Title page:
Refractory bronchorrhea and mucinous pleural effusion caused by lung
metastasis of pancreatic cancer.
Taro Yonedaa), Hayato Koba a),
Tsukasa Ueda a) , Chihoka Nakai a)Hiroko Morita a) , Kazumasa Kaseb),
Kenta Yamamurab) , Kazuo Kasahara b).
Respiratory Medicine, Komatsu Municipal Hospital, Japan
Respiratory Medicine, Kanazawa University Hospital, Ishikawa, Japan
Corresponding author’s name: Taro Yoneda,
Respiratory Medicine, Komatsu Munucipal Hospital, Ishikawa,
Ho-60 Mukaimotoorimachi,Komatsu,Ishikawa 923-8560,Japan.
(E-mail:taroyoneda@yahoo.co.jp, Telephone Number
:0761-22-7111,Fax Number:0761-21-7155)
Key Clinical Message:
Our case indicates that when bronchorrhea and mucinous pleural effusion
with pancreatic cancer are observed,bronchorrhea due to malignant
disease should be taken into consideration and,bronchorrhea derived from
not bronchial asthma but lung metastasis of pancreatic cancer could lead
to be refractory.
Key words: Bronchorrhea,Mucinous pleural effusion, Pancreatic tumor.
(2)Text:
Introduction:
Bronchorrhea is a clinical condition in which more than 100 ml of sputum
is discharged in one day[1].Massive amount of sputum leads to
severe cough and continuous difficulty in expectoration, and daily life
gets remarkably affected. Bronchial asthma, bronchioloalveolar
adenocarcinoma, and chronic bronchitis are several causes of
bronchorrhea. Reports of bronchorrhea caused by pulmonary metastases of
pancreatic cancer are rare. Our case was also accompanied by mucinous
pleural effusion. Here, we describe a
therapeutic
course of
pulmonary metastases of pancreatic cancer with bronchorrhea and mucinous
pleural effusion.
Case Report:
Case: A 76-year-old man presented at our hospital in 2016 with a
complaint of left back pain and sputum. Chest X ray showed pleural
effusion on left lung and
mediastinal displacement(Figure
1A).
Enhanced chest-abdominal computed tomography revealed a solid tumor and
partial atelectasis, pleural effusion in the left lung, and a
multiloculated cystic mass on the head of the pancreas(Figure 1B,1C).
Fluorodeoxyglucose (FDG) accumulation was observed in the same location
during PET-CT (Figure 1D, 1E). The sputum was faint white and viscous.
The total volume of sputum in 24 hours was over 300 ml (Figure 2A). He
was therefore diagnosed with bronchorrhea. According to a blood test,
his white blood cell (WBC) count was relatively elevated. Hb, Plt,
liver
enzyme, and AMY
levels were normal.CA-19-9,sIL2receptor, and HbA1c levels were
elevated(Table 1).
Although
thoracentesis
of the left lung was attempted, pleural effusion was not aspirated
because of excessive viscous.
The patient experienced dyspnea and had a large amount of left pleural
effusion.Chest drainage was performed. Biochemical assessment of
pleural effusion could not be performed because of excessive viscous.
The
cytodiagnosis of pleural effusion showed adenocarcinoma, and pancreatic
cancer and lung cancer were suspected. For the purpose of diagnosis,
transbronchial lung biopsy was performed on
the lower left lobe of the lung.Amount of viscous sputum was confirmed
inbronchial lumen
(Figure 2B,2C).
Hematoxylin–eosin staining
revealed adenocarcinoma, which showed progression from
papillary and
mucosal fluid
production. On
immunostaining,
cytokeratin 7, MUC5AC, MUC6, CA19-9, and mesothelin were positive, while
napsin A and TTF-1 were negative (Fig3). Epidermal growth factor
receptor mutations and the ALK fusion gene were also negative. Bacterial
culture of the bronchoalveolar lavage was negative. Therefore, the
diagnosis was believed to be metastasis of invasive pancreatic cancer
after a course of therapy upon admission. Although chest drainage was
performed,over 1000 ml of pleural effusion was drained each day.
Although pleurodesis was performed twice, the pleural effusion did not
decrease. A trend toward dehydration appeared and was accompanied by
drainage. In addition, as a systemic chemotherapy, gemcitabine
monotherapy was administered, but the pleural effusion did not decrease.
Afterward, the patient experienced bacteremia, and his dyspnea worsened.
This patient exhibited a poor performance status and he died of his
illness. The bronchorrhea did not improve during the entire course of
his illness.
Discussion:
Bronchorrhea is a condition in which a large amount of sputum is
discharged (over 100 ml per day). Simply, this term is used to describe
airway hypersecretion with a large volume of
sputum[1]. Bronchorrhea is thought to be derived
from malignant disease in 5%–20% of the
cases[2].In non-small cell lung carcinoma, the
frequency of bronchorrhea is less than 1%. It is well known that
bronchorrhea is a characteristic of alveolar epithelial cancer and
therefore the frequency of bronchorrhea is 6%–24% in these
cancers[1]. In terms of lung cancer and metastatic
lung cancer, bronchorrhea has only been reported in the adenocarcinoma
type. Furthermore, it was reported that cultured cells derived from lung
tumors exhibited exocrine function.
As a result, secretion hyperactivity of epithelial cell-derived tumor
cells is thought to be a cause of bronchorrhea[3].
Bronchorrhea with colon cancer, cervical cancer, and pancreatic cancer,
such as in our case, has also been reported [4]
[5] [6]. Our case had symptoms characteristic of mucinous
pleural effusion. Because mucinous pleural effusion with
intrathoracic progression of pseudomyxoma peritonei is relatively
common, lung adenocarcinoma is rarely associated with mucinous pleural
effusion. In this case, it is believed that direct invasion of the
pleura by the lung cancer led to the mucinous pleural effusion. In our
case, the mucinous pleural effusion was thought to be derived from lung
metastasis of pancreatic cancer. With regard to the treatment of the
tumor-induced bronchorrhea, the decrease in bronchorrhea after
inhalation of indomethacin in alveolar epithelial cancer has been
reported[7].Moreover, it has been reported that
epidermal growth factor controls mucin secretion in airway epithelium in
alveolar epithelial cancer. Presumably, epidermal growth factor receptor
directly suppresses the secretory function of
tumors[8].In the lung cancer experiment, it was
demonstrated that gefitinib exhibited anti-tumor effects and that it
directly suppressed exocrine function. In our case, because of the
difficulty in internal use and lower performance status, this patient
had no choice except anticancer drug infusion. Unfortunately, the
anticancer treatment was refractory to bronchorrhea and mucinous pleural
effusion.Characteristically, the dehydration trend appeared to be
accompanied by drainage.In conclusion, we experienced a case of
bronchorrhea and mucinous pleural effusion derived from lung metastasis
of pancreatic cancer. The anticancer treatment was refractory to
bronchorrhea and the mucinous pleural effusion.
ACKNOWLEDGMENTS
We sincerely thank all persons who related to the diagnosis, treatment,
and nursing for the patients. Published with written consent of the
patient.
The authors declare that they have no conflicts of interest (COI).
(3)References
[1] S. Shimura, T. Sasaki, H .Sasaki, et al.
Chemical
Properties of Bronchorrhea Sputum in Bronchial
Asthma.Chest.1989;94:6:1124–1125.
[2] S. Rubiales. A, D. L. Cruz, Bezero.JA, et al. Erlotinib or
gefitinib as first-choice therapy for bronchorrhea in bronchioloalveolar
carcinoma. J Pain
Symptom Manage.2014;47:6:e7–e9.
[3] T. Kitazaki, H. Soda ,S .Doi, et.al. Gefitinib inhibits MUC5AC
synthesis in mucin-secreting non-small cell lung cancer cells. Lung
Cancer.2005;50:1:19–24.
[4] S.Shimura, T.Takashima. Bronchorrhea from Diffuse Lymphangitic
Metastasis of Colon Carcinoma to the Lung.Chest.1994;105:1:308–310.
[5] O.Epaulard, D.Moro,T.Langin. Bronchorrhea revealing cervix
adenocarcinoma metastastic to the lung.
Lung Cancer. 2001;
31:2–3:331–334.
[6] T.Lembo, T.Donnely. A Case of Pancreatic Carcinoma Causing
Massive Bronchial Fluid Production and Electrolyte
Abnormalities.Chest.1995;108:4:1161–1163.
[7] S.Homma,M.Kawabata,K.Kishi,et al. Successful treatment of
refractory bronchorrhea by inhaled indomethacin in two patients with
bronchioloalveolar carcinoma.
Chest. 1999;115:5:1465–1468.
[8] K.Takeyama,K.Dabbagh,HM.Lee,et al. Epidermal growth factor
system regulates mucin production in airways.
Proc Natl Acad Sci U
S A. 1999;Mar 16;96:6:3081–3086.
Figure legends:
Figure 1.A chest X-ray showed pleural effusion in the left lung (A).
Enhanced chest-abdominal computed tomography showed the presence of a
solid tumor and partial atelectasis as well as pleural effusion in the
left lung (B, C). FDG accumulation was observed in the same location
during PET-CT (D, E).
Table 1. Laboratory findings on admission.
Figure 2.The total volume of sputum over 24 hours was over 300 ml (A).
The properties of the sputum were endobronchially observed during
bronchoscopic examination (B, C).
Figure 3.On immunostaining, cytokeratin 7, MUC5AC, MUC6, CA19-9, and
mesothelin were positive, whereas napsin A and TTF-1 were negative.