|Year : 2020 | Volume
| Issue : 5 | Page : 967-973
Expert consensus workshop report: Guidelines for preoperative assisted localization of small pulmonary nodules
Baodong Liu1, Chundong Gu2
1 Thoracic Surgery Department, Xuanwu Hospital, Capital Medical University, Xicheng, Beijing, China
2 Thoracic Surgery Department, First Hospital Affiliated Dalian Medical University, Dalian, China
|Date of Submission||02-Apr-2020|
|Date of Decision||13-Jul-2020|
|Date of Acceptance||20-Aug-2020|
|Date of Web Publication||29-Sep-2020|
Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing 100053
Source of Support: None, Conflict of Interest: None
Along with increasing incidence of operable small pulmonary nodules, it becomes difficult to localize nodules via palpation. Accurate localization of small pulmonary nodules has remained a big challenge in lung surgery. Therefore, several techniques for preoperative localizing small pulmonary nodules have evolved, but the advantages and disadvantages of each method remain unclear. We reviewed computed tomography-guided percutaneous and bronchoscopic preoperative assisted localization for small pulmonary nodules. Original, peer-reviewed, and full-length articles in English and Chinese were searched with PubMed and Wanfang data. Case reports and case series with <20 patients were excluded. All localization techniques showed good reliability, but some carry a high rate of major or minor complications and drawbacks. No ideal localization technique is available; thus, the choice of preoperative assisted localization technique still depends on surgeons' preference and local availability of both specialists and instruments.
Keywords: Assisted localization, guidelines, pulmonary nodules
|How to cite this article:|
Liu B, Gu C. Expert consensus workshop report: Guidelines for preoperative assisted localization of small pulmonary nodules. J Can Res Ther 2020;16:967-73
| > Introduction|| |
Low-dose computed tomography (LDCT) screening has increased the detection rate for small pulmonary nodules with ground-glass opacity (GGO) in the peripheral lung parenchyma. Due to certain probability of malignancy, clinicians have focused on the diagnosis and treatment of small pulmonary nodules. It is difficult to make the definitive diagnosis of small pulmonary nodules using conventional examination means such as biopsy, bronchoscopy, and positron emission tomography-CT. However, video-assisted thoracoscopic surgery (VATS) has become an important method for the diagnosis and treatment of small pulmonary nodules., Suzuki et al. found that in their series of cases in which thoracoscopy was converted to thoracotomy, 46% were due to the inability to localize nodules. This percentage increases to 63% if the nodule is <10 mm or >5 mm from the pleural surface. Therefore, how to accurately locate small pulmonary nodules as quickly as possible during operation, precisely remove tumor to the greatest extent, and provide maximum protection for pulmonary function become a significant issue faced by thoracic surgeons. For this purpose, China Minimally Invasive Diagnosis and Treatment in Lung Cancer Group organizes related experts to compile Expert Consensus Workshop Report: Guidelines for Preoperative Assisted Localization of Small Pulmonary Nodules on the basis of clinical experiences and evidence-based medicine and through repeated discussions and argumentations. The consensus is formally published to provide guidance for preoperative assisted localization of small pulmonary nodules.
Level of evidence and grading of recommendations of the consensus are:
- Grade 1A: The recommendation is based on high-level evidences (rigorous meta-analysis or randomized controlled trial [RCT] result), and the panel reaches a consensus
- Grade 1B: The recommendation is based on high-level evidences (rigorous meta-analysis or RCT result), and the panel has a little controversy
- Grade 2A: The recommendation is based on low-level evidences, and the panel reaches a consensus
- Grade 2B: The recommendation is based on low-level evidences, and the panel does not reach a consensus, but there is not much controversy
- Grade 3: The panel has much controversy.
| > Significance of Recommendation on Preoperative Assisted Localization of Small Pulmonary Nodules|| |
Results of the US National Lung Screening Trial and Dutch–Belgian Randomized Lung Cancer Screening Trial (NELSON) demonstrate that LDCT lung cancer screen can decrease mortality of lung cancer patients. Consequently, the number of patients diagnosed as small pulmonary nodules is ever increasing. However, these nodules can hardly be seen on the surface of the lung, so the success rate of lesion localization via intraoperative finger palpation or instrument sliding is only 30%., For some patients, inaccurate localization may lead to conversion to an open thoracotomy or even operational failure. Therefore, preoperative assisted localization of small pulmonary nodules is particularly important.
Several studies have documented specific indications in which localization techniques should be employed. Suzuki et al. recommend that localization techniques be used when the nodules are <10 mm in size or more than 5 mm from the visceral pleural surface or both. Ciriaco et al. conclude that preoperative hookwire marking appears to be a safe procedure, it may be beneficial when the pulmonary nodules size is <10 mm and/or the distance from the visceral pleural surface is >15 mm, and advisable when pulmonary nodules size is >10 mm and/or the distance from the visceral pleural surface is between 15 and 25 mm. Nakashima  developed three criteria: (1) nodule diameter of 5 mm or less, (2) ratio of maximum diameter of nodule to minimum distance between visceral pleural surface and inferior border of nodule is ≤0.5, and (3) nodule is of low density on CT. The authors recommended that localization techniques be used if two or more of these criteria are met.
Indications for preoperative assisted localization include: (1) solitary or multiple small (i.e., diameter <15 mm) or deep (i.e., >10 mm from visceral pleura) pulmonary nodules, (2) finding of imaging as pure ground-glass nodule or subsolid nodule, and (3) difficult to localize nodules via palpation intraoperative (Grade 1B).
| > Techniques for Preoperative Assisted Localization of Small Pulmonary Nodules|| |
Currently, many preoperative assisted localization techniques can effectively enhance the safety of operation and the success rate of nodule resection.
Existing techniques for preoperative assisted localization of small pulmonary nodules mainly include: (1) CT-guided percutaneous assisted localization, (2) bronchoscopic assisted localization, and (3) CT virtual three-dimensional (3D) assisted localization (Grade 2A).
CT-guided percutaneous assisted localization technique
Percutaneous hookwire localization
Hookwire localization is the most frequently used technique at present.,,, Hookwire is a kind of localization needle. In general, a 21-gauge needle is used for localization of small pulmonary nodules. Hookwire is composed of two parts: A hook (1 cm in length after deployment) at the tip and a 30 cm metal wire connected with it. First, position of small pulmonary nodules is confirmed via high-resolution CT. Then, puncture site is chosen. After routine disinfection, draping, and local anesthesia with 2% lidocaine, hookwire trocar is inserted into pulmonary tissue through the skin. CT scanning is repeated to confirm that hookwire is at the target area. Then, hookwire is pushed forward for 3–5 mm, with the bevel of trocar facing toward the target area; the metal wire is released, the trocar is withdrawn, and front-end metal hook is deployed and fixed around the target area. Be cautious to avoid direct puncturing of nodule. The recommended distance between the hookwire and the nodule is <1 cm. At this target area, a sense of resistance can be felt if the metal wire is pulled gently. CT scanning is performed again to evaluate the existence of bleeding, pneumothorax, or other complications. After good anchoring and fixing by metal hook is confirmed, the metal wire is bent and closely attached to the skin and covered with gauze. Then, VATS shall be performed within 1–2 h. Frequent metal wire displacement and even detachment is still the main cause for hookwire localization failure.
Percutaneous coil loalization
procedure method is substantially the same with hookwire localization. Puncture site is determined via CT scanning, and the distance between the target area and the nodule shall be <1 cm., Then, CT scanning is repeated to confirm the target area is correct, and the coil is released into the lung. Without inverse hook, reliable fixation is guaranteed by the friction between coil and pulmonary tissue. There are two coil localization methods that are most frequently used: One is that the coil will be positioned inside the lung and the other is that the tail of the coil will be positioned outside visceral pleura. These two methods are not significantly different between each other in terms of success rate and complication incidence. Finally, CT scanning is necessary to confirm the target area and evaluate the existence of bleeding, pneumothorax, or other complications.
Localization via percutaneous liquid material injection
under guidance of CT, liquid material is injected after percutaneous puncture such as lipiodol, medical glue, methylene blue, and indocyanine green. The recommended distance between injection site and nodule is <1 cm. The stylet is extracted, and the syringe is withdrawn without blood and air. After entering of needle into vessel or bronchus is excluded, liquid material is injected. Lipiodol is easily available and featured by small diffusion range and long duration after injection locating. As a fat-soluble radiopaque contrast agent, lipiodol is unlikely to have immune reaction with nodule. Of high density, lipiodol turns into a mass after it is injected into pulmonary tissue, and thus, the position of nodules can be sensed accurately during operation. Furthermore, lipiodol has stable property, so it is not needed to perform operation immediately after localization. Operation can be performed within 1–2 days. Medical glue has good biological safety and small diffusion range after injection and turns into a mass after it is injected into pulmonary tissue, and thus, the position of nodules can be sensed accurately during operation. However, it has certain irritating odor, which may enter the trachea along with patient's respiration and cause irritable cough in case of too rapid injection. In addition, puncture site results in mild chest pain. Methylene blue is a low-price option and easily available. The procedure just brings mild pain. However, methylene blue is difficult-to-identify on pulmonary surface with pigmentation, and its diffusion is fast. Therefore, operation should be performed within 1–2 h after localization. Moreover, methylene blue overdose has a disadvantage of influencing localization. Clinical practices have proved that combined use of hookwire and methylene blue in localization is safe and effective, which not only overcomes shortcomings of methylene blue including fast diffusion and difficult identification but also avoids localization failure caused by hookwire detachment. Localization with mixture of lipiodol and methylene blue has also been used clinically. In recent years, marking off with indocyanine green under near-infrared light has been introduced. Compared with former colorant, indocyanine green achieves durable staining and avoids localization failure caused by displacement. As a water-soluble substance, indocyanine green is metabolized quickly in vivo. Furthermore, its safety has been verified. When used in combination with preoperative 3D assisted printing and localization technology, it can effectively reduce unnecessary radiation exposure that occurs during conventional localization process.
Bronchoscopic assisted localization technique
Localization under electromagnetic navigation bronchoscopy
Electromagnetic navigation bronchoscopy (ENB), on the basis of thin-section CT reconstructed images, utilizes extracorporeal electromagnetic positioning plate to guide a probe with microsensor inside bronchus to locate nodule. In this way, ENB system breaks through the small size of ultrathin bronchoscopes (outer diameter: 2.8–3.5 mm) and allows better maneuverability, and they can visualize deeper into the tracheobronchial tree to reach the position around nodule, performs localization through puncture, and injects dye, hardener, indocyanine green, etc., to mark the position of nodule. ENB has a unique advantage in localization of peripheral pulmonary nodules (can reach up to the seven-generation bronchi), especially pulmonary nodules of about 1 cm.,,,
Virtual bronchoscopic navigation localization technology
Virtual bronchoscopic navigation (VBN) localization technology, also known as virtual assisted lung mapping (VAL-MAP), is first proposed and applied by Japanese Masaaki Sato in 2014. It utilizes bronchoscope to inject fluorescent dye around small nodules and then conducts simultaneous marking through computer-based 3D mapping, i.e., lung mapping. Besides application in nodule localization, this technology can use the geometrical information of pulmonary surface obtained from lung mapping to provide navigation for thoracoscopic sublobectomy and selection of safe and adequate surgical margin. Within 24 h before operation, bronchoscope is guided to reach the position around nodule under laryngopharynx topical anesthesia or general anesthesia. Then, radiopaque indigocarmine developed under X-ray is injected, and lung mapping is done via CT scanning reconstruction to identify the range of surgical resection.
Till now, VAL-MAP has just been subject to small-range verification and application overseas and rarely reported domestically. According to foreign reports, VAL-MAP has been verified in more than 100 cases of wedge resection of <1 cm (diameter) solitary and multiple pulmonary nodules, conventional segmentectomy  (localization via pulmonary artery), nonconventional segmentectomy (subsegmentectomy, segmentectomy localized via pulmonary artery, extended segmentectomy, etc.), lobectomy, and bilateral segmentectomy  and shows good safety and operability.,
Those VBN systems that are currently available, including LungPoint ® system and Directpath ® system, can establish bronchoscopic transparenchymal nodule access for nodules that have no guide channel.
Computed tomography virtual three-dimensional assisted localization technique
Three-dimensional printing assisted localization technique
researchers have tried to use computer software in the lung and positioning template reconstruction and then utilize 3D printing technology to print positioning template for performing percutaneous puncture and localization of pulmonary small nodule. Furthermore, the safety and effectiveness of this technique have been preliminarily verified in a clinical study.
Virtual reality assisted localization technique
through computer software, reconstruct patient's CT images into 3D images quickly and accurately. Through wearable virtual reality equipment, it intuitively presents relative position of artery, vein, trachea, bronchus, lung tissue, and nodule to operator, precisely measures lumen diameter and distance, shows the anatomical boundary of pulmonary segment, and assists in delineation of surgical margin.
Gill et al. have reported their combined use of C-arm CT and 3D software reconstruction in intraoperative real-time guiding of T-bar for localization (image-guided VATS). Phase II clinical trial has been conducted.
Preoperative assisted localization technique requirements: (1) the operation requires complete removal of the puncture passage and the material of localization and (2) the operation ensures that the surgical margin is negative while preserving as much normal lung tissue as possible. Therefore, the puncture passage should have the shortest distance from the nodule to the visceral pleura (Grade 2A).
| > Current Technical Advantages and Disadvantages|| |
Risks and technical bottleneck of percutaneous assisted localization
Percutaneous assisted localization
Percutaneous assisted localization has a certain risk of complications. CT-guided percutaneous assisted localization becomes the most frequently used preoperative localization means in clinical practice owing to its advantages including easy manipulation, short operation time, high success rate, and low cost. The most frequently applied localization technique is hookwire localization , because it has low complication incidence, guarantees the safety and effectiveness of VATS, and significantly decreases occurrence rate of conversion to an open thoracotomy during VATS. Due to certain risks and complications of percutaneous assisted localization, VATS should be performed as soon as possible after localization. Hookwire localization performed in hybrid operation room can shorten the time period from localization to VATS and effectively reduce the incidence of related complications. However, such application is limited by small quantity of hybrid operation rooms and limitation of resources., The safety and effect of coil localization have been proved in research. In spite of reports on intraoperative conversion to a thoracotomy or even operational failure caused by complication such as coil displacement in the lung, the incidence of its complication is still significantly lower than hookwire-assisted localization technique. Some scholars even believe that the complication incidence of coil localization is the lowest., If operation is terminated due to various reasons, hookwire will be difficult to handle. Compared with these two methods, localization assisted by percutaneous lipiodol injection avoids the risk of metal object placement. In addition, the latest meta-analysis shows that its success rate is the highest among all assisted localization techniques., However, need of wearing lead apron during operation due to radiation exposure is a disadvantage of this technique.
Complications of percutaneous assisted localization
(1) Pneumothorax: The most common complication refers to pneumothorax that resulted from piercing of visceral pleura by puncture needle. The incidence of pneumothorax is up to 35%, but most patients have no obvious discomfort, and a few severe emphysema patients need thoracic closed drainage. (2) Intrathoracic hemorrhage: Common cause is rupture of intercostal or intrapulmonary vessels, and the incidence is about 15%. In case of hemothorax, bleeding can be stopped during VATS, and no preoperative treatment is required. (3) Displacement of localization point: This is a severe complication of localization and may directly cause localization failure. The incidence of hookwire detachment is the highest, approximately 6%, and 3% and 1% for coil and lipiodol, respectively., (4) Others: Air embolism has been reported in some cases of hookwire localization, with incidence about 0.07%–0.15%. Its cause may be associated with cough or deep respiration of patient or positive pressure ventilation of anesthesia respirator. Besides, there is a case report of coil retaining in pulmonary tissue, probably because localization point is deep, coil is not taken out before wedge resection, and thus, the coil is not covered by resection range and left in pulmonary tissue.
Bottleneck of percutaneous assisted localization
(1) When the distance between tumor and visceral pleura is large, i.e., >4 cm, the incidence of puncture-related complication increases remarkably, and lobectomy is usually the optimal choice. (2) When the tumor is close to the heart and great vessel, puncture is technically feasible but may lead to lethal massive hemorrhage. In such case, puncture localization is not recommended. (3) For a few patients, the establishment of puncture passage may fail because of blockage by scapula, rib, and etc.
Blind area of preoperative assisted localization: (1) area <3 cm from mediastinum pleura (covering of sternum/costal cartilage), (2) regions <3 cm from interlobar fissures (cross-leaf localization), and (3) the area covered by bony structures such as the scapula. Due to the limitation of anatomical structure, the puncture passage may be longer, which will cause unnecessary large-area loss of normal lung tissue during resection, thus affecting the lung function to some extent (Grade 1B).
Advantages and disadvantages of bronchoscopic assisted localization technique
Advantages of bronchoscopic assisted localization
it is studied that compared with conventional percutaneous assisted localization, this technique can effectively reduce complications such as pneumothorax and bleeding and can locate some positions that are difficult to puncture anatomically (e.g., apical and diaphragmatic localization of pulmonary nodules). ENB is an invasive means, and there is rarely a large-scale case report of complication such as pneumothorax and bleeding till now.,,,, It can be affirmed that bronchoscopic assisted localization has fewer complications and higher safety than percutaneous assisted localization.
Disadvantages of bronchoscopic assisted localization technique
despite fewer complications, ENB-based localization methods have certain limitations, which impede clinical popularization and should be improved in future development. Take ENB assisted localization as an example. First, the accuracy of localization technique is restricted by the bronchoscope equipment. A thinner catheter helps to guide the bronchoscope into the thinner peripheral bronchi but significantly increases the difficulty of procedure. Second, the procedure for localization technique is complicated and requires a laryngopharynx topical anesthesia or general anesthesia operated by more experienced physicians, and the operation time is longer than most traditional localization methods. Third, the high cost of localization technique is not conducive to clinical promotion. In addition, ENB-assisted localization is limited by complicated multidisciplinary cooperation, preoperative path planning, and intraoperative navigational manipulation and thus still in the stage of clinical exploration.
Shortcomings of bronchoscopic assisted localization technique: (1) limited localization accuracy, (2) complicated localization procedure, and (3) higher localization costs (Grade 1B).
To sum up, each technique of preoperative assisted localization has certain advantages and disadvantages. Surgeons should choose suitable localization technique according to the conditions of their hospital. Preoperative 3D technology  and intraoperative anatomical localization  shall be used to double positioning of GGO lesions, which helps us to develop the best operation plan before surgery to avoid excessive removal of normal lung tissue.
Expert panel (listed in no particular order):
Baodong Liu (Xuanwu Hospital, Capital Medical University, Beijing 100053), Chundong Gu (The First Affiliated Hospital of Dalian Medical University, Dalian 116011), Chang Chen (Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433), Feng Yao (Shanghai Chest Hospital Affiliated to Tongji University, Shanghai 200030), Qun Wang (Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032), Jian Hu (The First Affiliated Hospital of Zhejiang Medical University, Hangzhou 310003), Liang Chen (The First Affiliated Hospital with Nanjing Medical University of Jiangsu Province Hospital, Nanjing 210036), Jie Jiang (The First Affiliated Hospital of Xiamen University, Xiamen 361001), Xiaofei Li (Tangdu Hospital, the Second Affiliated Hospital of Air Force Military Medical University, Xi'an 710038i), Lanjun Zhang (Sun Yat-sen University Cancer Center, Guangzhou 510060), Yue Yang (Beijing Cancer Hospital, Beijing 100142), Juwei Mou (Shenzhen Hospital of Chinese Academy of Medical Sciences, Shenzhen 518116), Guowei Che (West China Hospital of Sichuan University, Chengdu 610041), Wenzhao Zhong (Guangdong Provincial People's Hospital, Guangzhou 510080), Fan Yang (Peking University People's Hospital, Beijing 100044), Shun Xu (The First Affiliated Hospital of China Medical University, Shenyang 110001), Hongxu Liu (Liaoning Cancer Hospital and Institute, Shenyang 110042), Junfeng Liu (Fourth Hospital of Hebei Medical University Hospital, Shijiazhuang 050011), Changfa Qu (The Tumor Hospital of Harbin Medical University, Harbin 150000), Jianguo Chu (The First Affiliated Hospital of Dalian Medical University, Dalian 116011), Jianyong Ding (Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032), Xiuyi Zhi (Xuanwu Hospital Capital Medical University, Beijing 100053), Gening Jiang (Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433), Shugeng Gao (Cancer Hospital of Chinese Academy of Medical Sciences, Beijing 100021), Lunxu Liu (West China Hospital of Sichuan University, Chengdu 610041), and Haiquan Chen (Fudan University Shanghai Cancer Hospital, Shanghai 200032).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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