Patient Selection
A retrospective analysis was performed, a total of 92 patients with chronic lung diseases underwent thoracoscopic segemtectomy with near-infrared fluorescence (NIF) imaging. The first near-infrared fluorescence guided thoracoscopic segmentectomy was performed in September 2017, the first thoracoscopic segmentectomy using inflation-deflation method was performed in March 2014, and the initial 30 cases were not included due to the learning curve effect(6), a total of 149 patients with chronic lung diseases were included in control group. All surgeries were performed by highly-experienced experts in this specialized procedure(Highly experienced surgeon was defined as surgeon achieved more than 200 cases of segmentectomy, including sub-segmentectomy and combined segmentectomy.). All surgeries were completed through one single incision. Consultants in our department all agreed that either technique was suitable for each patient. Cases with conversion to thoracotomy or lobectomy were excluded.
This study for the application of thoracoscopic segmentectomy and near-infrared fluorescence imaging was approved by by the institutional review board at Nanjing Chest Hospital(number of the ethics approval: 2014-KL002-02 for uniportal thoracoscopic segmentectomy, 2017-KL-002-03 for near-infrared fluorescence guided thoracoscopic segmentectomy), written informed consent about operative techniques and to the data-use agreement was obtained from all patients before surgery.
The inclusion criteria for NIF-VATS or ID-VATS segmentectomy in patients with chronic lung diseases: Pulmonary nodules with a diameter of less than or equal to 2 cm in thin-slice chest CT and have at least one of the following characteristics: 1. adenocarcinoma in situ, 2 composition of ground glass appearance is greater than or equal to 50%, 3. lesion doubling time is greater than or equal to 400 d; Based on preoperative CT findings, patients with comorbid COPD(emphysema or chronic bronchitis), ILD(idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia(IP), or CPFE(Combined pulmonary fibrosis and emphysema).
Exclusion criteria were pulmonary nodules that cannot be removed by segmental pulmonary resection, multiple primary tumors require surgery other than pulmonary segmentectomy, wedge resection, patients unable to tolerate surgery(Figure 1).
Segmentectomy was categorized into simple or complex from the standpoint of technical aspect: resection of superior segment of the lower lobe or the lingular segment was defined as simple. Complex segmentectomy was resection of segment other than that to be resected in the simple segmentectomy, beside, complex segmentectomy was defined as resection of a segment that had more than one intersegmental plane(7). Two or more intersegmental planes would make segmentectomy more technically diffificult, the operation time would be longer with lower success rate of inter-segmental visualization, and higher rate of post-operative complications.
Quality control standard
All patients underwent contrast-enhanced computer tomography(CT), three-dimensional reconstruction was completed using EDDA-IQQA software or 3D-slicer(before November 2017). CT guided preoperative localization was performed(Figure 2), except lesion located in apical, lingular or superior segment. Oncological margin length should be larger than 2cm or maximal diameter of lesion.
Anaesthesia and incision
The anaesthesia procedures were the same in both groups. All patients received combined intravenous and inhalation anesthesia, with double-lumen endotracheal intubation. The patient was kept in lateral decubitus position, both cranial and caudal side was pushed down like a fold knife to make intercostal space wider, uni-portal VATS was applied. All patients were extubated after operation. Postoperative patient-controlled analgesia was provided.
A single incision, about 3 cm long, was performed at the fifth intercostal space along the anterior axillary line. Plastic wound protector was used. During operation, a 10-mm 30-degree thoracoscope (Pinpoint, Novadaq Technologies ULC, Stryker, for NIF-VATS segmentectomy; Karl Storz for ID-VATS segmentectomy) was placed at the superior side of the incision, several thoracoscopic instruments were simultaneously fitted into the uni-port beneath the thoracoscope.
Segmentectomy using inflation-deflation method or NIF imaging
Following ligation of the corresponding segmental artery, bronchus, and vein according to preoperative CT and three-dimensional reconstruction, intersegmental plane was identified by inflation-deflation method or near-infrared fluorescence imaging.
Using inflation-deflation method, the collapsed pulmonary tissue was initiated to fully re-expand with controlled airway pressure under 20cm H2O by pure oxygen, followed by single lung ventilation. After an interval of approximately 20 minutes, an irregularly curved demarcation was identified naturally between the deflated preserving segments and the inflated target segment.
We observed ICG fluorescence using a near-infrared thoracoscope. ICG was reconstituted into distilled water to produce a 2.5 mg/ml solution, and a volume of 6-10mL (dose of 15mg to 20mg) was injected in a peripheral intravenous catheter, followed by 10 ml of saline solution. The intersegmental plane of the targeted segment became clearly visible on infrared thoracoscopy about 15 seconds after injection, and could be marked using electrocautery.
A monopolar cautery hook was used to divide the pulmonary parenchyma of the intersegmental plane from the central side toward the peripheral side along the marked line, and anatomical segmentectomy was achieved using autosuture's cartridges.
When the ICG fluorescence was too dim to enable any visualization of the intersegmental border, or only part of the intersegmental border could be found in NIF-VATS group; the target segment was not demarcated from the rest of the lung in ID-VATS group, successfully resection along the border could not be achieved, it was regarded as “unclear intersegmental boarder”. Then intersegmental vein should be fully dissected, the target segment was excised along it.
Surgical margin, the distance between the cut end uncovered by visceral pleura and the tumor margin, was evaluated macroscopically to confirm that the surgical margin was not less than the maximum tumor diameter or 20 mm. If tumor free margin was not achieved, extended segmentectomy would be performed.
Lymph node sampling was performed when intra-operative pathology showed minimal invasive adenocarcinoma(MIA) or invasive adenocarcinoma(IAC).
To control air leakage after segmentectomy, partial closure of the visceral pleura, the use of fibrin glue, or reinforcement with a absorbable pad on the intersegmental plane were allowed.
Extubation criteria included: 1.hemodynamic stability; 2.stable spontaneous ventilation (respiratory rate < 30/min, increase in respiratory rate < 10/min); 3.normal arterial blood gas analysis with low-flow oxygen inhalation (PaO2 > 80mmHg, increase in PaCO2 <10mmHg, pH > 7.30, SpO2> 90%); 4.clear consciousness.
Chest Tube Remove
One 22F chest drain was inserted to thoracic cavity at the end of the operation, it was placed at posterior part of the uniportal incision. Drain removal criteria were as follows: no observed air leak and total drainage less than 200ml in 24 hours; normal chest roentgenograph; normal vital signs; good overall medical status. No patient was discharged with a chest tube in situ.
Postoperative Treatment and Follow-Up
Patients with ASA score >2, or age >70 years would go to ICU after operation. Mean stay in ICU was 2 days. Respiratory rehabilitation included: oxygen administration, in patients who have an elevated PaCO2 preoperatively, oxygen saturation is maintained at 90% or less, preserving the hypoxic drive to breathe; early physical exercise; pain control; prevention of cardiac arrhythmias, myocardial infarction, deep venous thrombosis and pulmonary thoromboembolism.
Chest radiography was performed at the first day postoperatively and every 3 days until discharge. Drinking and meal intake were resumed after bowel sounds returned with no nausea or vomiting in both groups.
Postoperative wound pain was monitored using the Visual Analogue Scales(VAS). The scale is an integer scale of 0–10, where 0 is no pain and 10 is the worst pain imaginable. VAS was evaluated on postoperative days 1, 3, 7, 14, 30, 60.
Statistical Analysis
SPSS 16.0 for Windows (IBM, Armonk, NY) was used for analysis. To minimize the impact of potential confounders and selection bias, propensity score analysis was used to compensate for the differences in baseline patient characteristics between the two groups of patients. Patients in the two groups were 1:1 matched using the nearest propensity score on the logit scale. Variables that could influence the outcomes of treatment were matched, including age, gender, body mass index (BMI), ASA status class, and maximal lesion size. After PSM, differences in continuous and categoric clinical characteristics were compared.
Continuous data are presented as mean and SD and were analyzed with two-sample Student’s t tests for independent data. Categorical variables are given as a count and percentage of patients and analyzed with the χ2 or Fisher’s exact test. All tests were two-sided, P-values <0.05 were considered statistically significant. SPSS Statistics 16.0 (IBM Corp, Armonk, NY) was used for statistical evaluations.