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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 2  |  Page : 324-328

Chyle test is not a valuable laboratory index in identifying chylothorax after pulmonary resection and lymph node dissection for primary non-small cell lung cancer


1 Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, People's Republic of China
2 Department of Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, People's Republic of China

Date of Web Publication1-Apr-2019

Correspondence Address:
Prof. Zhongmin Peng
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong Province
People's Republic of China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_249_18

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 > Abstract 


Objective: Chyle test is widely used to identify chylothorax after pulmonary resection and lymph node dissection for primary non-small cell lung cancer (NSCLC). Low accuracy of chyle test in identifying chylothorax is rarely reported. This observational study was designed to identify the diagnostic value of chyle test.
Patients and Methods: From September 2016 to March 2017, 185 consecutive patients either suspected or histologically documented lung cancer were screened for this observational study. Except exclusion, 108 patients were eligible for further analysis. Daily chest-tube output as well as the postoperative day of chest tube removal was documented. Chyle test was analyzed with 108 cases, and the results were blinded to the thoracic surgeons. Chest tube was timely removed regardless of the results of chyle test. A high-output pleural effusion and an associated change in quality of the pleural fluid, from serous to milky yellowish after normal diet, led to the diagnosis of chylothorax. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of chyle test in identifying chylothorax were calculated.
Results: Of 108 patients, 4 (3.7%) were observed with chylothorax after pulmonary resection and lymph node dissection for primary NSCLC. Postoperative chylothorax was conservatively managed in three patients and chest tubes were removed 12 days (from 10 to 16) after surgery. Failed in conservative treatment, one patient underwent thoracic duct ligation performed by video-assisted thoracic surgery. For patients without chylothorax, the median day of chest tube removal was postoperative day 4. Among the 108 patients, 75.9% (82/108) was found with a positive chyle test result, of which 95.1% (78/82) was false positive in identifying chylothorax. The sensitivity and specificity of chyle test in identifying chylothorax were 100% and 25%, respectively. The positive predictive value, negative predictive value, and accuracy of chyle test for chylothorax diagnosis were 4.9%, 100%, and 27.8%, respectively.
Conclusions: It was suggested that the specificity and accuracy of chyle test in identifying chylothorax were relatively low. Chyle test is not a good laboratory index in identifying chylothorax. With highly positive result, chyle test should not preclude the removal of chest tube in patients after pulmonary resection and lymph node dissection for primary NSCLC.

Keywords: Chyle test, chylothorax, non-small cell lung cancer, pleural fluid


How to cite this article:
Wang H, Gao J, Zhang R, Xie H, Peng Z. Chyle test is not a valuable laboratory index in identifying chylothorax after pulmonary resection and lymph node dissection for primary non-small cell lung cancer. J Can Res Ther 2019;15:324-8

How to cite this URL:
Wang H, Gao J, Zhang R, Xie H, Peng Z. Chyle test is not a valuable laboratory index in identifying chylothorax after pulmonary resection and lymph node dissection for primary non-small cell lung cancer. J Can Res Ther [serial online] 2019 [cited 2019 Apr 21];15:324-8. Available from: http://www.cancerjournal.net/text.asp?2019/15/2/324/255087




 > Introduction Top


The enhanced recovery after surgery (ERAS) concept was first introduced for patient care by Kehlet and Wilmore in 1990.[1] ERAS is primarily developed to promote postoperative recovery in patients undergoing colonic surgery. In recent years, more and more attention is paid to thoracic surgeons.[2],[3] For thoracic surgery patients, ERAS protocols were established to faster mobilization, alleviate postoperative pain, decrease complications, and save hospitalization costs.[4],[5] Early removal of chest tube is one of the critical elements of ERAS.

Thoracic surgeons made more clinical decisions about the management of patients' chest tube than any other clinical problem.[6],[7] Delayed chest tube removal induces aggravation of pain, patients' immobilization. It can also increase the risk of infection. At the same time, delayed chest tube removal prolongs the length of stay and increases hospitalization costs.[8] Therefore, it is of great potential economic value for early chest tube removal.

Chylothorax after pulmonary resection and lymph node dissection for primary non-small cell lung cancer (NSCLC) was found a rare complication, with an incidence rate of approximately 1.4%–4%.[9],[10],[11] To remove the chest tube, the pleural fluid should be nonchylous.[6] In other words, chylothorax is one of the contraindications of chest tube removal. Chylothorax is defined as leakage of lymphatic fluid enriched with chylomicrons and lipids into the thorax.[12] There are no standard criteria for the diagnosis of chylothorax. The definite diagnosis for diagnosis of chylothorax depends on the combination of clinical manifestation, laboratory examination, and radiography. With microscopic examination, fat globules and chylomicrons in the pleural fluid are extracted by ethanol and then stained with Sudan III, Chyle test is widely used to identify chylothorax.[13],[14],[15],[16] However, it was found that the diagnostic specificity and accuracy of chyle test for chylothorax diagnosis clinically are relatively lower than theoretically. This observational study is to elucidate the diagnostic value of chyle test in identifying chylothorax in patients with NSCLC after pulmonary resection and lymph node dissection. This observational study was tried to clarify that a positive result of chyle test should not preclude the removal of chest tube.


 > Patients and Methods Top


Patient selection

From September 2016 to March 2017, 185 consecutive patients with suspected or histologically documented lung cancer were screened for this observational study. Patients aged 18–75 years were included, with an Eastern Cooperative Oncology Group performance status of 0–2 but distant metastasis. Any patients who underwent wedge resection, received neoadjuvant chemotherapy, or had a medical history of chest operation were excluded. Patients were also excluded with a benign postoperative pathology or with an air leak of more than 5 days or who had underwent reoperation due to hemorrhage. Finally, 108 patients were eligible for further analysis.

In accordance with the Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects, this study was approved by the Regional Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong University. All patients were required to sign informed consent and authorized the use of their personal information for research purposes.

Surgical technique

Patients underwent segmentectomy, lobectomy, or pneumonectomy for NSCLC. Lymph node stations were dissected for tumors on the right were 2R, 4R, 7, 9R, 10R, and 11R. For tumors on the left, stations 5, 6, 7, 9 L, 10 L, and 11 L were dissected.[17] After hemostasis was confirmed, a 28F chest tube (Jinan Chensheng Medical Silicone Products Co. Ltd, Jinan, China) was placed in the apical and posterior pleural space through the wound on the seventh rib of the midaxillary line. Pathological staging was according to the 8th edition of the American Joint Committee on Cancer–International Association for the Study of Lung Cancer staging classifications.[18]

Chest tube management and chylothorax

Daily chest-tube output was documented. Chest tube was removed if: (1) no active hemorrhage; (2) no air leak; (3) no atelectasis on postoperative chest radiograph; (4) drainage volume was <200 ml within 24 h, or the quality of the pleural fluid did not change from serous to milky yellowish to normal diet.

A high-output pleural effusion and an associated change in quality of the pleural fluid, from serous to milky yellowish after normal diet, led to the diagnosis of chylothorax.[19]

Chyle test

Two to 3 days after surgery, pleural fluid was obtained from the chest tube. First, the pleural fluid was dissolved with Sudan III in 70% ethanol pleural fluid to make a sated solution. Then, 5-ml pleural fluid was put into 3-ml ethanol. It was mixed for several minutes and centrifuged at 2000 rpm for 5 min. Next, the intermediate layer was absorbed and mixed it with Sudan III. On microscopic examination, the presence of red fat globules was diagnostic. Results of the chyle test were blinded to the thoracic surgeons.

Statistical analysis

Statistical analysis was carried out with the software SPSS 19.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as the mean ± standard deviation and compared between groups with Students t-test. Categorical variables were compared by either the Chi-square or Fisher's exact test. P < 0.05 was considered statistically significant.


 > Results Top


Demographic data

The overall demographic data of the 108 patients are presented in [Table 1]. Sex of the patients was composed of 45 women and 63 men. Sixty-two (57.4%) patients were asymptomatic at presentation. The median patient age was 59 years (range: 34–76); 12 patients were aged 70 years or older. Smoking history was present in 53 patients (49.1%). Thirty-eight (35.2%) patients were found with family history of cancer. The mean forced expiratory volume in 1 s was 2.6 L (1.24–4.56 L). The mean diffusing capacity of lung for carbon monoxide was 77.3% of predicted (49.1%–113.6%). The comorbidity of this series included 6 patients with chronic obstructive pulmonary disease, 26 patients with high blood pressure, 6 patients with coronary heart disease, and 9 patients with diabetes mellitus [Table 1].
Table 1: Demographic characteristics of the 108 patients

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Perioperative data

Video-assisted thoracoscopic surgery (VATS) was successfully performed in 70.4% of the patients. Four conversions were to open thoracotomy: 2 cases had bleeding, 1 case had density of adhesions, and 1 case had dense hilar lymphadenopathy.

The treatment modality was lobectomy in 82 patients (75.9%), bilobectomy in 5 (4.6%), segmentectomy in 7 (6.5%), pneumonectomy in 9 (8.3%), and lobectomy plus segmentectomy in 5 (4.6%). The distribution of the segmentectomies was as follows: 1 patient apical segment of the right upper lobe, 1 patient anterior segment of the right upper lobe, 2 patients posterior segment of the right upper lobe, 2 patients superior segment of the right lower lobe, and 1 patient apical segment of the left upper lobe. Five patients underwent left pneumonectomy and four patients underwent right pneumonectomy. The mean operative time and bleeding volume were 141.8 ± 42.3 min and 178.2 ± 220.1 ml, respectively.

The pathologic analysis included 78 adenocarcinoma patients, 24 squamous cell carcinoma patients, 3 large-cell neuroendocrine carcinoma patients, 2 carcinoid patients, and only 1 NSCLC patient. The pathological lymph node status was N0 in 76 patients, N1 in 10, and N2 in 22. Pathological staging revealed the following: Stage I in 68 patients, Stage II in 14, Stage III in 24, and Stage IV in 2 patients (1 solitary adrenal metastasis and 1 solitary brain metastasis).

No postoperative mortality was observed.

Chest drainage and chyle test

Chylothorax after pulmonary resection and lymph node dissection for primary NSCLC was observed in 4 (3.7%) patients. Postoperative chylothorax was managed conservatively in three patients and their chest tubes were removed 12 days[10],[11],[12],[13],[14],[15],[16] after surgery. One patient failed in conservative treatment and underwent thoracic duct ligation performed by VATS. For patients without chylothorax, the median day of chest tube removal was postoperative day 4. The median chest-tube output during the first 4 postoperative days, for all 108 patients, was divided into two groups (chylothorax and nonchylothorax) [Figure 1].
Figure 1: Median chest-tube output during the first 4 postoperative days for all 108 patients, divided into two groups by daily output: chylothorax and nonchylothorax

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Chyle test was analyzed with 108 cases. Patients' demographic data and univariate association with chyle test are summarized in [Table 2]. Among the 108 patients in the study, 75.9% (82/108) were found with a positive chyle test result [Figure 2], of which 95.1% (78/82) were found with false-positive result [Table 3].
Table 2: Demographic data according to the result of chyle test for the 108 patients

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Figure 2: Chyle test after pulmonary resection and lymph node dissection for primary non-small cell lung cancer (a) positive result, ×2000 (b) negative result, ×2000

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Table 3: The sensitivity and specificity of chyle test in identifying chylothorax

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In identifying chylothorax, the sensitivity and specificity of chyle test were 100% and 25%, respectively. The positive predictive value, negative predictive value, and accuracy of chyle test for chylothorax diagnosis were 4.9%, 100%, and 27.8%, respectively [Table 3].


 > Discussion Top


Chylothorax after pulmonary resection delays chest tube removal and induces aggravation of pain to patients with NSCLC. The early removal of a chest tube reduces pain and improves ventilatory function.[20] The earlier removal of chest tubes would accelerate the postoperative recovery.[21] During the postoperative course, the diagnosis of chylothorax is based on clinical observation of quantity, quality of chest drain output, laboratory examination, and radiography. Previously, it was thought that chyle test was a reasonable and acceptable method in chylothorax diagnosis. Once a positive chyle test exists, a thoracic surgeon dare not remove the chest tube even drainage volume is low. However, in this study, it was indicated that the specificity of chyle test in identifying chylothorax is only 25% even with a high sensitivity of 100% and accuracy of just 27.8%. Therefore, it is recommended that chest tube can be removed safely regardless of the results of chyle test. The diagnosis of chylothorax mainly depends on high-output pleural effusion as well as associated change in quality of the pleural fluid, from serous to milky yellowish after normal diet.

Initial conservative therapy was applied to all cases of chylothorax with expected excellent outcomes. Conservative treatment aims to reduce chyle production through diet control and relieve symptoms by draining the chylous effusion from the thoracic cavity.[22] With this method, lymphatic vessel rupture will probably close spontaneously as well as thoracic duct rupture.[23] Patients who fail in conservative treatment are good surgical candidates. Those with the site of the leak well identified, thoracic duct ligation performed by VATS is the gold standard surgical approach with less postoperative pain and quicker recovery and shorter hospital stay.[24]

The incidence of chylothorax in this study was 3.7%, which is in accordance with previous reports. In a study by Takuwa et al.,[10] 1580 patients underwent lobectomy or greater resection and systematic mediastinal lymph node dissection for primary lung cancer. Postoperative chylothorax was detected in 37 patients (2.3%), of which 31 cases (84%) received conservative treatment and 6 patients (16%) underwent reoperation. The author recommended that surgical intervention was necessary if the chest tube drainage during the first 24 h after the initiation of a low-fat diet was >500 ml. It was reported that 2838 patients underwent pulmonary resection with mediastinal lymph node dissection by one surgeon.[9] The incidence rate of chylothorax was 1.4. It was higher in patients with pathologic N2 disease and those who underwent robotic resection. Nonoperative therapy was almost always effective. Of four chylothorax patients in this study, three received conservative treatment and their chest tubes were removed 12 days (range 10–16) after surgery.

There are two main causes for a chylothorax after lung resection. The first is injury to the main thoracic duct. The other is laceration of a lateral branch of the duct or a leaking lymph node basin. The course of thoracic duct is aberrant with around 45% of the patients.[16] Branches of the thoracic duct were vulnerable when lymph nodes of the hilum and mediastinum were dissected. The low specificity and high sensitivity of chyle test might well explain in identifying chylothorax. Unfortunately, the chyle test is just a qualitative index. Unlike the quantitative index, we could not find a threshold value to identify chylothorax.

Admittedly, there are also some limitations in this study. Sample size obtained for the study is relatively small, and there are only four cases of chylothorax. Results should be validated in larger sample patient cohorts. What is more, the triglyceride level of pleural fluid was undetected.


 > Conclusions Top


Although the sensitivity of chyle test in identifying chylothorax was as high as 100%, both specificity and accuracy were relatively low. Chyle test is not a good laboratory index to identify chylothorax. A positive result of chyle test should not preclude the removal of chest tube in patients after pulmonary resection and lymph node dissection for primary NSCLC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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