the course
of the disease, and locally advanced cancer is usually
present by the time symptoms develop. Squamous-cell
oesophageal carcinoma has a marked geographical
variation in incidence, and is the most common cancer
in Kenya.3 At our referral hospital in western Kenya,
oesophageal carcinoma accounts for 35% of all tumours,
and 90% of patients present with inoperable disease.4
Combination chemotherapy and radiotherapy has
efficacy in the treatment of locally advanced oesophageal
cancer,5 but our patients do not have routine access to
these treatment modalities. Palliation is therefore the
treatment goal in these patients and ideally should be
minimally invasive and affordable by use of the locally
available technology, with as little need as possible for
re-intervention.6
240
Self-expanding metal stents (SEMS) are an established
palliative therapy for cancer of the oesophagus. SEMS
provide fast, complete, and life-long management of dysphagia in most patients.7,8 Outpatient placement of SEMS
is the palliative treatment of choice at our institution,
located in a resource-limited area of rural western Kenya.9
This study was designed to assess the outcomes of
inoperable patients with symptomatic oesophageal cancer
who were treated solely with SEMS placement.
Methods
Patients
All patients were cared for at a single institution, Tenwek
Hospital in Bomet, Kenya, between Jan 1, 1999, and May 20,
2008. Patient data were obtained from a prospectively
collected, standardised database. Patients with dysphagia
due to inoperable oesophageal cancer (panel) were offered
treatment with SEMS. Informed consent was obtained
from all patients and their available family members before
undergoing endoscopy, dilation, or stent placement. This
study was approved by the ethical review committee at
Tenwek Hospital. A few patients included in the database
www.thelancet.com/oncology Vol 10 March 2009
Articles
who were enrolled on this study were also described in
initial reports of SEMS placement without fluoroscopy9
and SEMS placement for iatrogenic perforation.10
Additionally, a few patients are participants in an ongoing
prospective trial comparing SEMS diameters.
Procedure
Before stent placement, patients clinically suspected to
have oesophageal cancer because of progressive
dysphagia were referred for endoscopy. Most patients
declined sedation for endoscopy, because it doubles the
cost of the procedure (from around US$13 to $26). All
patients received pharyngeal topical anaesthesia. Before
endoscopy, the possibility of SEMS placement was
discussed with patients, especially those who did not
appear to be candidates for surgery (panel); about half
were potential candidates for surgery or decided not to
undergo SEMS placement, usually because of cost (the
average cost of an Advanced Technology and Materials
[Beijing, China] SEMS was about $200 during the study
period). Endoscopic visualisation of the tumour was
done and biopsies were typically taken for confirmation. If the tumour prevented passage of a 9·8-mm
diameter endoscope, it was progressively dilated with
tapered dilators (Savary-Gillard; Wilson Cook Medical,
Winston-Salem, NC, USA) after the passage of a guidewire as previously described.9 Patients choosing not to
receive SEMS also underwent dilation to provide some
relief of dysphagia. Tumour dilation was necessary in
about 90% of patients in this series. After dilation, the
endoscope was passed through the tumour to the
stomach, proximal and distal tumour margins were
visualised, and the distance of these tumour margins
from the incisors was noted. A SEMS was then deployed
under direct endoscopic visualisation without the use of
fluoroscopy, as previously described.9 All patients with a
stent crossing the gastro-oesophageal junction were
informed of the likelihood of reflux and prescribed acidblocking medication. Patients with a tracheo-oesophageal
fistula were given indefinite, suppressive antibiotics in
an attempt to reduce morbidity from pneumonia.
Diagnosis and treatment were often done during the
same initial visit and during one endoscopic procedure.
Statistical analysis
Dysphagia scores were noted prospectively, both before
and after stent placement, by use of Ogilvie’s scale: 0=able
to swallow a normal diet; 1=able to swallow some solids;
2=able to swallow semi-solids only; 3=able to swallow
only liquids; 4=unable to swallow saliva.11 Systematic,
prospective efforts were made to obtain follow-up data by
several methods: patients were interviewed at the time of
return visits to the hospital outpatient clinics; home visits
were made by endoscopy personnel for patients who lived
within Tenwek Hospital’s community health catchment area (the two surrounding districts representing
a radius of about 75 km); and patients with mobile phones
www.thelancet.com/oncology Vol 10 March 2009
were contacted by phone to obtain follow-up data.
Follow-up data were sought at 3-month intervals after
SEMS placement. For patients who died, date of death
and symptoms present at death were obtained from
family members. Outcome was assessed with regard to
early complications (including chest pain, perforation,
bleeding, infection, and death), late complications
(including stent migration, overgrowth, obstruction,
tracheo-oesophageal
fistula,
and
gastrointestinal
Panel: Indications and contraindications for SEMS
placement at Tenwek Hospital
Indications for SEMS as opposed to surgical resection
• Distant metastases
• Tracheo-oesophageal fistula
• Phrenic or recurrent laryngeal nerve palsy
Relative indications for SEMS as opposed to surgical
resection
• Age >80 years
• Extreme cachexia or malnutrition
• Poor exercise tolerance
• Marked medical comorbidities
• HIV positivity
Absolute contraindications for SEMS
• Tumour involving the upper oesophageal sphincter
Relative contraindications for SEMS
• Extensive tumour involvement of the gastric cardia
Patients
Patient demographics
Patients, n
Age (years), mean (SD)
951
62 (14)
Age ≥50 years, n
547/702
Male sex , n
443/715
Kalenjin ethnicity , n
305/683
Preprocedure dysphagia score, mean (SD)
3·3 (0·6)
Procedure and tumour specifics
Tumour length (cm), mean (SD)
Maximum dilation size (mm), median (IQR)
5·8 (2·7)
14 (13–15)
Tumour histology
Squamous-cell carcinoma, n
Adenocarcinoma, n
Other, n
Unknown or not recorded, n
339/360
18/360
3/360
591/951
Type of stent
AT&M SEMS (Advanced Technology and
Materials, Beijing, China), n
612/1000
Ultraflex (Boston Scientific Corporation,
MA, USA), n
289/1000
Wallstent (Boston Scientific Corporation,
MA, USA), n
14/1000
Other or unknown or not recorded, n
85/1000
Table 1: Characteristics of patients who underwent SEMS placement
241
Articles
Role of the funding source
1·0
The sponsors of this study had no role in the design of
the study, data collection or analysis, data interpretation,
or manuscript preparation. The sponsors did not have
access to study data. The corresponding author had full
access to all the data and the final responsibility to submit
for publication.
Proportion surviving
0·75
0·5
Results
0·25
Median survival
250 days
0
0
200
400
600
800
1000
1200
1400
Follow-up time (days)
Number at risk
334
137
37
10
5
3
2
Figure 1: Kaplan-Meier analysis of survival for all patients with follow-up (n=334)
Number of
complications
Early complications
Perforation
Bleeding
Severe chest pain
Death
34*
7
10
3
Late complications†
Overgrowth or obstruction
55
Migration
3
Tracheo-oesophageal fistula after SEMS placement
8
SEMS=self-expanding metal stent. 10 patients had both an early and late
complication. *37 perforations occurred in the 1950 patients undergoing
endoscopic dilation of an oesophageal tumour during the study period, 34 of
whom were treated with SEMS placement. Overall perforation frequency was
1·9%. †Occurring in 62 of 334 patients with long-term follow-up; four patients
had obstruction or overgrowth twice.
Table 2: Procedure-related complications
haemorrhage), dysphagia scores, and survival.
Performance scores were not prospectively collected for
most patients in this study, with data available for only
26 patients.
Results were noted as mean (SD) and as medians with
IQR when appropriate. Survival was expressed as median
survival in days to death and also assessed by the
Kaplan-Meier method by using patients still alive at the
time of last follow-up as the censored variable. p<0·05
was considered statistically significant. Variables that
were significant for survival at p<0·1 (ie, tracheooesophageal fistula at presentation, perforation, male
sex, and age under 50 years) were included in a Cox
proportional hazard analysis of risk factors. Data analysis
was done with Microsoft Excel, Epi Info version 3.4.3,
and STATA/IC 10.1.
242
1000 stents were placed in 951 patients. Patient
characteristics are shown in table 1. The median age at
presentation was 62 years (range 20–99; IQR 53–71). The
male to female ratio was 1·6:1. Mean pre-endoscopy
dysphagia score was 3·3 (SD 0·6), with 96% of patients
(667 of 697), for whom data was available, scoring three or
above. Pathology reports of oesophageal biopsy were
available on the hospital endoscopy database for nearly
half of the patients; others had previously undergone
biopsies at other institutions, did not undergo biopsy, or
their biopsy result was not recorded in the endoscopy
database. The proportion of patients with squamous-cell
oesophageal carcinoma was 94% (339 of 360). The most
common contraindication to surgery was extreme cachexia
and malnutrition. Three patients were deemed inoperable
because of HIV infection; until 2005, CD4 counts and
highly active antiretroviral therapy were not available to
our patients. Most stents were placed in patients on an
outpatient basis in our endoscopy clinic, and various types
of stent were used (table 1). Complete data on stent
diameters and lengths was not available, and these
variables could not be assessed in univariate analysis.
Covered stents were placed in 819 of 915 patients (90%).
Follow-up data were available for 334 of 951 (35%)
patients with a mean follow-up time of 207 days (SD 187;
[range 2–1277]). 74 patients with mobile phones were
successfully contacted, 17 of whom were still alive at the
time of most recent follow-up. Follow-up data were
obtained during clinic visits for 106 patients. The rest of
the follow-up data for the 154 remaining patients were
obtained during home visits.
195 patients were followed until the end of life, and
139 were alive at the time of the most recent follow-up, a
mean of 184 days after SEMS placement (SD 187;
range 6–1277). Overall, Kaplan-Meier median survival was
250 days (IQR 130–431, 95%CI 217–301) (figure 1). Of
the patients who were alive at the time of the most recent
follow-up, 70 of 78 (90%) reported continued improvement
in dysphagia, with a mean dysphagia score of 1·0 (SD 1·3).
For patients who died, mean dysphagia score at death (as
reported by family members) was 1·8 (SD 1·2), with 129 of
165 (77%) reporting improvement, 36 of 165 (20%) reporting no change, and five of 165 (3%) reporting worsened
dysphagia compared with initial presentation.
A tracheo-oesophageal fistula was present on initial
diagnosis of cancer in 41 patients. Follow-up data available
for 20 patients with a tracheo-oesophageal fistula showed a
median survival of 142 days (IQR 73–329; p=0·08 compared
www.thelancet.com/oncology Vol 10 March 2009
Articles
with the remainder of the study cohort who had a median
survival of 257 days [IQR 136–431]). Eleven of these patients
were followed until death at a median of 94 days
(IQR 50–177) after SEMS placement, and nine were still
alive at the time of most recent follow-up. Data regarding
dysphagia were available for 15 patients with a tracheooesophageal fistula; 13 showed an improvement in
symptoms after SEMS placement. Tracheo-oesophageal
fistula was diagnosed after SEMS placement in an
additional eight patients; median time to diagnosis was
177 days (IQR 150–254; range 88–396) post-procedure. Four
of these patients underwent placement of a second stent.
Only two patients who developed a tracheo-oesophageal
fistula after SEMS placement were followed until death;
one received a second stent, the other elected not to
undergo further intervention, and each lived for one month
after the diagnosis of the tracheo-oesophageal fistula.
Procedural-related complications are shown in table 2.
Although pain was adequately treated post-procedure with
codeine for most patients, ten of 951 needed additional
analgesics. No stents were removed due to intolerable pain.
During the study period, 1950 oesophageal tumour-dilation
procedures were done at Tenwek Hospital, with perforation
occurring in 37. 34 of the 37 patients were treated with
immediate SEMS placement. For some of these 34 patients,
SEMS placement had not been originally planned. One of
the 34 patients with a perforation who received SEMS and
the three patients with a perforation who underwent
surgery died within 30 days of the procedure. Long-term
follow-up data were available for 17 of the remaining
33 patients, with nine patients still alive at the time of the
most recent follow-up (mean 187 days [SD 112]) and eight
followed until death at a median of 261 days (IQR 198–453)
after SEMS placement, resulting in Kaplan-Meier median
survival of 283 days (IQR 227–528). Because only half of
all patients undergoing tumour dilation had SEMS
placement at our institution, but almost all patients with a
perforation received a SEMS as therapy for their perforation
(even if SEMS placement was not planned beforehand),
we have reported the incidence of perforation using all
1950 tumour dilation procedures as the denominator.
Three procedural-related deaths occurred within 30 days
of stent placement. One patient who had a stent placed
after an iatrogenic perforation during dilation of a bulky
tumour died within the first week of ongoing sepsis,
despite aggressive inpatient antibiotic therapy. A patient
with advanced carcinoma and vocal-cord paralysis, who
was stented without complication, presented 12 days after
the procedure with altered mental status and left empyema.
Despite appropriate treatment with a chest tube and
intravenous antibiotics, the patient never regained
consciousness and died 16 days after stent placement. The
third patient died at home during the night of the date of
discharge from the hospital. After stent placement, the
patient had been observed overnight at the hospital with
no significant chest pain, and was swallowing at discharge.
The family reported that the patient was doing well on
www.thelancet.com/oncology Vol 10 March 2009
arrival at home and died suddenly. Although the cause is
unknown, we included this patient as a procedural-related
death because of the time course.
Symptomatic tumour overgrowth of the stent was
diagnosed in 51 of 334 patients during follow-up at a
Initial
group,
n
Patients
with
follow-up
data, n
Median survival p value
p value
(days), IQR
(Wilcoxon) (Log-rank)
Age (years)
≤50
156
67
128 (86–399)
>50
547
263
263 (144–455)
Men
443
206
216 (121–376)
Women
272
127
304 (159–552)
Kalenjin
305
187
237 (116–375)
Non-Kalenjin
378
137
315 (146–430)
1 or 2
30
15
310 (216–352)
3 or 4
667
309
247 (127–431)
<4
429
205
252 (144–430)
4
268
119
233 (114–442)
<3
N/A
107
175 (91–314)
3 or 4
N/A
58
181 (115–281)
Mobile ‘phone
N/A
74
208 (134–498)
Home visit and clinic records
N/A
260
254 (118–426)
Proximal edge ≤ 8 cm of UOS
230
121
265 (136–430)
Proximal edge >8 cm from UOS
470
196
248 (123–450)
Sex
Ethnicity
Initial dysphagia score
Initial dysphagia score
Dysphagia score at death
Type of follow-up
Proximal measurement of tumour
Maximum dilation before SEMS placement
<14 mm
188
65
233 (114–406)
≥14 mm
280
138
192 (95–438)
Perforation treated with SEMS placement
Yes
34
17
283 (227–528)
No
685
317
245 (124–430)
Yes
41
20
142 (73–329)
No
678
314
257 (136–431)
339
154
250 (137–389)
18
10
331 (90–533)
TOF diagnosed at initial presentation
0·015
0·062
0·037
0·0010
0·21
0·44
0·20
0·61
0·32
0·42
0·86
0·26
0·61
0·17
0·41
0·43
0·18
0·62
0·094
0·18
0·087
0·27
0·52
0·58
0·10
0·078
0·50
0·54
Histology
Squamous-cell carcinoma
Adenocarcinoma
Tumour length
≤6 cm
314
146
281 (159–533)
>6 cm
329
160
226 (125–413)
AT&M
612
154
228 (115–430)
Ultraflex
289
153
249 (141–410)
Type of stent
IQR=interquartile range. UOS=upper oesophageal sphincter. SEMS=self-expanding metal stent. TOF=tracheo-oesophageal
fistula. AT&M=Advanced Technology and Materials Company. Table includes all patients with follow-up (n=334).
Table 3: Univariate analysis of variables potentially affecting median survival
243
Articles
Hazard ratio (95% CI)
Coefficient (SE)
p value
Z value
Age ≤ 50 years (yes/no)
1·26 (0·87–1·83)
0·23 (0·19)
1·24
0·217
Perforation (yes/no)
0·62 (0·30–1·26)
–0·49 (0·37)
–1·32
0·186
Women (yes/no)
0·63 (0·46–0·87)
–0·48 (0·16)
–2·85
0·004
TEF at time of presentation (yes/no)
1·09 (0·57–2·07)
0·08 (0·33)
0·25
0·799
TEF=tracheo-oesophageal fistula.
Table 4: Cox proportional hazard analysis for all clinical and endoscopic factors with p<0·1 in univariate
analysis
Women
Men
1·00
Proportion surviving
0·75
0·50
0·25
Median survival
Women=303 days
Men=216 days
0
0
200
400
600
800
1000
1200
3
0
2
0
1400
Follow-up (days)
Number at risk
Women
Men
127
206
63
74
22
15
7
3
5
0
Figure 2: Kaplan-Meier analysis of survival for all patients with follow-up, by sex
median of 144 days after SEMS placement (IQR 79–251).
30 patients elected to have an additional stent placed, and
four of these underwent placement of a third stent for a
second obstruction or overgrowth.
The effects of clinical and endoscopic variables on
long-term survival are shown in tables 3 and 4. In the
univariate analysis (table 3), age less than or equal to
50 years (p=0·015) and male sex (p=0·037) were both
associated with a shorter median survival. In a Cox
proportional hazards model, male sex was the only
variable predictive of shorter median survival (table 4).
Survival curves by sex are shown in figure 2.
Discussion
This cohort study provides both early and late
complications and survival data for a large, consecutive
series of patients with symptomatic, inoperable
oesophageal cancer who were treated with SEMS
placement as sole therapy. This study also includes a
large, single-centre experience with SEMS placement for
two important complications of oesophageal cancer:
tracheo-oesophageal fistula and iatrogenic perforation.
The median survival of patients with follow-up data was
250 days.
244
Although staging with CT or endoscopic ultrasonography is not available in our region, most patients
had obstructive malignancies that prevented the passage
of a 9·8-mm diameter video endoscope. Previous studies
have shown that 85% of such patients have locally
advanced T3–4 or N1 disease.12 Furthermore, in patients
deemed operable at our institution, 71% had T3–4 or
N1 disease, or both, at the time of resection. Thus, the
likelihood exists that almost all of our inoperable patients
treated with SEMS alone had stage 3 or 4 disease.
Survival of patients with oesophageal cancer is often
poor, even with the best available therapy. In developed
countries, 5-year survival is less than 30% for patients with
localised disease who undergo definitive radiotherapy and
chemotherapy5 and less than 40% for those undergoing
surgical resection with or without neoadjuvant therapy.13
Survival is substantially worse for the subset of patients
with locally advanced, T3–4 or N1 disease, for whom
median survival is 15–19 months, whether treated with
surgery, with or without neoadjuvant therapy, or
radiotherapy and ongoing chemotherapy.13,14 Patients with
metastatic disease and those unable to undergo intensive
therapy have an even worse survival. Worldwide 5-year
prognosis of oesophageal cancer is less than 10%.1,2
Although SEMS have no direct antitumour activity, they
probably extend the survival of symptomatic, inoperable
patients by improving nutritional intake and preventing
starvation, dehydration, and aspiration. Most studies of
SEMS from developed nations assess patient populations
who have failed previous treatment or are unfit for
chemotherapy and radiotherapy, and hence report shorter
median survivals for patients undergoing SEMS placement.
Median survival after SEMS placement ranges from 49 to
186 days in European and North American series,15–25 and is
often less than half the survival time we noted. A nonrandomised, case–control study compared chemotherapy
and radiotherapy with SEMS placement alone in 72 patients
with locally advanced disease.26 The investigators reported
an improved median survival (11 months vs 4 months)
and 5-year survival (15% vs 0%) in the patients receiving
radiotherapy and chemotherapy compared with those
receiving SEMS alone. Because patients and their
physicians chose between treatment modalities in the
aforementioned study, the likelihood exists that those who
were frailer and less fit received SEMS. Our data avoid this
bias and present a closer estimate of the expected survival
for inoperable patients with symptomatic oesophageal
cancer treated with SEMS alone. Unfortunately, data
collected prospectively during the study did not include
performance scores for most patients to assess this theory.
The median survival in this series of 8·4 months
compares favourably to other reported palliative
modalities for advanced disease, including photodynamic
therapy (4·8 months),27 laser therapy (4·1–4·6 months),28,29
and single-dose brachytherapy (4·9–7·9 months).15,30–32 It
is likely that these other palliative modalities would also
do better when not used as salvage therapies or for the
www.thelancet.com/oncology Vol 10 March 2009
Articles
least fit patients. Single-dose brachytherapy seems to be
better than SEMS in randomised trials, with a lower
frequency of complications and better quality of life.15,33
In one study, median survival was 145 days after SEMS
placement, and was similar after brachytherapy.15 The
group of Dutch investigators suggested that SEMS are
nevertheless a better option for patients with severe
dysphagia, short life expectancy, and with a need for
quick relief of symptoms.15 Most patients in this series
meet these criteria (mean dysphagia score of 3·3 in our
setting vs 2·8 in the Dutch study).
SEMS provided excellent and life-long palliation of
dysphagia for most patients in this series. 16% of patients
(54 of 334) developed symptomatic stent obstruction or
migration needing repeat endoscopic intervention. In
these patients, symptoms typically responded well to
placement of a second SEMS. An additional 6% of
patients (54 of 951) developed early complications.
Procedure-related mortality was 0·3% (three of 951). These
complication frequencies are within ranges previously
reported by other investigators.34–37 2% of patients (eight of
334) developed a tracheo-oesophageal fistula after SEMS
placement, typically at the proximal flange of the SEMS.
These tracheo-oesophageal fistulas were probably caused
by the indwelling SEMS, in combination with disease
progression, and were difficult to treat effectively.
This cohort study shows that SEMS placement is an
effective treatment strategy for patients with iatrogenic
perforation of their oesophageal tumours, and those
presenting initially with tracheo-oesophageal fistula.
These have traditionally been considered morbid
complications of oesophageal cancer, and have been
associated with high 30-day mortality. In this
series, patients treated for iatrogenic perforation with
immediate SEMS placement had a median survival of
283 days (9·4 months), very similar to the survival of the
entire cohort. Those presenting with a tracheo-oesophageal
fistula had a median survival of 142 days (4·7 months)
after SEMS placement. This shorter survival was not
significant, but determination of statistical significance
was limited by the small number of patients.
Although complete data were available regarding early
complications, long-term follow-up data were only
obtained in 35% of patients (334 of 951) undergoing SEMS
placement, which presents a major source of potential
bias in our study findings. The absence of long-term
follow-up data for 65% of patients could potentially result
in either increased or decreased complication frequencies
and life expectancy. We made systematic, prospective
attempts to obtain follow-up data. All patients with an
address were contacted by post, all those with phones were
contacted by a phonecall, and home visits were arranged
for patients living within the two surrounding districts
(about a 75-km radius). Mobile phones became widely
available in Kenya near the end of the study period.
Tenwek Hospital is a referral centre for oesophageal
disease, and many patients travel a long distance to obtain
www.thelancet.com/oncology Vol 10 March 2009
treatment at the hospital. Because travel costs are high
and most patients have limited resources, many patients
do not return to the hospital clinics for routine follow-up
visits, and might not be able to return even if symptoms
recur or complications develop. Tenwek Hospital is located
in a region populated largely by ethnic Kalenjins. The
finding that median survival was not statistically different
between Kalenjin versus non-Kalenjin patients, or between
those with follow-up by mobile phone versus home visits,
could suggest that patients living at greater distances from
the hospital did not have substantially different survival
compared with those living in the hospital region. More
comprehensive follow-up data are needed, and future
studies could improve the evidence base.
Risk-factor analysis showed only age and sex as
significant determinants of survival (p<0·05). Age 50 years
or less was associated with a decreased median survival.
This surprising finding could be due to different tumour
biology, aetiology, or stage, or possibly to delays in seeking
medical care for younger patients. No difference in
survival between young and old patients with oesophageal
cancer was seen in Turkey,38 Philadelphia (PA, USA),39 or
Los Angeles (CA, USA),40 although younger patients
typically had more advanced disease at the time of
presentation. Conversely, Chinese investigators showed
that younger patients with squamous-cell cancer had more
aggressive tumour histology and a poorer prognosis than
older patients.41 This finding deserves further study. When
assessing potential risk factors in multivariate analysis,
only male sex was a significant risk factor.
SEMS are an appropriate palliative technology for
resource-limited settings. In a single outpatient intervention, most patients with inoperable oesophageal cancer
receive durable palliation of their major symptom. In our
experience, survival after SEMS placement in such patients
is substantially longer than reported in studies from
resource-rich nations. SEMS placement requires flexible
gastroscopy equipment and an experienced operator, but
does not require fluoroscopy or the more extensive
medical infrastructure needed to deliver intensive
chemotherapy and radiotherapy. Two additional hospitals
within Kenya have recently implemented SEMS treatment
for inoperable oesophageal cancer. We believe this
technique, with appropriate training, can be adapted for
use in many resource-limited settings.
Contributions
REW and MT were responsible for the conception and design of the
study. REW, ZK, and MT were responsible for the stent placement
procedures. REW and ZK supervised data collection and assembly. REW,
RKP, and JWF were responsible for data analysis. All authors
contributed to data interpretation and writing of the manuscript.
Conflicts of interest
The authors declared no conflicts of interest.
Acknowledgments
We gratefully acknowledge Boston Scientific Corporation, Natick, MA,
USA, which donated the Ultraflex oesophageal stents used in this study.
We also thank Advanced Technology and Materials Company, Beijing,
China, for supplying SEMS at reduced cost.
245
Articles
References
1
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002.
CA Cancer J Clin 2005; 55: 74–108.
2
Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of worldwide
mortality from 25 cancers in 1990. Int J Cancer 1999; 83: 18–29.
3
White RE, Abnet CC, Mungatana CK, Dawsey SM. Oesophageal
cancer: a common malignancy in young people of Bomet District,
Kenya. Lancet 2002; 360: 462–63.
4
White RE, Kasepoi Z, Harewood GC, Ng T, Cioffi W, Topazian M.
Experience with 1,345 esophageal cancer patients seen at a single
mission hospital in western Kenya. Gastrointest Endosc 2006; 63: AB124.
5
Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally
advanced esophageal cancer: long-term follow-up of a prospective
randomized trial (RTOG 85-01). JAMA 1999; 281: 1623–27.
6
Kmietowicz Z. Tackle cancer in Africa now to prevent catastrophe,
say health activists. BMJ 2007; 334: 1022–23.
7
Baron T. Expandable metal stents for the treatment of cancerous
obstruction of the gastrointestinal tract. N Engl J Med 2001;
344: 1681–87.
8
Conio M, Repici A, Battaglia G, et al. A randomized prospective
comparison of self-expandable plastic stents and partially covered
self-expandable metal stents in the palliation of malignant
esophageal dysphagia. Am J Gastroenterol 2007; 102: 2667–77.
9
White RE, Mungatana C, Topazian M. Esophageal stent placement
without fluoroscopy. Gastrointest Endosc 2001; 53: 348–51.
10 White RE, Mungatana C, Topazian M. Expandable stents for
iatrogenic perforation of esophageal malignancies.
J Gastrointest Surg 2003; 7: 715–20.
11 Ogilvie AL, Dronfield MW, Ferguson R, Atkinson M. Palliative
intubation of oesophagogastric neoplasms at fiberoptic endoscopy.
Gut 1982; 12: 1060–67.
12 Pfau PR, Ginsberg GG, Lew R, Faigel DO, Smith DB, Kochman ML.
Esophageal dilation for endosonographic evaluation of malignant
esophageal strictures is safe and effective. Am J Gastroenterol 2000;
95: 2813–15.
13 Schwer AL, Ballonoff A, McCammon R, Rusthoven K, D’Agostino
RB, Schefter TE. Survival effect of neoadjuvant radiotherapy before
esophagectomy for patients with esophageal cancer: a surveillance,
epidemiology, and end-results study. Int J Radiat Oncol Biol Phys
2008; 72: 449–55A.
14 Bedenne L, Michel P, Bouche O, et al. Chemoradiation followed by
surgery compared with chemoradiation alone in squamous cancer
of the esophagus: FFCD 9102. J Clin Oncol 2007; 25: 1160–68.
15 Homs MY, Steyerberg EW, Eijkenboom WM, et al. Single-dose
brachytherapy versus metal stent placement for the palliation of
dysphagia from oesophageal cancer: multicentre randomised trial.
Lancet 2004; 364: 1497–504.
16 Vakil N, Morris AI, Marcon N, et al. A prospective, randomized,
controlled trial of covered expandable metal stents in the palliation
of malignant esophageal obstruction at the gastroesophageal
junction. Am J Gastroenterol 2001; 96: 1791–96.
17 Hills KS, Chopra KB, Pal A, Westaby D. Self-expanding metal
oesophageal endoprostheses, covered and uncovered: a review of
30 cases. Eur J Gastroenterol Hepatol 1998; 10: 371–74
18 Xinopoulos D, Dimitroulopoulos D, Tsamakidis K, et al. Palliative
treatment of advanced esophageal cancer with metal-covered
expandable stents. A cost-effectiveness and quality of life study.
J BUON 2005; 10: 523–28.
19 Johnson E, Enden T, Noreng HJ, et al. Survival and complications
after insertion of self-expandable metal stents for malignant
oesophageal stenosis. Scand J Gastroenterol 2006; 41: 252–56.
20 Riccioni ME, Shah SK, Tringali A, et al. Endoscopic palliation of
unresectable malignant oesophageal strictures with self-expanding
metal stents: comparing Ultraflex and Esophacoil stents.
Dig Liver Dis 2002; 34: 356–63.
21 Christie NA, Buenaventura PO, Fernando HC, et al. Results of
expandable metal stents for malignant esophageal obstruction in
100 patients: short-term and long-term follow-up. Ann Thorac Surg
2001; 71: 1797–801.
22 Gevers AM, Macken E, Hiele M, Rutgeerts P. A comparison of laser
therapy, plastic stents, and expandable metal stents for palliation
of malignant dysphagia in patients without a fistula.
Gastrointest Endosc 1998; 48: 383–88.
246
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
Cwikiel W, Tranberg KG, Cwikiel M, Lillo-Gil R. Malignant
dysphagia: palliation with esophageal stents—long-term results
in 100 patients. Radiology 1998; 207: 513–18.
De Palma GD, Galloro G, Sivero L, et al. Self-expanding metal
stents for palliation of inoperable carcinoma of the esophagus and
gastroesophageal junction. Am J Gastroenterol 1995; 90: 2140–42.
Winkelbauer FW, Schöfl R, Niederle B, Wildling R, Thurnher S,
Lammer J. Palliative treatment of obstructing esophageal cancer
with nitinol stents: value, safety, and long-term results.
AJR Am J Roentgenol 1996; 166: 79–84.
Wong SKH, Chiu PWY, Leung SF, et al. Concurrent
chemoradiotherapy or endoscopic stenting for advanced squamous
cell carcinoma of esophagus: a case control study. Ann Surg Oncol
2008; 15: 576–82.
Litle VR, Luketich JD, Christie NA, et al. Photodynamic therapy as
palliation for esophageal cancer: experience in 215 patients.
Ann Thorac Surg 2003; 76: 1687–93.
Dallal HJ, Smith GD, Grieve DC, Ghosh S, Penman ID, Palmer KR.
A randomized trial of thermal ablative therapy versus expandable
metal stents in the palliative treatment of patients with esophageal
carcinoma. Gastrointest Endosc 2001; 54: 549–57.
Spencer GM, Thorpe SM, Blackman GM, et al. Laser augmented
by brachytherapy versus laser alone in the palliation of
adenocarcinoma of the esophagus and cardia: a randomized study.
Gut 2002; 50: 224–27.
Harver JC, Fleischman EH, Bellotti JE, Kagan AR. Intracavitary
radiation in treatment of advanced esophageal
carcinoma: a comparison of high dose rate vs low dose rate
brachytherapy. J Surg Oncol 1993; 52: 101–04.
Sur RK, Donde B, Levin VC, Mannell A. Fractionated high dose rate
intraluminal brachytherapy in palliation of advanced esophageal
cancer. Int J Radiat Oncol Biol Phys 1998; 40: 447–53.
Sur RK, Levin VC, Donde B, Miszczyk L, Nag S. Prospective
randomized trial of HDR brachytherapy as a sole modality in
palliation of advanced esophageal carcinoma—an International
Atomic Energy Agency study. Int J Radiat Oncol Biol Phys 2002;
53: 127–33.
Bergquist H, Wenger U, Johnsson E, et al. Stent insertion or
endoluminal brachytherapy as palliation of patients with
advanced cancer of the esophagus and gastroesophageal junction.
Results of a randomized, controlled trial. Dis Esophagus 2005;
18: 131–39.
Cwikiel W, Stridbeck H, Tranberg K, et al. Malignant esophageal
strictures: treating with a self-expanding nitinol stent. Radiology
1993; 187: 661–65.
Adam A, Ellul J, Watkinson A. Palliation of inoperable esophageal
carcinoma: a prospective randomized trial of laser therapy and stent
placement. Radiology 1997; 202: 344–48.
Siersema PD, Hop WC, van Blankenstein M, et al. A comparison of
3 types of covered metal stents for the palliation of patients with
dysphagia caused by esophagogastric carcinoma: a prospective,
randomized study. Gastrointest Endosc 2001; 54: 145–53.
Mayoral W, Fleischer D, Salcedo J, Roy P, Al-Kawas F, Benjamin S.
Non-malignant obstruction is a common problem with metal stents
in the treatment of esophageal cancer. Gastrointest Endosc 2000;
51: 556–59.
Turkyilmaz A, Eroglu A, Subasi M, Karaoglanoglu N.
Clinicopathological features and prognosis of esophageal cancer in
young patients. Is there a difference in outcome? Dis Esophagus 2008;
published online November 12. DOI:10.1111/j.1442-2050.2008.00890.x.
Hashemi N, Loren D, Dimarino AJ, Cohen S. Presentation and
prognosis of esophageal adenocarcinoma in patients below age 50.
Dig Dis Sci 2008; published online November 23.
DOI:10.1007/s10620-008-0565-7.
Portale G, Peters JH, Hseih CC, et al. Esophageal adenocarcinoma
in patients < or = 50 years old: delayed diagnosis and advanced
disease at presentation. Am Surg 2004; 70: 954–58.
Lu JP, Xian MS, Hayashi K. Morphologic features in esophageal
squamous cell carcinoma of young adults in north China. Cancer
1994; 74: 573–77.
www.thelancet.com/oncology Vol 10 March 2009