Keywords
localization - methylene blue - coil - lung nodule
Introduction
As low-dose computed tomography (CT) has increasingly been used for screening efforts,
the rates of lung nodule detection have risen.[1]
[2]
[3] To effectively determine whether the nodules are malignant or benign, wedge resection
via video-assisted thoracoscopic surgery (VATS) has been widely used owing to its
minimally invasive nature and the limited among or tissue resected during this procedure.[4]
[5]
[6] The use of preoperative CT-guided localization has been shown to significantly improve
lung nodule VATS-based wedge resection technical success rates.[7]
[8]
[9] However, at present, there has been insufficient research regarding the optimal
approaches to localization of these nodules prior to resection.[10]
[11]
In the present study, we compared the relative clinical efficacy of preoperative CT-guided
coil and methylene blue lung nodule localization strategies.
Materials and Methods
This was a retrospective analysis conducted at a single center. Our Institutional
Review Board approved this study, and the requirement for participant written consent
was waived owing to the retrospective nature of the study design.
Study Design
A total of 91 patients underwent CT-guided localization and VATS resection of lung
nodules at our center between January 2014 and December 2018 ([Table 1]). Prior to December 2014, 34 patients had undergone methylene blue–based localization,
whereas the remaining 57 patients treated after December 2014 underwent coil-based
localization ([Fig. 1]). Of these 91 patients, 19 had previously undergone respective surgery to remove
tumors (lung cancer: 11; colorectal cancer: 4; liver cancer: 1; renal cancer: 1; esophageal
cancer: 1; and breast cancer: 1). For each patient, discussions with thoracic surgeons,
oncologists, and radiologists were used to inform decisions regarding the resection
of lung nodules.
Fig. 1 The flowchart of this study.
Table 1
Comparison of data between coil and methylene blue groups
|
Coil group
|
Methylene blue group
|
p-Value
|
|
Patient-based analysis
|
|
Patients number
|
57
|
34
|
|
|
Age (y)
|
59.6 ± 9.8
|
60.1 ± 11.0
|
0.842
|
|
Gender (male/female)
|
25/32
|
13/21
|
0.599
|
|
Tumor history
|
15
|
5
|
0.196
|
|
Patients with multiple target nodules
|
12
|
7
|
0.851
|
|
Nodule-based analysis
|
|
Nodules number
|
71
|
42
|
|
|
Diameter (mm)
|
9.1 ± 5.2
|
9.7 ± 4.2
|
0.529
|
|
Natures of nodules
|
|
Solid
|
33
|
24
|
0.521
|
|
GGN
|
11
|
6
|
|
Mixed GGN
|
27
|
12
|
|
Nodule–pleura distance (mm)
|
5.6 ± 5.6
|
8.4 ± 7.1
|
0.033
|
|
Side (left/right)
|
25/46
|
18/24
|
0.419
|
|
Lobe (upper/nonupper)
|
30/41
|
20/22
|
0.579
|
|
Technical success of localization
|
67
|
41
|
0.416
|
|
Successful wedge resection
|
69
|
41
|
1.000
|
|
Duration of localization (min)
|
15.4 ± 5.2
|
14.3 ± 3.6
|
0.204
|
Abbreviation: GGN, ground glass nodule.
Study inclusion criteria included: (1) a maximal long-axis lesion diameter ≤ 30 mm;
(2) a nodule–pleura distance ≤ 30 mm; and (3) nodules lacking a definite pathological
diagnosis. Exclusion criteria included: (1) a lesion diameter < 3 mm; (b) a typical
benign lesion, such as a calcification or one that had reduced in size upon follow-up;
and (3) diffused multiple lung nodules.
CT-Guided Methylene Blue Localization
A 16-row CT (Philips, Cleveland, Ohio, United States) device was used for all procedures,
with respective tube voltage and current settings of 120 kV and 150 mA and a scanning
thickness of 2 mm.
Patients were positions so as to facilitate the shortest required pathway for needle
insertion, after which the lung parenchyma was punctured using a 22G needle (Cook,
Bloomington, Indiana, United States, [Fig. 2]) positioned such that the needle tip was within 1 cm of the lesion site. Next, patients
were steadily injected with ∼0.5 mL methylene blue while slowly removing the needle
such that the methylene blue remained above the visceral pleura. A follow-up CT scan
was then conducted to check for any procedure-associated complications.
Fig. 2 The lung nodule was located by methylene blue which was injected by a 22G needle.
CT-Guided Coil Localization
All CT parameters were identical to those for the methylene blue localization group.
Following needle insertion with an 18G needle (Precisa, Roma, Italy, [Fig. 3]), a 50-mm long coil that was 0.038 inches in diameter (Cook) was partially inserted
into the lung parenchyma. The needle was then gradually removed such that the tail
of the coil remained above the visceral pleura. A follow-up CT scan was then conducted
to check for any procedure-associated complications.
Fig. 3 The lung nodule was located by coil which was sent by an 18G needle. (A) The needle
was sent near the nodule (arrow). (B) The coil (arrow) was partially placed in the
lung tissue and the coil tail remained above the visceral pleura.
VATS Procedure
Owing to the risk of methylene blue diffusion, VATS in these patients was conducted
within 3 hours of localization wherever possible. Wedge resection was conducted based
on methylene blue visualization, and when such visualization was not possible, a lobectomy
was instead conducted.
For patients who had undergone coil localization, VATS was performed within 24 hours
of localization, with coil tail visualization being used to guide the wedge resection
procedure. When the tail of the coil was not visible, palpation was used in an attempt
to locate it. When this failed, a lobectomy was conducted.
The department of pathology conducted a rapid pathological examination of resected
wedge lung parenchymal tissue. When nodules were diagnosed as being more advanced
than mini-invasive adenocarcinoma, further lobectomy and lymph node dissection were
conducted.
Definitions
The technical success of either CT-guided localization approach was based on the successful
visualization of the methylene blue dye or the coil tail, as appropriate, when conducting
the VATS procedure. Wedge resection technical success was defined based up the identification
of the lesion of interest within the resected lung parenchymal tissue.
Statistical Analysis
Categorical variables were compared via Fisher's exact test or chi-square tests. Continuous
variables are means ± standard deviation, and were compared via Student's t-tests or Mann–Whitney's U tests. A p < 0.05 was the significance threshold. SPSS v16.0 (SPSS Inc., Illinois, United States)
was used for all statistical testing.
Results
Technical Success of CT-Guided Localization
A total of 42 lung nodules in 34 patients underwent methylene blue–based localization
([Table 1]), with a technical success rate of 97.6% (41/42). Methylene blue was not detectable
in the remaining patient owing to VATS having been conducted 24 hours postlocalization
as a result of an unexpected rise in blood pressure.
A total of 71 lung nodules in 57 patients underwent coil localization ([Table 1]), with a technical success rate of 94.4% (67/71). The coil tail was not visible
in the remaining four patients during VATS owing to the coil having been fully inserted
into the parenchyma of the lung.
Localization technical success rates were comparable between these two study groups
(p = 0.416).
Procedure-Related Pneumothorax
A total of three and seven patients in the methylene blue and coil groups, respectively,
suffered from procedure-associated pneumothorax (8.8 vs. 12.3%, p = 0.870). Only a single patient in the coil group needed to undergo chest tube drainage,
and this patient was still able to undergo VATS 24 hours following coil localization.
Technical Success of Wedge Resection
In the methylene blue and coil groups, the respective rates of wedge resection technical
success were 97.6% (41/42) and 97.2% (69/71) (p = 1.000, [Table 1]). Patients being assessed for multiple lung nodules underwent a single one-stage
VATS procedure. Negative margins were confirmed in all resected segments of lung parenchymal
tissue. While four patients in the coil localization group had suffered from technical
failure during the localization procedure, two of these patients were able to undergo
successful wedge resection because the tail of the coil was palpable during the VATS
procedure.
Patients in the coil group had a significantly longer period of time between localization
and VATS than those did in the methylene blue group (13.2 vs. 2.5 hours, p = 0.003). However, there were no significant differences in VATS duration, blood
loss, final diagnosis, or surgical types between these two localization groups ([Table 2]).
Table 2
Details of VATS and final diagnoses
|
Coil group
|
Methylene blue group
|
p-Value
|
|
Nodules number
|
71
|
42
|
|
|
Types of surgery
|
|
Wedge resection
|
49
|
32
|
0.713
|
|
Wedge resection + lobectomy
|
20
|
9
|
|
Lobectomy
|
2
|
1
|
|
Duration between localization and VATS (h)
|
13.2 ± 25.5
|
2.5 ± 3.9
|
0.003
|
|
Duration of VATS (min)
|
151.5 ± 76.3
|
139.1 ± 78.3
|
0.458
|
|
Blood loss (mL)
|
112.5 ± 112.4
|
103.2 ± 98.3
|
0.693
|
|
Final diagnoses
|
|
Invasive adenocarcinoma
|
26
|
13
|
0.975
|
|
MIS
|
2
|
1
|
|
AIS
|
4
|
4
|
|
Precancerous lesion
|
10
|
5
|
|
Squamous cells carcinoma
|
1
|
1
|
|
Metastasis
|
1
|
1
|
|
Benign
|
27
|
17
|
Abbreviations: AIS, adenocarcinoma in situ; MIS, microinvasive adenocarcinoma; VATS,
video-assisted thoracoscopic surgery.
Discussion
In this study, we compared the relative clinical efficacy of methylene blue and coil-based
approaches to preoperatively localize lung nodules. We found that the rates of technical
success for both localization (97.6 vs. 94.4, p = 0.416) and subsequent wedge resection (97.6 vs. 97.2, p = 1.000) were comparable for these two approaches.
Many previous reports have highlighted the relative advantages of the two localization
strategies utilized in the present study.[4]
[10] Methylene blue localization offers the advantages of being both affordable and simple
to implement,[9] but its potential for rapid diffusion requires that VATS be conducted as quickly
after localization as possible. Indeed, in the present study, a single patient suffered
from technical failure of the methylene blue–based localization approach owing to
the delay which they experienced in undergoing VATS. While this only affected one
patient in the present report, it underscores the importance of conducting VATS as
quickly as possible. Consistent with this, we found that among assessed cases, there
was a significantly longer period of time between localization and VATS for patients
in the coil group relative to those in the methylene blue group (p = 0.003). This is consistent with the fact that coil localization can increase the
window during which VATS can be conducted. However, coil localization is more complex
to perform, necessitating increased operator skill levels.
Coil localization also offers an additional advantage over methylene blue localization,
in that in some cases the coil may be inadvertently inserted fully into the parenchyma
of the lung. In these cases, it may still be possible to conduct wedge resection provided
the coil tail can be palpated during VATS.[4] Indeed, in the present study, two of the four patients (50%) who experienced coil
localization technical failure were still successfully treated via VATS wedge resection
owing to successful coil palpation.
We observed similar pneumothorax rates between the two study groups (8.8 vs. 12.3%,
p = 0.870), suggesting these two localization strategies may have similar safety profiles.
A previous study found the similar and high pneumothorax rates (46 vs. 50%) after
core (19G) and fine (22G) needle biopsy for lung nodules.[12] Another study found the repeat punctures was the risk factor of the higher pneumothorax
rate.[13] Compared with CT-guided lung biopsy, CT-guided methylene blue or coil localization
usually did not require repeat lung puncture. These findings may explain the reason
why both needles (22G and 18G) caused the low and similar pneumothorax rate in this
present study. In addition, only a single patient in this study necessitates the insertion
of a chest tube, suggesting pneumothorax does not have a significant impact on subsequent
VATS performance.
Hookwire localization has been widely used to localize lung nodules in many previous
reports,[11]
[14] and while this procedure is simple to conduct, it suffers from substantially higher
rates of complications.[14] Previous studies[11]
[14] comparing hookwire and coil localization complication rates found that the coil-based
approach was associated with markedly reduced rates of patient pain and complications.
Other researchers have employed the use of a radiolabel-based localization strategy,
as this approach is also simple to implement and has a low risk of complications.[15] This approach, however, necessitates the use of intraoperative X-ray guidance and
exposes patients to significantly higher levels of radiation.
There are certain limitations to this study. First, this was a retrospective report
and is thus susceptible to selective bias. Second, as the sample size was limited
for this study, it is difficult to draw definitive conclusions regarding our findings.
Third, this was a single-center study. As such, it is important that larger multicenter
prospective studies be conducted in the future.
In summary, we found that both methylene blue and coil-based localization can be safely
and effectively used to achieve high rates of successful lung nodule wedge resection
for diagnostic purposes. Relative to methylene blue injection, the coil-based approach
is compatible with a longer delay between the localization and VATS procedures.
