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□ ORIGINAL ARTICLE □

Interstitial Lung Disease after Pleurodesis
for Malignant Pleural Effusion

Norihito Yokoe 1, Eisuke Katsuda 2, Kenshi Kosaka 1, Rie Hamanaka 1, Ayako Matsubara 1,
Masaki Nishimura 1, Hiroyuki Tanaka 1, Nobuhiro Asai 1, Ayumu Takahashi 1,
Toshiki Kawamura 2, Tsuneo Ishiguchi 2, Etsuro Yamaguchi 1 and Akihito Kubo 1

Abstract

Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung
disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteris-
tics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk
factors for ILD in patients who underwent pleurodesis to control MPE.
Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between
March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively ana-
lyzed.
Results A total of 84 patients underwent pleurodesis, all using OK-432. ILD occurred in 13 patients
(15.5%). The development of ILD after pleurodesis was significantly associated with old age (odds ratio
[OR]: 4.82, 95% confidence interval [CI]: 1.22-19.08) and epidermal growth factor receptor-tyrosine kinase
inhibitor (EGFR-TKI) treatment (OR: 5.97, CI: 1.7-20.9). A multivariate analysis revealed that >67 years of
age (p=0.01) and EGFR-TKI treatment (p=0.02) were significantly associated with the development of
pleurodesis-related ILD. Among the patients who received both pleurodesis and EGFR-TKIs (n=23), 8 pa-
tients developed ILD. All of these patients were receiving EGFR-TKI therapy at the time of pleurodesis or
within 30 days after pleurodesis. In contrast, no cases of ILD were observed among the patients who stopped
EGFR-TKIs before pleurodesis or started EGFR-TKIs at more than 30 days after pleurodesis.
Conclusion ILD seemed to be a frequent complication of pleurodesis in patients using OK-432, especially
elderly patients and those who underwent pleurodesis while receiving EGFR-TKI therapy or who started
EGFR-TKI therapy within 30 days after pleurodesis.

Key words: interstitial lung disease, pleurodesis, malignant pleural effusion, OK-432, epidermal growth
factor receptor-tyrosine kinase inhibitor

(Intern Med 56: 1791-1797, 2017)
(DOI: 10.2169/internalmedicine.56.7464)

age and pleurodesis with the intrapleural instillation of
Introduction chemical agents to obliterate the pleural space and prevent
fluid accumulation is an effective therapeutic approach for
Malignant pleural effusion (MPE) is a common complica- controlling MPEs (2). Various chemical agents have been
tion in patients with advanced malignancies, especially lung used for pleurodesis. Talc, which is the standard sclerosing
cancer, and is associated with a dismal prognosis. Lung can- agent in many countries, has recently been approved for use
cer, which is the most common metastatic tumor of the in Japan. While the use of talc has been widely adopted
pleura, accounts for one-third of all MPEs (1). Tube drain- since its approval in Japan in 2013, the most frequently used


Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Japan and

Department of Radiology, Aichi Medical University School of Medicine, Japan
Received for publication March 23, 2016; Accepted for publication November 13, 2016
Correspondence to Dr. Akihito Kubo, kuboa@aichi-med-u.ac.jp

1791

4).5%) developed ILD. When there was discordance regarding the introduced into clinical oncology practice. ARDS was observed in 5. diluted in 100 mL of physiological saline. Pyrexia (10. performance 1792 . and the patient’s position was rotated for 2 fied as usual interstitial pneumonia (UIP) pattern (n=1) and hours. ILD occurred after pleurodesis in 8 (35%) either before pleurodesis or when the patient’s respiratory of the 23 patients who received EGFR-TKIs. ILD is diagnosed younger patients (6. Materials and Methods Statistical analysis Adverse events related to pleurodesis were evaluated ac- Study design cording to the National Cancer Institute Common Terminol- The medical records of consecutive patients who under. broad- tients who underwent pleurodesis with talc (6-9). or OK-432 plus MINO plus ex-smokers. were excluded from the study. Occasionally.22-19. and small cell carcinoma (n=4. 68% of the patients were male. Acute respiratory distress syn. Variables associated with vational study was approved by the institutional review pleurodesis-related ILD that had a p value of ! 0. 84 patients under- by thoracic drainage and the full expansion of the lung. version 4. The incidence of ILD after ILD and a diagnostic algorithm developed from the Ameri. tients (8%) of the 61 who did not receive EGFR-TKIs de- The internationally accepted criteria for the diagnosis of veloped ILD (p=0. and 14% had pre-existing CBDCA.0% of pa. The odds ratios (ORs) and accompanying 95% confi- School of Medicine between March 2008 and February dence intervals (CIs) of the categorical variables were esti- 2013 were retrospectively analyzed.7-20. 85. 11). A lack of response to these treatments supported a di- The present study investigated the incidence and risk fac. Cases 95% CI: 1. Cases of 95% CI: 1. OK-432 plus minocycline School of Medicine. The median age of the patients was 67 (MINO. (25. 11). determine the onset.9%). 13 patients (15. laboratory tests including blood tests. agnosis of ILD. 100 mg or 200 mg/body). After pleurodesis. Intern Med 56: 1791-1797. Af. and urine. No other factors. review results.82. including 5 patients with radiation suctioned at -10 mmHg. ogy Criteria for Adverse Events (NCI-CTCAE). univariate analysis were included in a multivariate logistic regression analysis.56. mated by a univariate analysis. went pleurodesis to control MPE in the Division of Respira- ter the instillation of OK-432 (0. The medical charts of all patients were reviewed in detail. ing sex. OK-432 plus carboplatin years. squamous cell carcinoma (n=5. and all cases of respiratory insufficiency were examined to Among the clinical factors. the reviewing physicians discussed the diag- nosis until they reached an agreement (10. and pulmonary embolism. The drainage tube was clamped after the removal of the effusion From March 2008 to February 2013. Fisher’s exact test was used to compare categorical vari- tory Medicine and Allergology.0%) are the most common complications of beroptic bronchoscopy with bronchial lavage and transbron- pleurodesis using talc (5). Aichi Medical University [KE]/kg.005). Results dwelling chest tube after being diagnosed with MPE.25 in the board of Aichi Medical University School of Medicine. maximum 10 KE/body).97. The tube was then unclamped. Briefly.9-9. older age (>67 years) (OR: 4. Pleurodesis All patients underwent thoracic drainage using an in. respectively. and non-UIP pattern (n=11. currence of ILD.3%). 2017 DOI: 10. Echocardiography and drome (ARDS) and acute interstitial lung disease (ILD) are contrast-enhanced thoracic CT were performed to discrimi- considered fatal complications of pleurodesis with talc.8%). allowed to drain. nosis. Aichi Medical University ables. The diagnosis of ILD 6. While ILD spectrum antibiotics and treatments for heart failure and/or may occur after pleurodesis with OK-432. and fi- and pain (14.2169/internalmedicine. pyogenes (OK-432) and tetracycline (3. pre-existing ILD. The tube was removed when the pneumonitis).08) and the use of epidermal growth factor acute ILD that occurred in the period between 1 year before receptor tyrosine kinase inhibitors (EGFR-TKIs) (OR: 5. and outcome. patients were adenocarcinoma (n=55. suspected cause. chest X.0. smoking history. the tube ILD (Table 1). 76% had lung cancer. The histological types of the 64 lung cancer drainage volume decreased to !100 mL per day. 67% were current or (CBDCA.2 Klinische Einheit units tory Medicine and Allergology. chial lung biopsy as necessary. includ- based on the onset of clinical symptoms and signs.6%) was significantly higher than the incidence in sus statement were used (10. while 5 pa- condition deteriorated.9) were significantly associated with the oc- in which computed tomography (CT) was not performed. its clinicopa.7%) (Table 2). This retrospective obser. 7. went pleurodesis to control MPE at the Division of Respira. In nate possible ILD from heart failure or other heart diseases previous studies.5%) microbiological cultures of sputum. pulmonary embolisms were administered to exclude a diag- thological characteristics have not been fully understood. viewed by 2 experienced physicians (1 radiologist and 1 trol MPE during a period in which talc had yet to be fully pulmonologist). and 1 year after pleurodesis were further investigated. blood. The 12 cases of pre-existing ILD were classi- was clamped. All of the cases were independently re- tors for ILD in patients who underwent pleurodesis to con. 300 mg/m2). pleurodesis among patients who were >67 years of age can Thoracic Society/European Respiratory Society consen.7464 agent is a pulverized product of heat-killed Streptococcus ray and CT findings.

CBDCA: carboplatin status (PS). Odds Ratio ILD (+) ILD (-) p value (95% CI) Total 13 71 Sex Male 8 49 1. ILD developed in 1 of the 432. TKI: tyrosine kinase inhibitor. or the success or 23 patients who underwent pleurodesis more than once. 10KE developed ILD (p=0.26-18. median years (range) 67 (39-85) Smoking status Current smoker 8 (10) Ex-smoker 48 (57) Never smoker 28 (33) Performance status 0-1 49 (58) 2-4 35 (42) Type of cancer Lung cancer 64 (76) Gastrointestinal cancer 5 (6) Genitourinary cancer 10 (13) Head and neck cancer 2 (2) Sarcoma 1 (1) Cancer of unknown primary 2 (2) Pre-existing ILD 12 (14) Comorbidities Diabetes mellitus 10 (12) Hypertension 23 (27) Coronary artery disease 7 (8) Cardiovascular disease 9 (11) Chronic obstructive pulmonary disease 7 (8) Liver cirrhosis 1 (1) Sclerosing agents for OK-432 52 (62) pleurodesis OK-432+MINO 22 (26) OK-432+CBDCA 7 (8) OK-432+MINO+CBDCA 3 (4) ILD: interstitial lung disease.78) 0.1 10 39 2.38-4.3 (0.68 Absent 12 60 EGFR-TKI Yes 8 15 5.005 treatment No 5 56 Smoking status Ever smoker 8 48 1.722). the number of OK-432 instillations.75 Never smoker 5 23 Performance 0.97 (1.43) 0. MINO: minocycline.22 status 2-4 3 32 Agents for OK-432 9 44 1.2169/internalmedicine.73 (0. and the sclerosing agents that were used for failure of pleurodesis: ILD occurred after pleurodesis in 2 of pleurodesis were associated with the development of the 19 patients who underwent pleurodesis using less than pleurodesis-related ILD.56. while 11 of the 65 patients who received ships between the occurrence of ILD and the dose of OK.7-20.41-4.74) 0. and 1793 .2 (0.08) 0.03 Older than 67 10 29 Pre-existing ILD Present 1 11 2. n (%) Total 84 (100) Sex Male 57 (68) Female 27 (32) Age.68) 0. 2017 DOI: 10.22 (0. CBDCA: carboplatin Table 2.7464 Table 1. EGFR: epidermal growth factor receptor. Intern Med 56: 1791-1797.34-4.39 (0. 10KE of OK-432.22-19. MINO: mi- nocycline.75 Female 5 22 Age 67 or younger 3 42 4.82 (1.9) 0. We found no significant relation. Subgroup Analysis of Risk Factors for ILD after Pleurodesis (n=84).37) 0.69-10.76 pleurodesis OK432+(MINO or CBDCA 4 27 or [MINO+CBDCA]) ILD: interstitial lung disease. Patient Characteristics.

and died on the whom it was successfully performed (p=0. EGFR-TKI treatment.15 0. PTX: paclitaxel. 23 patients received EGFR-TKI treatment.01). developed pleurodesis was not successful. DTX: docetaxel. The other patient started gefit- ate analysis revealed that age. or within 30 days after pleurodesis. and 12 of the 74 patients in ILD on the 89th day after pleurodesis. limiting self care ADL. PS: performance status. Never: never smoker.38 0. Ex-: ex-smoker. MPE. A multivari.101). grade 5: death 12 of the 61 patients who only underwent pleurodesis once smokers with lung adenocarcinoma. 8 developed ILD (67%. Figure). 1 Bilateral 4 187 5 61 Male LC (ad) Absent EGFR-TKI (erlotinib) Ex. in the lung ipsilat.51-31. notably. Two patients died of fore pleurodesis and none of the patients who started EGFR- ILD after pleurodesis. LC (sm): lung cancer (small cell carcinoma).2169/internalmedicine. LC (ad): lung cancer (adenocarcinoma). and 2 of the 3 (67%) patients who received erlotinib devel- eral to the site of pleurodesis in 6 patients.12 0. Ex. oxygen indicated. Both patients were elderly male ex. undergoing chemotherapy at the onset of ILD and. 2017 DOI: 10. Intern Med 56: 1791-1797. and with negative bacterial culture and cy. 1 Ipsilateral 4 42 6 83 Male LC (ad) Absent EGFR-TKI (gefitinib) Ex. 1 Ipsilateral 1 60 ILD: interstitial lung disease.5%) were receiving EGFR-TKI treatment. The risk 1794 . grade 2: symptomatic. There were no signs of ILD. 8 patients (61. 23rd day after pleurodesis. pleurodesis.1 / 2-3) 2.56. One other patient died on the 9th day after related ILD (Table 3). Six of the 9 (67%) patients who received gefitinib oped in the bilateral lungs of 6 patients. Type of Pre-exiting Chemotherapy Smoking No Age Sex PS Site of ILD CTCAE grade Interval cancer ILD at ILD onset status 1 69 Female LC (ad) Absent EGFR-TKI (gefitinib) Never 1 Bilateral 3 15 2 73 Male LC (ad) Absent EGFR-TKI (gefitinib) Ex.02 Performance status (0. medical intervention indicated. EGFR: epidermal growth factor receptor. 3 patients. TKIs at !30 days after pleurodesis developed ILD.02) were sig.9 1. who (p=0. VNR: vinorelbine. urgent intervention indicated. Among the 12 dominant cell fraction in which the proportion of lympho. and died on the 84th day after nificantly associated with the development of pleurodesis. Multivariate Analysis of Risk Factors for ILD after Pleurodesis.54 1.39-22. TKI: ty- rosine kinase inhibitor. supporting the diagnosis of ILD. Variable Odds Ratio 95% CI p value Age (>67 / ≤67) 6. Eleven patients were nal ulcers. 112th day after pleurodesis. 1 Ipsilateral 1 147 12 77 Female LC (ad) Absent . right lung cancer invading the esophagus.101). bronchoalveolar lavage (BAL) was performed for The patients who received EGFR-TKI treatment but ended it the differential diagnosis of the infection and lymphangitis before pleurodesis (n=9) or started EGFR-TKI at ! 30 days carcinomatosa. and in the con. intervention not indicated.19 CI: confidence interval. EGFR: epidermal growth factor receptor.59-13. tology results. CTCAE: common terminology criteria for adverse events. In In this study. 1 Contralateral 5 88 7 71 Male LC (ad) Absent EGFR-TKI (gefitinib) Ex. grade 4: life-threatening respiratory compromise.79 0.7464 Table 3. patients who received EGFR-TKIs at the time of pleurodesis cytes was >70%. A postmortem examination re- (Table 4). All BAL fluid showed a lymphocyte. TKI: tyrosine kinase inhibitor Table 4. Interval: interval between pleurodesis and ILD onset (days). ILD devel. after pleurodesis (n=2) did not develop ILD. and multiple liver metastases. ILD developed in 1 of the 10 patients in whom started gefitinib on the 18th day after pleurodesis.01 EGFR-TKI treatment (yes / no) 5. grade 3: severe symptoms. Characteristic of Patients who Developed ILD after Pleurodesis. PS. pleurodesis with OK-432. old inib on the 7th day after pleurodesis. developed ILD on the age (p=0. CBDCA: carboplatin. limiting instru- mental activity of daily life (ADL). oped ILD. and EGFR-TKI treatment (p=0. The median time from pleurodesis to the onset of vealed a massive gastrointestinal hemorrhage due to duode- ILD was 48 days (range. 11-187 days). None of the patients who ended EGFR-TKIs be- tralateral lung in 1 patient (Table 4). 1 Bilateral 2 48 8 63 Female LC (ad) Absent EGFR-TKI (erlotinib) Never 3 Bilateral 3 57 9 80 Male LC (ad) Present CBDCA+PTX Never 3 Bilateral 1 90 10 78 Male LC (ad) Absent VNR Ex. 1 Ipsilateral 5 22 3 51 Female LC (ad) Absent EGFR-TKI (gefitinib) Never 1 Ipsilateral 2 26 4 78 Female LC (ad) Absent EGFR-TKI (gefitinib) Ex. He received gefitinib for 5 days All of the patients who developed ILD had lung cancer (days 3-7 after pleurodesis). Never 2 Ipsilateral 3 11 13 83 Male LC (sm) Absent . clinical or diagnostic observations only. CTCAE grade 1: asymptomatic. One patient. 0 Bilateral 4 20 11 81 Male LC (ad) Absent DTX Ex.

The relationship is significant. the current study is the first to report an as- described in a small number of case reports.004). recognized that ILD is more common in Japan than in other set of ILD and EGFR-TKI therapy in patients who received countries. ter pleurodesis (OR: 43.5%) occurred among 26 patients who underwent therapy and developed ILD after pleurodesis. 95% CI: 2. p=0. While no ILD was reported in the 34 cant risk factors (other than EGFR-TKI use and older age) patients who received OK-432 in a phase II trial of for ILD. developed ILD.41. developed fatal ILD. 2017 DOI: 10. and 6 patients died of ILD (33%). as a sclerosing agent. A large-scale prospective study on gefitinib- pleurodesis to control MPE. ILD and pleurodesis in patients who were treated with EGFR-TKIs (n=23). 2 (25%) of these patients died tors. of ILD was significantly higher in patients who received related ILD was described in 18 patients in 8 reports. Overall.7464 Figure. tion after the diagnosis of NSCLC.05-920. flammation of the pleura and lung after pleurodesis using 61. poor PS. It is pleurodesis. pleurodesis.2169/internalmedicine. Within the scope of our lit- nized to be a serious complication. and 34. induced ILD in Japan revealed that the risk of developing Notably. Two major risk factors for TKI-related ILD is the reduced volume of the normal lung ILD were identified: EGFR-TKI therapy (odds ratios: 5. pre-existing ILD. The high prevalence Discussion (15. who underwent EGFR-TKI therapy developed ILD after ILD is a major adverse event of EGFR-TKI therapy. who was undergoing gefitinib treatment at pleurodesis. reduced normal lung on All of the patients in the current study received OK-432 CT. 66. Ishimoto reported that 3 cases of ILD existing ILD among the patients who received EGFR-TKI (11. ILD occurred in 5 of the 61 (8%) patients who did who underwent pleurodesis to control MPE.54) on CT (<50%) (10). In total.7% of the patients who received EGFR-TKI acute ILD was mainly greater in the first 4 weeks after the therapy at the time of pleurodesis or within 30 days after initiation of gefitinib. One patient.90)..8% of patients ume. the incidence of not receive EGFR-TKIs. increasing the risk of EGFR-TKI-related ILD. Intern Med 56: 1791-1797. mostly EGFR-TKIs at the time of pleurodesis or within 30 days af. It should also be noted that none had pre- (NSCLC) (4). patients receiving EGFR-TKIs. with OK-432 (n=17). The study further defined the risk fac- pleurodesis. most of which sociation between pleurodesis-related ILD and the use of were conference abstracts that were written in the Japanese EGFR-TKIs. smoking. which may be attributable to the small sample size pleurodesis for MPE from non-small cell lung cancer of the study.5%) of ILD in the present study might be related with the use of EGFR-TKIs. We hypothesize that the chemical in- and older age at pleurodesis (odds ratio: 6. study. the patients who were treated with EGFR-TKIs were 1795 . some received additional minocycline Pleurodesis has not been reported as a risk factor for ILD in and carboplatin. and it has mostly been erature search. Pleurodesis-related ILD has been recog. which include older age.4.5% of the patients who developed ILD after pleurodesis OK-432 may damage the normal lung and reduce its vol- had undergone EGFR-TKI therapy.5%. The present study failed to identify any signifi- language (Table 5). In the present pleurodesis using OK-432 (Table 5). and concurrent cardiac disease (10).56. Similarly to the report of Ishimoto In this retrospective analysis of 84 consecutive patients et al. short dura- of ILD. One of the risk factors for EGFR- ILD after pleurodesis was 15. suggesting a strong relationship between the on.

It is now cles of <10 μm in size are removed). particularly for elderly patients. Kuzniar et the period of our retrospective study. and the ing lung diseases. Although acute ILD has been attributed to the talc therapy alone (without pleurodesis). and the clinical and laboratory ex- Japan.7464 Table 5. mostly never smokers or light smokers and had no underly. Older patients have study. died of ILD (Table 4 and Figure). PT (1) CDDP+OK-432 (1). PT: pneumothorax. to elucidate the incidence and clini. 41: 272. days before pleurodesis were significant risk factors for ment with EGFR-TKIs. [3] Annals of the Japanese Respiratory Society 1999. ( ): no of patients. differential diagnoses were raised. seems be a preferable particle size. 37: 276. 16). [6] Japanese Journal of Lung Cancer 2008. 2 elderly patients. 1: 187-194 (in Japanese). Pleural disease and Chemotherapy ≤ 30 days n Sclerosis agents Outcome reference cancer type interval from pleurodesis 3* MPE (3) LC (3) OK-432 (3) CBDCA+VP-16+VCR (1) Died (1) [1][2] NR (2) Improved (2) 4 MPE (3).2169/internalmedicine. 2017 DOI: 10. 95% CI: 1. highlighting the potential risk of combin. reported that the presence of peripheral edema. including patients with MPE (12). chemotherapy in NSCLC (10). However. and after pleurodesis was restricted to a detailed chart re- 15. However. several signs in high- cal features of pleurodesis-related ILD.56. Kudoh et al. OR: 4. acute ILD after surgical pleurodesis with talc (7). VP-16: etoposide. [8] Annals of the Japanese Respiratory Society 2013. the use of “graded” talc (in which most parti- treatment option for reducing the risk of ILD. the tive diagnosis of acute ILD retrospectively when multiple mortality due to ILD after pleurodesis and EGFR-TKI ther. Considering the ef. This has recently been approved in tions were often serious. In the present study. It was challenging to make a defini- EGFR-TKIs). MPE: malignant pleural effusion. VCR: vincristine. and chemotherapy within 14 many patients underwent pleurodesis before starting treat. [1] Respiratory Molecular Medicine 1997. Abstracts in Japanese from the meeting proceeding of [2] Japanese Journal of Lung Cancer 2001. LC: lung cancer. talc-related ILD in Japan. 17). lung infection. EGFR-TKI ing talc. This was particularly evi- apy was 25%. it was not well known al. cases of pleurodesis-related ILD can prevent the recurrence of MPE (13). CDDP (1) NR (4) Died (2) [3] LC (3). and lym- In many countries. acute ILD and fectiveness of EGFR-TKIs in the treatment of EGFR-mutant ARDS are the most serious complications of pleurodesis us- lung cancer. during have even been reported with graded talc (7. 41: 547. PT (1) OK-432 (4) NR (4) Improved (4) [8] LC (4) 18 MPE (15). supple- that MPE could be controlled by EGFR-TKI alone. and after pleurodesis in pleu. talc is used as the standard agent in phangitis carcinomatosa. agnosed from pulmonary edema. In many countries. The indications for pleurodesis need to be dent in cases in which acute ILD had to be differentially di- carefully considered. 2: 321. results cannot directly be extrapolated to the potential risk of ing EGFR-TKI therapy and pleurodesis. has been regarded as widely accepted that EGFR-TKI alone (without pleurodesis) relatively safe (15. PT (2) OK-432 (15) CBDCA+VP-16+VCR (1) Died (6) Chylothorax (1) OK432 combined (2) Gefitinib (1) Improved (12) LC (17). [5] Journal of the Japan Society for Respiratory Endoscopy 2010. sis were therefore limited. accordingly. we suggest that patients who receive pleurodesis with been reported to be at a higher risk of ILD regardless of the talc should be closely monitored. thus.21). All of the cases in resolution computed tomography (HRCT) may be helpful in 1796 . Reports of ILD after Pleurodesis. CBDCA: carboplatin. 48: 558. most of which are derived from the fact that it was a rela- ral mesothelioma (14). Consider- It was also shown that elderly patients (>67 years) were ing the unexpectedly high prevalence of ILD in the present at higher risk of ILD after pleurodesis. DXR: doxorubi- cin. [4] Japanese Journal of Lung Cancer 2001. 51: 282. [7] Japanese Journal of Lung Cancer 2011. OK-432 (1) Improved (2) 1 MPE (1) LC (1) OK-432 (1) NR (1) Improved (1) [4] 5 MPE (5) LC (5) OK-432 (5) Gefitinib (1) Died (2) [5][6] NR (4) Improved (3) 1 Chylothorax (1) OK-432 (1) NR (1) Died (1) [7] LC (1) 4 MPE (3). NR (1) CDDP (1) NR (16) ILD: interstitial lung disease. also reported that the tively small retrospective study that was performed in a sin- rate of mortality due to ILD was significantly higher in gle institute.33. The assessment of the clinical course before older patients (!65 years of age. NR: not reported. The present study was conducted in our institute at aminations that are necessary to achieve an accurate diagno- the introduction of talc. a 73-year-old view. NR (1) DXR+OK-432 (1). administration of EGFR-TKI therapy or cytotoxic systemic The present study is associated with some limitations. and mentary oxygen requirement.49. 32: 198. three developed ILD. this study received OK-432 as a sclerosing agent. the information largely came from the re- man and an 83-year-old man (both of whom received cords of clinical care. Intern Med 56: 1791-1797. because the patients’ general condi- sclerotherapy for MPE. *In 26 patients who underwent pleurodesis using OK-432.

Interstitial lung disease in sary discuss a diagnosis. J Clin Oncol 9: 313-319. Kuhlman JE. et al. Intern Med 56: 1791-1797.html 1797 .2169/internalmedicine. Care Med 170: 377-382. Mineshita M. Computed tomography of of three intrapleural therapy regimens for the management of ma. talc pleurodesis. Kelly MG. Tian G. Florence MG. 13. platin and cytarabine in the management of malignant pleural effu. Yoshida K. view the details of this license. Ann Thorac Surg 82: 1976- 1981. Intrapleural cis. Rehse DH. Ishida A. Figlin R. Blum MG. Curr Drug Discov Technol 13: 68-76. Takifuji N. 2012. Society (ATS). Gemba K. Nojiri S. Japanese patients with lung cancer: a cohort and nested case- nosed as accurately as possible. 2000. 2006. Inoue T. Randomized trials describing lung inflammation after fusions. dergoing operative talc pleurodesis. when neces- 10. Browne J. Soler P. Sedrakyan A. inflation-fixed lungs: the beaded septum sign of pulmonary metas- lignant pleural effusion in previously untreated non-small cell lung tases. American Thoracic Society. Chastre J. June 2001. further studies are warranted to confirm the present adopted by the ATS board of directors. rather than lymphangitis carcinomatosa.or. with Tarceva therapy. Ann Intern Med 120: 56-64. Oncol Rep 27: 880-890. Godwin D. This joint statement of the American Thoracic study were based on the experience at a single institute. Nishiwaki Y. Tan C. cancer: JCOG 9515. Mutlu GM. and suggest ILD. Walker-Renard PB. Eur J Intern Med 18: 611. Sugiura T. ceiving EGFR-TKIs. Pharmacoepidemiol Drug Saf 20: 643-652. 1989. EGFR mutations predict a favorable present study suggests the need for a cautious approach to outcome for malignant pleural effusion of lung adenocarcinoma pleurodesis. 2013. 2008. Hedley EL. Gonzalez AV. this study was another limitation. RJ. it did not can Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Inter- reach statistical significance. that having 2 experienced physicians (1 pulmonologist and 1 9. The Internal Medicine is an Open Access article distributed under the Creative Miyazawa T. Am J Respir Crit Care Med In conclusion. Wan Y. Aoe K. Ren H. Pre- Ⓒ 2017 The Japanese Society of Internal Medicine http://www. 7. 1994. Talc pleurodesis for the management of malignant Commons Attribution-NonCommercial-NoDerivatives 4. et al. The small sample size of control study. of malignant pleural effusion (MPE) in lung adenocarcinoma. pleurodesis with talc of varying particle size. and the European Respiratory Society (ERS) was thus. Rusch VW. Nishine H. a systematic review. Intern Med 52: 1173-1176. Kudoh S. 16. Guo H. Gaudichet A. Hruban RH. et al. Chest 137: 1375-1381. Respiratory failure following by-nc-nd/4. We believe Chest 86: 795-797. Piantadosi S. may suggest lymphangitis carcinomatosa (18). Acute and the appearance of the beaded sign or a beaded septum pneumonitis with bilateral pleural effusion after talc pleurodesis. please visit (https://creativecommons. especially in elderly patients and patients re.jp/imonline/index. Vaughan LM. June 2001 and by the ERS findings in other settings. Verma A. Sahn SA. Kasibowska-Kuzniar K. 8. Aye RW. Pengelly G. 12. 2004. Gleeson FV. Eur J Cardiothorac Surg 29: 829-838. Bezwada V. 2017 DOI: 10. 2016. Chemical pleurodesis 17. however. To pleural effusions in Japan. Nakamura M.org/licenses/ 6. and who could. Lee YC. Am J Respir Crit 2. Chugai. 3. Am J Respir Crit Care Med 162: 1987-2001. 4. 2006. 2011. Kuzniar TJ.56. the 165: 277-304. Acute respiratory distress syndrome (ARDS) secondary for malignant pleural effusions. to talc pleurodesis. despite the above-described limitations. Ameri- risk factor for the development of ILD. 2010. et al. Bouchama A. Swift S. The evidence sions: a Lung Cancer Study Group trial. Maskell NA. References 15. 14. Villanueva AG. on the effectiveness of management for malignant pleural effusion: 1991. Akihito Kubo: Honoraria.0 International License. 5. Lee YW. Gibert C. Lung Cancer 58: 362-368. 2002. Kato H. the observations in this stitial Pneumonias. evaluations and chart records. et al. American Thoracic Society Management of malignant pleural ef. Can EGFR-Tyrosine Kinase Inhibitors (TKI) alone without talc pleurodesis prevent recurrence Author’s disclosure of potential Conflicts of Interest (COI). Chopra A. 1984. European Respiratory Society. Am J Surg 177: 437-440. Randomized phase II trial 18.7464 the discrimination of ILD: the dominance of pure ground dictors of acute lung injury and severe hypoxemia in patients un- glass opacities may correspond to diffuse alveolar damage. et al. Lung in- diagnostic radiologist) independently review the radiological jury following thoracoscopic talc insufflation: experience of a sin- gle North American center. Executive Committee. Beamis JF Jr. 2007.0/). 1999. Incidence of interstitial lung dis- ease in patients with mesothelioma in the west part of Japan.naika. Treasure T. meant that the cases were diag. Third. Am J Respir Crit Care Med 177: 1348-1357. A poor PS tended to be a 11. 2007. Davies 1. J Comput Assist Tomogr 13: 411-416.