Cough, Lung Cancer, Vagus Nerve Injuries
Conditions
Brief summary
Lung cancer is the leading cause of cancer death worldwide. Surgical resection is the main treatment for resectable non-small-cell lung cancer (NSCLC), and lobectomy with systemic mediastinal lymph node dissection is the standard surgical method. However, a significant number of patients experience postoperative chronic cough; it is observed in about 60% of patients during the first year of outpatient clinic follow-up, and persistently lasts in about 24.7-50% during the 5 year follow-up period. Several studies showed the association between vagus nerve and chronic cough. The bronchopulmonary vagal afferent C-fibers are responsible for cough, chest tightness and reflex bronchoconstrictions. It is expected that during the mediastinal lymph node dissection, the inevitable injuries to the pulmonary branch of vagus nerve is largely responsible for development of chronic cough. In other words, preservation of pulmonary branch of vagus nerve may reduce the incidence of chronic cough and relevant detrimental effects on quality of life. Therefore, this prospective, randomized and controlled clinical study, aims to evaluate the effect of vagus nerve preservation on postoperative chronic cough in patients undergoing lobectomy with mediastinal lymph node dissection. In addition, the feasibility and oncologic safety of preserving pulmonary branch of vagus nerve during mediastinal lymph node dissection with minimally invasive surgery compared with conventional mediastinal lymph node dissection with minimally invasive surgery will also be investigated. This trial will provide a new basis for oncologically feasible, safe and effective new surgical technique for mediastinal lymph node dissection in patients with early lung cancer undergoing minimally invasive surgery. Furthermore, the preventive effect of vagus nerve preservation on incidence of chronic cough will be objectively be proven and thus help to broaden the current knowledge of the role of vagus nerve and postoperative chronic cough.
Interventions
PROCEDUREPulmonary branch of vagus nerve preserved
During the mediastinal lymph node dissection using minimally invasive surgery, efforts to preserve the pulmonary branch of vagus nerve is made.
PROCEDUREPulmonary branch of vagus nerve not preserved
During the mediastinal lymph node dissection using minimally invasive surgery, efforts to preserve the pulmonary branch of vagus nerve is not made/ can be severed.
Sponsors
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
214 patients will be divided into two groups. 1. Control group (N=107): Effort to preserve the pulmonary branch of vagus nerve preservation is not made in this group during mediastinal lymph node dissection 2. Treatment group (N=107): Effort to preserve the pulmonary branch of vagus nerve preservation is made in this group during mediastinal lymph node dissection
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects clearly understand the purpose of the study, are willing and able to comply with the requirements to complete the study, and can sign the informed consent. 2. Clinically suspicious of non-small cell lung cancer or tissue confirmed preoperatively 3. Clinical stage T1-3/N0-1/M0 4. Preoperative ECOG performance status 0-1 5. Preoperative ASA class I-III 6. Preoperative pulmonary function test FEV1 ≥ 60%, DLCO ≥ 60% 7. Patients expected to achieve R0 (complete resection) via simple lobectomy and mediastinal lymph node dissection
Exclusion criteria
1. Patients who smoked within 2 weeks prior to operation 2. Patients who received antitussives and expectorants 2 weeks prior to operation 3. Patients who are pregnant or breast feeding 4. Patients with severe or uncontrolled psychological disorders 5. Patients with severe pulmonary adhesion 6. Patients who are ineligible for minimally invasive surgery; thoracotomy conversion 7. Patients diagnosed with other malignancies within 2 years prior to operation 8. Patients who received chemotherapy or radiotherapy within 6 months prior to operation 9. Patients suspicious of clinical N2 or received neoadjuvant therapy prior to operation 10. Patients with cough-related diseases; COPD, asthma, ILD, GERD 11. Patients suspicious of lymph node metastasis/invasion around vagus nerve during the preoperative clinical staging evaluation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Qualitative measurement of postoperative cough | Preoperative day | Cough Visual Analog Scale (VAS) will be used for survey. The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough. |
| Quantitative measurement of postoperative cough | Preoperative day | The Korean version of the Leicester Cough Questionnaire will be used for survey. Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum TRPA1, TRPV1, bradykinin, PGE2 measurements | Preoperative day | Measurement of TRPA1 (ng/mL), TRPV1 (ng/mL), bradykinin (pg/mL), PGE2 (pg/mL) (released from C-fibers) via enzyme-linked immunosorbent assay (ELISA) test to quantitatively measure the injures of the vagus nerve during the mediastinal lymph node dissection. |
| Pulmonary function test | Preoperative day | Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function |
| Incidence of postoperative pulmonary complications, hospital stay and readmission, ICU care | from admission for operation to until the date of first documented postoperative complication or readmission, whichever came first), assessed up to 30 days | — |
| Histopathologic review of the total number of mediastinal lymph node dissected | through study completion, an average of 1 year | Total number of dissected mediastinal lymph nodes and metastatic lymph nodes will be analyzed. Patient's preoperative clinical N stage and pathologic N stage will be compared; if pathologic N stage is higher than that of the clinical N stage, it will be considered as nodal upstaging. |
Countries
South Korea
Contacts
Primary ContactKwhanmien Kim, MD. PhD
Outcome results
None listed