Download Clinical Outcome After Pulmonary Resection for Lung Cancer

Toshiro Obuchi, MD, Wakako Hamanaka, MD, Yasuhiro Yoshida, MD,
Jun Yanagisawa, MD, Daisuke Hamatake, MD, Takeshi Shiraishi, MD, and
Akinori Iwasaki, MD
Department of Thoracic, Breast, Endocrine, and Pediatric Surgery, Fukuoka University Hospital, Fukuoka, Japan
Background. The number of operations for patients
with malignant tumors receiving long-term hemodialysis
has been increasing; however, there are only few reports
about pulmonary resection for the patients with lung
cancer.
Methods. Between 1995 and 2009, 11 hemodialysis
patients (6 men, 5 women; mean age, 66.4 years) with
non-small cell lung cancer underwent pulmonary resection at our institution. We retrospectively evaluated their
postoperative clinical outcomes and long-term results.
Results. The underlying kidney conditions included
nephrosclerosis in 3, diabetic nephropathy in 3, glomerulonephritis in 1, and polycystic kidney in 1; 3 patients
had undergone nephrectomy. The median duration of
hemodialysis preoperatively was 5.0 years. Three pa-
tients had been treated for previous carcinoma. The
histopathologic diagnoses were adenocarcinoma in 9
patients and squamous cell carcinoma in 2. Procedures
included lobectomy in 9, pneumonectomy in 1, and
wedge resection in 1. There were no in-hospital deaths.
Postoperative morbidity included 2 cases of pneumonia
and 1 of chylothorax. At the time of our investigation, 6
patients were dead; 2 of cancer and 4 of noncancer causes.
The overall 5-year survival rate of 11 patients was 28.0%.
Conclusions. Hemodialysis is not a contraindication to
lung resection, despite the high morbidity rate. Surgical
treatments, including lobectomy, remain one of effective
treatments for patients on hemodialysis with lung cancer.
(Ann Thorac Surg 2009;88:1745– 8)
© 2009 by The Society of Thoracic Surgeons
O
years (range, 0.5 to 23 years), with a mean duration of 6.7
years.
Pulmonary resections were performed through a posterolateral thoracotomy or using the video-assisted thoracic surgical (VATS) technique, which are the standard
procedures in our institution.
In all patients, hemodialysis through the shunt was
routine 3 days a week, on Tuesday, Thursday, and Saturday, using heparin sodium. All operations were performed on Wednesday so that the patients underwent
hemodialysis on the day before the operation and the day
after. No additional hemodialysis was done on the operative day. For the perioperative hemodialysis, nafamostat
mesylate was used instead of heparin sodium until the
chest drainage tube was removed and hemostasis was
confirmed. For priming the circuit of hemodialysis, 20 mg
of nafamostat mesylate was used, and 30 mg/h of nafamostat mesylate was continuously added into the circuit
during hemodialysis.
Antibiotics were routinely given intravenously, intraoperatively, and postoperatively. We administered 1
gram/d of an antibiotic such as piperacillin, cefazolin, or
cefotiam. On the operative day, the antibiotic was intravenously dripped at the start of the operation. Postoperatively, the antibiotic was given for a few days.
We investigated the 11 patients in terms of respiratory
functions, serum levels of urea nitrogen and creatinine,
underlying kidney condition, histology, status of lung
cancer and history, comorbidity, history of smoking,
wing to technologic progress made in hemodialysis,
the number of patients in a long-term hemodialysis has been increasing; therefore, it is reasonable to
assume that the number of hemodialysis patients with
lung cancer in need of pulmonary resection should
increase [1–3]. However, only few reports have detailed
the clinical outcomes after pulmonary resection for hemodialysis patients with non-small cell lung cancer
[4 – 6]. As such, we evaluated the clinical outcomes and
long-term results of these patients.
Patients and Methods
This study protocol was examined and approved by the
department Research Review Board. Before the operation, we had obtained a written consent from all patients
giving us permission to perform research using their
data, with an understanding that their privacy would be
protected. The board concluded that this study does not
violate patient privacy and approved the consent form.
Between January 1995 and January 2009, 11 patients (6
men, 5 women) with non-small cell lung cancer who were
also receiving hemodialysis underwent lung resection at
our institution. We retrospectively reviewed their data,
and their characteristics are reported in Table 1. The
median preoperative duration of hemodialysis was 5.0
Accepted for publication Aug 6, 2009.
Address correspondence to Dr Obuchi, Jonan-ku, Nanakuma, 7 chome,
45-1, Fukuoka, 814-0180, Japan; e-mail: [email protected].
© 2009 by The Society of Thoracic Surgeons
Published by Elsevier Inc
0003-4975/09/$36.00
doi:10.1016/j.athoracsur.2009.08.010
GENERAL THORACIC
Clinical Outcome After Pulmonary Resection for
Lung Cancer Patients on Hemodialysis
GENERAL THORACIC
1746
OBUCHI ET AL
OUTCOMES OF HEMODIALYSIS WITH LUNG CANCER
Table 1. Patient Characteristics
Variable
Patients, No.
Gender, No.
Male
Female
Age, mean (range), y
Follow-up, mean (range), d
Pathologic T N M stage, No.
IA
IB
IIB
IIIA
Histologic type, No.
Adenocarcinoma
Squamous cell carcinoma
Surgical procedure, No.
Lobectomy
Pneumonectomy
Wedge resection
Surgical approach, No.
Open thoracotomy
VATS
Respiratory function, mean ⫾ SD
Vital capacity, L
% Vital capacity
FEV1, L
FEV1, %
Serum values after hemodialysis
Urea nitrogen, mean ⫾ SD, mg/dL
Creatinine, mean ⫾ SD, mg/dL
Hemodialysis duration, median (range), y
Result
11
6
5
66.4 (51–89)
995.6 (106–4975)
6
3
1
1
9
2
9
1
1
7
4
2.91 ⫾ 0.70
102.5 ⫾ 22.5
2.04 ⫾ 0.36
78.7 ⫾ 11.1
29.4 ⫾ 16.4
4.00 ⫾ 2.39
5.0 (0.5–23)
FEV1 ⫽ forced expiratory volume in 1 second;
SD ⫽ standard deviation;
VATS ⫽ video-assisted thoracic surgery.
surgical procedure, operative time, volume of intraoperative blood loss, duration of postoperative thoracic drainage, duration of postoperative hospitalization, postoperative complication, patient prognosis, and cause of death.
Data for the 11 patients were statistically analyzed
using StatMate software (ATMS Inc, Tokyo, Japan). Using this software, we plotted Kaplan-Meier curves.
Results
The mean duration of follow-up was 995.6 days (range,
106 to 4975 days). The mean serum levels of urea nitrogen
and creatinine after hemodialysis were 29.4 mg/dL and
4.0 mg/dL, respectively.
The underlying kidney conditions included nephrosclerosis in 3 patients, diabetic nephropathy in 3, glomerulonephritis in 1, and polycystic kidney in 1 (Table 2). In
addition, 3 patients had undergone nephrectomy. The
histologic diagnosis was adenocarcinoma in 9 patients
and squamous cell carcinoma in 2. Although preoperative clinical stage was evaluated to be IA or IB for all
patients, the postoperative pathologic stages of cancer
Ann Thorac Surg
2009;88:1745– 8
were determined as IA in 6 patients, IB in 3, IIB in 1, and
IIIA in 1.
Treatment history revealed that 3 patients had already
been treated for previous primary carcinoma, comprising
colon carcinoma in 2 and renal carcinoma in 1. Also, 6
patients were current smokers at the time of admission.
Procedures included lobectomy in 9 patients, pneumonectomy in 1, and wedge resection for a tiny localized
adenocarcinoma, Noguchi type B, in 1. Operations were
done through posterolateral thoracotomy in 7 patients
and by VATS in 4. The operative time and the intraoperative blood loss are reported in Table 3. The mean
duration of postoperative thoracic drainage was 4.2 days,
and the mean duration of postoperative hospitalization
was 15.6 days. There were no hospital deaths. Postoperative complications included pneumonia in 2 patients
and chylothorax in 1. The morbidity rate was 27.3%.
Six patients had died at the time of the investigation.
Two died of lung cancer and the remaining 4 died of
noncancer causes such as acute myocardial infarction or
subarachnoid hemorrhage. The overall 5-year survival
rate was 28.0% (Fig 1), and the 5-year survival rate for
stage I patients was 37.5% (Fig 2).
Comment
Patients receiving hemodialysis have been reported to
have a potentially higher risk of cancer, and they undergo more operations in their lifetime than others [2– 4].
Maisonneuve and colleagues [3] reported high risks
associated with cancer of the kidney, bladder, and endocrine organs in patients undergoing hemodialysis, but no
increase in the incidence of cancer of the lung, colon or
rectum, breast, and stomach. Kantor and colleagues [5]
also reported that no increase in the number of patients
with lung cancer was found in hemodialysis patients, so
the relative risk for these patients was 0.8. However,
patients receiving hemodialysis are generally thought to
have weakened anticancer immune systems [4]. In fact, 3
patients (27.3%) in our study had a treatment history of
another primary carcinoma. It is unclear whether this
rate of double cancer (27.3%) in our limited experience
has some clinical meaning, but this rate seems relatively
high.
At our institution, the patients on hemodialysis could
safely undergo even major lung resections with our usual
procedures, under strict patient selection. It was reasonable that the mean volume of intraoperative blood loss
was about 150 grams, and the mean duration of thoracic
drainage was about 4 days. We think that perioperative
usage of nafamostat mesylate, which is an ultra-shortacting anticoagulant agent used in hemodialysis, is more
effective than heparin sodium in controlling intraoperative and postoperative bleeding, as Tsuchida and colleagues [6] also reported. The administration of hemodialysis with nafamostat mesylate instead of heparin
sodium did not negatively affect hemostasis perioperatively for the present 11 patients.
A high morbidity rate after pulmonary resection for
patients on hemodialysis has been reported [6]. We
OBUCHI ET AL
OUTCOMES OF HEMODIALYSIS WITH LUNG CANCER
1747
Table 2. Preoperative Characteristics of the 11 Hemodialysis Patients
Pt
Age
Sex
Histology
Stage
History, Comorbidity
1
2
3
4
5
6
7
8
9
10
11
51
68
74
89
71
60
58
68
55
73
63
F
F
M
M
M
M
F
M
F
M
F
Ad
Ad
Ad
Ad
SCC
Ad
Ad
SCC
Ad
Ad
Ad
IA
IB
IIIA
IA
IB
IA
IA
IIB
IA
IB
IA
...
...
...
...
Ad ⫽ adenocarcinoma;
AF ⫽ atrial fibrillation;
intervention;
SCC ⫽ squamous cell carcinoma.
DM, PCI, AF
DM
Renal cancer
Renal tuberculosis
Colon cancer, renal hematoma
Colon cancer, DM, PCI
...
DM ⫽ diabetes mellitus;
found complications in 3 of 11 patients. For 2 of those 3
patients, complications of pneumonia resulted in prolonged durations of postoperative hospital stays. The
27.3% morbidity rate in our series was high, even though
no fatal complications occurred. Thus, hemodialysis patients undergoing lung resection should be closely monitored postoperatively for symptoms of complications
such as pneumonia.
Japan is one of the countries with the longest life
expectancy at birth in the world, and because the elderly
population is increasing as whole, the number of elderly
patients with lung cancer has been increasing. Currently,
lobectomies are being performed even on extremely
elderly patients, such as octogenarians, provided that
they are in good performance status, the curability is
appropriate, and their quality of life is not negatively
affected [7].
Our study included an 89-year-old patient who underwent lobectomy through a posterolateral thoracotomy.
Although it is generally difficult to evaluate the operative
indication of someone who is as old as this patient, it is
F ⫽ female;
Underlying Renal
Condition
Smoking
Pack-years
Glomerulonephritis
Nephrosclerosis
Polycystic kidney
Nephrosclerosis
Diabetic nephropathy
Diabetic nephropathy
Postnephrectomy
Postnephrectomy
Postnephrectomy
Diabetic nephropathy
Nephrosclerosis
0
0
60
60
40
30
0
48
0
99
0
M ⫽ male;
PCI ⫽ percutaneous coronary
also difficult to choose other methods of treatment, such
as chemotherapy or best supportive care, in the case like
this patient, who had early-stage cancer and was in good
performance status. Radiotherapy is also a treatment
option, but it is not easy to choose radiotherapy when a
better curability can be expected from surgery. Although
lung wedge resection is usually a good surgical treatment
option, depending on the location of tumor, lobectomy
was the only option in this patient. Generally, lobectomy
has its advantage in the low recurrence rate after the
procedure, with simple postoperative follow-up and
without the need for continuous treatments, especially
for those with stage I lung cancer. With respect to our
89-year-old patient, the reason why we performed lobectomy was that first, he was healthy for his age and
expressed a strong desire to have lobectomy over other
options. Second, the average life span of 89-year-old
Japanese men is 4.70 years. In fact, he was discharged 12
days after lobectomy without any complications. At least
in this case, we think lobectomy was one of reasonable
options.
Table 3. Postoperative Characteristics of the 11 Hemodialysis Patients
Operation
Time
(min)
Blood
Loss
(g)
Duration of
Drainage
(days)
Post-op
LOS
(days)
Complication
Survival
(mon)
Follow-up
Cause of Death
...
Local recurrence
Distant metastasis
Heart failure
...
Unknown
(noncancer)
SAH
AMI
...
...
...
Pt
Procedure
1
2
3
4
5
6
Lobectomy
Lobectomy
VATS lobectomy
Lobectomy
Lobectomy
VATS lobectomy
220
260
350
205
270
130
105
75
215
100
315
40
5
4
3
2
4
5
10
15
15
12
10
13
...
...
...
...
...
...
165.8
12.5
16.3
24.1
18.3
35.1
Alive
Dead
Dead
Dead
Alive
Dead
Lobectomy
Pneumonectomy
VATS wedge resection
Lobectomy
VATS lobectomy
170
200
35
170
150
110
374
5
150
100
4
1
1
8
9
18
27
3
36
13
...
Pneumonia
...
Pneumonia
Chylothorax
5.2
27.6
39.4
17.1
3.5
Dead
Dead
Alive
Alive
Alive
7
8
9
10
11
AMI ⫽ acute myocardial infarction;
LOS ⫽ length of stay;
SAH ⫽ subarachnoid hemorrhage;
VATS ⫽ video-assisted thoracic surgery.
GENERAL THORACIC
Ann Thorac Surg
2009;88:1745– 8
GENERAL THORACIC
1748
OBUCHI ET AL
OUTCOMES OF HEMODIALYSIS WITH LUNG CANCER
In our limited study, the 5-year survival rate was 28.0%
for the 11 hemodialysis patients with lung cancer undergoing pulmonary resection and 37.5% for the 9 patients
with stage I lung cancer. Although it is problematic to
make a simple comparison between our results and the
results of patients not receiving hemodialysis [8], it is still
necessary to find a clinical meaning from our results. One
possible explanation is that arteriosclerosis, which is
largely a cardiovascular disease, has a great effect on
morbidity and mortality for hemodialysis patients [9].
Ohtake and colleagues [9] reported that cardiac death
accounts for almost 40% of total deaths among hemodialysis patients, and coronary angiography showed significant coronary artery stenosis in 53.3% of 30 asymptomatic chronic kidney disease patients at the start of
hemodialysis.
Among the many complications induced by long-term
hemodialysis are infections, chronic heart failure, and
arteriosclerosis of cerebral and cardiac arteries. In fact, 4
of the 6 deaths in our study were of noncancer causes,
including arteriosclerosis. The prognosis for those patients after lung resection might have been influenced by
their underlying complications. Nevertheless, surgical
treatments are still effective for treating lung cancer.
In conclusion, our study revealed that hemodialysis is
not a contraindication to lung resection, despite high
morbidity rate; surgical intervention is still an effective
treatment for patients on hemodialysis with lung cancer.
In our limited study, however, we were unable to refer to
differences in effectiveness between surgical intervention
and radiotherapy [10] or between lobectomy and limited
lung resection [11]. We think that further studies are
needed to establish the therapeutic tactics for hemodialysis patients with lung cancer, especially early-stage
cancer.
Fig 1. Kaplan-Meier curves show overall survival after pulmonary
resection for hemodialysis patients with non-small cell lung cancer.
The 5-year survival rate was 28.0%.
Ann Thorac Surg
2009;88:1745– 8
Fig 2. Long-term survival after pulmonary resection is shown for hemodialysis patients with stage I lung cancer. The 5-year survival rate
was 37.5%.
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