―Original―
Analysis of Risk Factors for Postpneumonectomy Bronchopleural Fistulas in Patients with Lung Cancer Shuji Haraguchi1,2, Kiyoshi Koizumi2, Masafumi Hioki1, Tomomi Hirata2, Kyoji Hirai2, Iwao Mikami2, Hirotoshi Kubokura2, Yutaka Enomoto2, Hiroyasu Kinoshita1,2 and Kazuo Shimizu2 1
Department of Surgery, Nippon Medical School Musashi Kosugi Hospital
2
Division of Respiratory Surgery, Department of Surgery, Nippon Medical School
Abstract Background: Bronchopleural fistula is a poentioally fatal complication of pulmonary resections, especially pneumonectomy. Methods: Univariate and multivariate analyses of the development of bronchopleural fistula were performed in 12 patients with bronchopleural fistula and 102 patients without bronchopleural fistula who had undergone pneumonectomy from January 1983 through December 2005. Results: Bronchopleural fistula developed after pneumonecotomy in 12 patients (8.5%). Seven (58.7%) of the 12 patients died of bronchopleural fistula. Univariate analysis showed that preoperative infection, right pneumonectomy, and pathological N2, 3 disease significantly contributed to the development of postpneumonectomy bronchopleural fistula (p=0.0002, p= 0.0043, and p=0.0387, respectively). Multivariate analysis also showed that preoperative infection, right pneumonectomy, and pathological N2, 3 disease were significant risk factors for postpneumonectomy bronchopleural fistula. Conclusions: Bronchopleural fistula is strongly associated with preoperative infection, right pneumonectomy, and pathological N2, 3 disease. Bronchial stump coverage with pedicled tissue flaps and preservation of the bronchial arteries during mediastinal lymphnode dissection are recommended to maintain the blood supply to the bronchial stump in patients at risk. (J Nippon Med Sch 2006; 73: 314―319) Key words: lung cancer, bronchopleural fistula, pneumonecotmy
postpneumonectomy BPF is important to properly Introduction
manage patients at risk and to prevent development of postpneumonectomy BPF. In 1996, we analyzed
Postpneumonectomy bronchopleural fistula (BPF) is a potentially fatal complication of respiratory surgery
1 ― 9
.
Analysis
of
risk
factors
for
76 patients with lung cancer and found that right pneumonectomy,
preoperative
infection,
and
metastasis to a subcarinal lymph node were risk
Correspondence to Shuji Haraguchi, MD, Department of Surgery, Nippon Medical School Musashi Kosugi Hospital, 1―396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211―8533, Japan E-mail:
[email protected] Journal Website (http:! ! www.nms.ac.jp! jnms! ) 314
J Nippon Med Sch 2006; 73 (6)
Postpneumonectomy Bronchopleural Fistulas
Ta bl e1 Cl i ni c a lc ha r a c t e r i s t i c so ft he1 2pa t i e nt swi t hbr o nc ho pl e ur a lf i s t ul a s Pa t i e nt Age /Si deo ft he Ppo FEV1 . 0 Pa c kPa t ho l o gi c a l Tr e a t me nt Sur vi va l Pa t ho l o gy St a ge I nf e c t i o n Ons e t No . Se x t ho r a x ( L) ye a r s TN ( da y) ( da y) 1 .
6 9 M
Ri ght
0 . 6 6
7 0
Sq
pT3 N2
I I I
―
9
2 . 3 .
7 4 N 5 2 M
Le f t Ri ght
1 . 3 9 1 . 3 3
1 0 0 4 5
Sq Sq
pT4 N2 pT2 N2
I I I I I I
― ―
7 1 6
4 .
6 2 M
Le f t
0 . 9 4
1 4 1
Sq
pT2 N2
I I I
AP
1 2
5 .
4 7 M
Ri ght
1 . 4 6
4 0
Sq
pT3 N2
I I I
POP
1 0
6 .
5 7 M
Ri ght
1 . 1 0
3 8
Sq
pT4 N2
I I I Pyo t ho r a x 1 8
7 .
5 9 M
Ri ght
1 . 1 6
3 4
Sq
pT2 N2
I I I
―
1 0
8 . 9 . 1 0 . 1 1 . 1 2 .
5 6 M 5 9 M 7 2 M 5 3 F 3 4 M
Ri ght Ri ght Le f t Le f t Ri ght
1 . 1 3 1 . 3 7 1 . 3 4 0 . 9 5 1 . 0 5
5 0 6 3 1 0 5 0 8 0
Sq Ad Sq Ad Ot he r
pT2 N2 pN2 N0 pT4 N2 pT4 N1 pT4 N2
I I I I I I I I V I V
― ― ― Abs c e s s Abs c e s s
4 5 1 7 1 4 2 0 1 0
BSC( I CMF) +TP CTD BSC( OMF) a f t e rF BSC( OMF) a f t e rF BSC( LDF) a f t e rF BSC( PMF) a f t e rF BSC( PMF) a f t e rF CTD CTD F CTD F
8 7 D 1 0 D 7 5 D 5 8 2 D 3 0 5 D 3 7 D 9 6 D 3 3 4 D 3 7 8 A 2 4 D 1 2 2 D 1 0 D
Ppo FEV1 . 0 =pr e di c t e d po s t o pe r a t i ve f o r c e d e xpi r a t o r y vo l ume i n 1s e c o nd, Sq=s qua mo us c e l lc a r c i no ma , s pi r a t i o n pne umo ni a ,POP=po s t o bs t r uc t i ve pne umo ni a ,CTD=c he s tt ube dr a i na ge , Ad=Ade no c a r c i no ma ,AP=a c o s t a lmus c l ef l a p,TP=t ho r a c o pl a s t y,OMF=o me nt a lf l a p,LDF= l a t i s s i musdo r s if l a p, F=f e ne s t r a t i o n,I CMF=i nt e r D=de a d, A=a l i ve . PMF=pe c t o r a l i smus c l ef l a p,
factors for postpneumonectomy BPF3. Since then,
Department of Surgery, Nippon Medical School
additional risk factors have been identified: previous
Musashi Kosugi Hospital. Twenty-eight patients
ipsilateral thoracotomy4, preoperative chemotherapy
without BPF were excluded due to the lack of
4
5―7
or radiotherapy or both , right pneumonectomy , 5,7
6
detailed data. Therefore, 114 patients including 12
lower
patients with BPF and 102 patients without BPF
preoperative forced expiratory volume in 1 second
were subjected to univariate and multivariate
mechanical
ventilation ,
benign
disease ,
6
(FEV1.0) , diffusion capacity of lung to carbon monoxide6, lower preoperative serum hemoglobin6, bronchial
stump
6,7
coverage
,
completion
6
analyses. The postoperative pulmonary functions were predicted according to a simplified system, which we
6
developed using plain chest roentgenograms of
6
increased intravenous fluid in the first 12 hours ,
patients with primary lung cancer9. The predicted
blood transfusions6, predicted postpneumonectomy
postoperative FEV1.0 (ppoFEV1.0) is (42-R)! (42-T)
FEV1.07, chronic obstructive pulmonary disease7, and
preoperative FEV1.0, where R is the number of
pneumonectomy , timing of chest tube removal ,
8
length of the resection margin . Therefore, we
subsegments scheduled for lung resection and T is
reanalyzed risk factors for postpneumonectomy BPF
the number of tumor-related subsegments. T is
in a larger series, adding some risk factors reported
determined as follows: a) if a tumor is located in the
recently.
periphery of the lung, the T factor is equal to 1 in the case of a tumor 3 cm or less in its largest dimension and equal to 2 in the case of a tumor
Materials and Methods
more than 3 cm in its largest dimension; and b) if a From January 1983 through December 2005, 142
tumor obstructs large airways, the T factor is equal
patients underwent pneumonectomy for lung cancer
to the number of subsegments showing atelectasis
at the Division of Respiratory Surgery, Department
or postobstructive pneumonia9.
of
Surgery,
Nippon
Medical
J Nippon Med Sch 2006; 73 (6)
School
and
the
The lung cancers of all patients were staged 315
S. Haraguchi, et al
Ta bl e2 Cha r a c t e r i s t i c so fpa t i e nt swi t hbr o nc ho pl e ur a lf i s t ul a( BPF)a ndno nBPF
Numbe ro fpa t i e nt s Age Se x Ma l e Fe ma l e Smo ke ra ndExs mo ke r No ns mo ke r Numbe ro fc i ga r e t t epa c kye a r s Al bumi n He mo gl o bi n Di a be t e sme l l i t us Ppo FEV1 . 0 Pr e o pe r a t i vet r e a t me nt Pr e o pe r a t i vei nf e c t i o n Af f e c t e ds i deo ft het ho r a x Ri ght Le f t Ope r a t i vet i me Vo l umeo fbl o o dl o s s Me t ho do fbr o nc hi a lc l o s ur e Ha nss ut ur e Me c ha ni c a l Co mbi ne dr e s e c t i o n Pa t ho l o gi c a ls t a geo fl ungc a nc e re xc l udi ngMPLC I , I I I I I , I V Pa t ho l o gi c a lT f a c t o r T1 , 2 T3 , 4 Pa t ho l o gi c a lN f a c t o r N0 , 1 N2 , 3 Hi s t o l o gi c a lt ypeo fl ungc a nc e re xc l udi ngMPLC Squa mo usc e l lc a r c i no ma Ade no c a r c i no ma Ot he r s Re s i dua lt umo ra ts t ump
BPF
no nBPF
1 2 5 8 ±1 1 1 1( 9 2 ) 1( 8 ) 1 0( 8 3 ) 2( 1 7 ) 6 4 ±3 8 3 . 6 ±0 . 6 1 2 . 6 ±2 . 0 1( 8 ) 1 . 2 ±0 . 2 0( 0 ) 5( 4 2 )
1 0 2 6 0 ±1 1 8 1( 7 9 ) 2 1( 2 1 ) 8 1( 7 9 ) 2 1( 2 1 ) 4 5 ±3 4 3 . 8 ±0 . 5 1 2 . 5 ±1 . 8 1 0( 1 0 ) 1 . 3 ±0 . 4 1 2( 1 2 ) 7( 7 )
8( 6 7 ) 4( 3 3 ) 3 2 5 ±7 6 1 , 1 0 4 ±9 6 7
2 7( 2 6 ) 7 5( 7 4 ) 3 4 6 ±1 2 4 1 , 0 0 5 ±9 9 2
Pva l ue 0 . 5 8 8 3 0 . 3 0 8 9 0 . 7 4 8 8 0 . 0 7 1 7 0 . 1 1 0 5 0 . 8 5 8 5 0 . 8 7 0 4 0 . 2 9 7 7 0 . 1 8 8 9 0 . 0 0 0 2＊
0 . 0 0 4 3＊ 0 . 5 7 1 8 0 . 7 4 5 2
8( 6 7 ) 4( 3 3 ) 5( 4 2 )
6 4( 6 3 ) 3 8( 3 7 ) 4 1( 4 0 )
0 . 7 8 9 9 0 . 9 2 1 8
1( 8 ) 1 1( 9 2 )
2 8( 2 7 ) 7 4( 7 5 )
0 . 1 5 0 3
5( 4 2 ) 7( 5 8 )
4 6( 4 5 ) 5 6( 5 5 )
0 . 8 2 1 1
2( 1 7 ) 1 0( 8 3 )
4 9( 4 8 ) 5 3( 5 2 )
0 . 0 3 8 7＊
9( 7 5 ) 2( 1 7 ) 1( 8 ) 1( 8 )
5 8( 5 7 ) 3 0( 2 9 ) 1 4( 1 4 ) 4( 4 )
0 . 4 8 2 0 0 . 4 8 0 2
Ppo FEV1 . 0 =pr e di c t e dpo s t o pe r a t i vef o r c e de xpi r a t o r yvo l umei n1s e c o nd,aDa t aa r es ho wna s ＊ a t i s t i c a ls i gni f i c a nc e me a n±s t a nda r dde vi a t i o n; pe r c e nt a gegi ve ni npa r e nt he s e s , St
pathologically according to the International Union 10
included in the statistical analyses. Preoperative
Against Cancer system . Stapling devices we used
infection included aspiration pneumonia, pyothorax,
were the Proximate Linear Stapler TLH30 (Ethicon,
postobstructive pneumonia, and lung abscess.
Cincinnati, OH, USA) and the Roticulator (U.S.
Statistical analyses were performed using the
Surgical Corp, Norwalk, CT, USA). Twenty-nine
StatView 5.0J software package (SAS Institute, Inc,
patients underwent bronchial stump coverage with
Cary, NC, USA). Univariate analyses between the
an intercostal muscle flap (18 patients), pericardial
groups were performed by means of an unpaired
flap (7 patients), or a thymus flap (3 patients). Usage
two-tailed t-tests or the chi-square test using age,
and choice of pedicled tissue flaps were left to the
sex,
surgeon s discretion in some cases even after 1996.
hemoglobin
Therefore, bronchial
ppo%FEV1.0, smoking history (smoker and ex-
316
stump
coverage
was
not
serum
albumin
concentration
concentration
before
and
serum
operation,
J Nippon Med Sch 2006; 73 (6)
Postpneumonectomy Bronchopleural Fistulas
Ta bl e3 Re s ul t so fmul t i va r i a t ea na l ys i sr e l a t e dt o de ve l o pme nt o f br o nc ho pl e ur a lf i s t ul a
Pr e o pe r a t i vei nf e c t i o n Ri ghtpne umo ne c t o my Pa t ho l o gi c a lN2 , 3
Oddsr a t i o
9 5 %c o nf i de nc e i nt e r va l
Pva l ue
2 2 . 8 3 9 0 . 1 6 8 7 . 3 4 2
3 . 3 5 4～ 1 5 5 . 4 9 5 0 . 0 3 7～ 0 . 7 5 1 1 . 0 7 4～ 5 0 . 1 7 6
0 . 0 0 1 4 0 . 0 1 9 5 0 . 0 4 2 0
smoker versus non-smoker), the number of cigarette
the
pack-years, preoperative
lung,
carcinomatosa and pyothorax (Patient 6). A 53-year-
diabetes mellitus, preoperative adjuvant treatment,
old woman with adenocarcinoma in the left upper
affected side of the thorax, duration of surgery,
lobe had a lung abscess preoperatively (Patient 11),
volume of blood loss, bronchial closure technique
and a 34-year-old man with large cell carcinoma in
(hand
the right upper lobe had lung abscess preoperatively
suturing,
infection
mechanical
of
stapling),
the
combined
resection, residual carcinoma at bronchial stump,
right
basilar
bronchus
had
pleuritis
(Patient 12).
pathological stage (stage I or II versus stage III or
Characteristics of patients with and without BPF
IV), pathological t factor (T1, 2 versus T3, 4),
who underwent pneumonectomy are shown in
pathological n factor (N0, 1 versus N2, 3), and
Table
histological type of lung cancer (squamous cell
preoperative infection, right pneumonectomy, and
carcinoma, adenocarcinoma, and others). Multivariate
pathological N2, 3 disease significantly contributed to
logistic
the development of postpneumonectomy BPF (p=
regression
tests
were
performed
with
2.
Univariate
p=0.0043,
analyses
and
p=0.0387,
showed
that
significant risk factors identified with univariate
0.0002,
respectively).
analyses. A P
