Fluoroscopy-guided fine-needle aspiration of deep-seated pulmonary masses in dogs and cats appears safe and accurate

Frédéric Jacob Atlantic Veterinary Internal Medicine & Oncology, Columbia, MD

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 PhD, DACVIM

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Abstract

OBJECTIVE

Deep-seated pulmonary lesions can be difficult to sample safely. The objective of this study was to determine the relative safety and accuracy of fluoroscopy-guided fine-needle aspiration of deep-seated pulmonary lesions regardless of their size and depth.

ANIMALS

Client-owned animals; 5 dogs and 5 cats.

CLINICAL PRESENTATION

Pulmonary lesion locations were determined on dorsoventral and lateral views using fluoroscopy. The lateral thoracic wall was aseptically scrubbed, and an indelible marker was used to mark the point of entry of the needle for sampling. The path of a 22-gauge needle attached to a syringe was followed using fluoroscopic guidance. Mass volume (Vma) and distance from skin and pleura to lesion (DSK-L and DPL-L) were recorded.

RESULTS

In dogs, mean Vma was 137.2 cm3 (range, 6.3 to 426.2 cm3). Mean DSK-L was 71 mm (range, 37 to 101 mm) and DPL-L was 33 mm (range, 16 to 71 mm). Exfoliative cytology results were consistent with carcinoma in 4 dogs and lymphoma in 1 dog. A minor postprocedural complication was noted in 1 dog. In cats, the mean Vma was 2.4 cm3 (range, 1.6 to 3.7 cm3). Mean DSK-L was 42 mm (range, 20 to 75 mm) and DPL-L was 21 mm (range, 12 to 32 mm). Cytology results were consistent with pulmonary carcinoma in 2 cats, inflammation in 2 cats, and necrotic debris in 1 cat.

CLINICAL RELEVANCE

Fluoroscopy-guided fine-needle aspiration of pulmonary masses is a safe and accurate technique to obtain cytologic samples irrespective of the size and depth of the lesions.

Abstract

OBJECTIVE

Deep-seated pulmonary lesions can be difficult to sample safely. The objective of this study was to determine the relative safety and accuracy of fluoroscopy-guided fine-needle aspiration of deep-seated pulmonary lesions regardless of their size and depth.

ANIMALS

Client-owned animals; 5 dogs and 5 cats.

CLINICAL PRESENTATION

Pulmonary lesion locations were determined on dorsoventral and lateral views using fluoroscopy. The lateral thoracic wall was aseptically scrubbed, and an indelible marker was used to mark the point of entry of the needle for sampling. The path of a 22-gauge needle attached to a syringe was followed using fluoroscopic guidance. Mass volume (Vma) and distance from skin and pleura to lesion (DSK-L and DPL-L) were recorded.

RESULTS

In dogs, mean Vma was 137.2 cm3 (range, 6.3 to 426.2 cm3). Mean DSK-L was 71 mm (range, 37 to 101 mm) and DPL-L was 33 mm (range, 16 to 71 mm). Exfoliative cytology results were consistent with carcinoma in 4 dogs and lymphoma in 1 dog. A minor postprocedural complication was noted in 1 dog. In cats, the mean Vma was 2.4 cm3 (range, 1.6 to 3.7 cm3). Mean DSK-L was 42 mm (range, 20 to 75 mm) and DPL-L was 21 mm (range, 12 to 32 mm). Cytology results were consistent with pulmonary carcinoma in 2 cats, inflammation in 2 cats, and necrotic debris in 1 cat.

CLINICAL RELEVANCE

Fluoroscopy-guided fine-needle aspiration of pulmonary masses is a safe and accurate technique to obtain cytologic samples irrespective of the size and depth of the lesions.

Introduction

Solitary pulmonary lesions are occasionally seen in dogs and cats. The main indication for sampling these lesions is to determine whether these nodules are benign or malignant. Establishing the nature of a thoracic lesion is paramount to making appropriate therapeutic decisions prior to considering more invasive and expensive options such as thoracotomy and lung lobectomy.

Transthoracic ultrasound guidance, tracheobronchoscopy, and CT guidance are some of the most common techniques used to sample pulmonary lesions in veterinary medicine. Transthoracic ultrasound-guided fine-needle aspiration (FNA) has the advantage of being readily available, minimally invasive, and associated with a low rate of complications.1 This technique also offers real-time visualization of the path of the needle into the diseased pulmonary parenchyma, improving the probability of obtaining a cytologic diagnosis. However, sampling is often limited to pulmonary lesions adjacent to the chest wall due to possible interference from aerated lungs.24

Obtaining samples from a solitary pulmonary lesion with tracheobronchoscopy is often complicated by 2 major factors. First, access to the soft tissue density is often limited to those lesions that are intraluminal in nature, and second, soft tissue densities located at the periphery of the pulmonary tissue cannot easily be sampled due to the relatively small size caliber of the airways in dogs and cats. Retrospective studies revealed that endoscopy-guided bronchoalveolar lavage is specific but insensitive for diagnosis of focal pulmonary lesions such as pulmonary neoplasia in cats5,6 and dogs.7

CT is commonly used in veterinary medicine to evaluate pulmonary lesions, the presence of intrathoracic metastases, and regional lymphadenopathy.8,9 Techniques for CT-guided FNA and biopsies of pulmonary masses in veterinary medicine have been described.10 Since CT-guided sampling does not provide real-time visualization of the path of the needle within the lungs, sampling becomes technically challenging and time-consuming and can lead to increased radiation exposure to the patient and staff. CT scan is often not suitable for sampling of deep-seated structures due to an increased risk of complications such as iatrogenic pneumothorax and/or hemorrhage.11,12

Transthoracic fluoroscopy-guided FNA (FGFNA) has been used in human medicine for several years as an alternative or complementary method to access deep-seated pulmonary pathologies.13,14 Fluoroscopy offers real-time visualization of the needle trajectory through the pulmonary tissue, which can improve sampling accuracy and decrease sampling time. It also provides the benefit of assessing for acute postprocedural complications such as the development of pneumothorax, pulmonary hemorrhage, or hemothorax. To the author’s knowledge, there has only been 1 study4 assessing transthoracic FGFNA in veterinary medicine. A study by McMillan et al4 evaluated the diagnostic and safety of FGFNA biopsy in dogs and cats with various pulmonary disease using a 20-gauge needle. Postprocedural complications close to 20% were reported in this study.

We hypothesized that transthoracic FGFNA using a 22-gauge needle would be a safe and accurate method to aid in the diagnosis of deep-seated pulmonary masses in dogs and cats. The goals of this retrospective study were to (1) describe an updated technique for sampling deep-seated pulmonary lesions, (2) evaluate the relative safety in obtaining a cytologic sample of pulmonary lesions regardless of their size and depth, and (3) assess the accuracy of obtaining a cytologic sample in dogs and cats.

Methods

Medical records of all client-owned cats and dogs that had undergone FGFNA of pulmonary masses at our hospital (private clinic setting) between January 1, 2011, and December 31, 2022, were reviewed. Signalment, presenting clinical signs, and laboratory (CBC, serum biochemistry, urinalysis, and prothrombin time/partial thromboplastin time) and imaging results (thoracic radiographs, abdominal and thoracic ultrasounds, and CT scans) were obtained when available. Included patients were those in which transthoracic ultrasound could not visualize the primary pulmonary lesion due to ultrasound-air interface. Cytologic results and recorded intra- and postprocedural complications were documented.

Case selection criteria

Orthogonal thoracic radiographs (left and right lateral and ventrodorsal views) were available for review. The location and size of the pulmonary lesion were obtained. On the ventrodorsal views, the shortest distance from the skin to the periphery of the lesion (DSK-L) were recorded. The documented distance was critical in determining the length of the needle needed for sampling. The distance between parietal pleura and the periphery of the lesion (DPL-L) was also obtained in each case. DPL-L measured the length of pulmonary tissue traversed before reaching the pulmonary mass.

Since the thoracic masses were not completely spherical, the volume of the mass was estimated using the formula used to calculate the volume of an ellipsoid (4/3 Π [radii of height X length X width]). The height and length of the masses were measured on lateral views, and the width was obtained on ventrodorsal views. The radius of each measurement was obtained by dividing each axis by 2. The volume of the mass was expressed in milliliters (1 mL = 1 cm3).

Prior to anesthesia, transabdominal and transthoracic ultrasonography was performed in all cases. For patients in which the thoracic lesions could not be visualized on ultrasound, transthoracic FGFNA was recommended as the next diagnostic step.

Procedure

All procedures were performed by the same clinician (FJ). Owners consented to the procedure after signing a financial estimate form. All dogs and cats were sedated with hydromorphone and midazolam, induced with propofol, intubated, and maintained on isoflurane. When under anesthesia, the patients were placed in sternal recumbency. Fluoroscopic images of the masses were obtained in dorsoventral and then lateral views to assess whether the lesions could be visualized on fluoroscopy to confirm their locations.

The thorax on the ipsilateral aspect of the mass was shaved and aseptically scrubbed. The fluoroscopy unit was placed perpendicularly (ie, lateral view) to the patient, and the point of entry of the needle was marked using an indelible marker under fluoroscopy guidance. The mark corresponded to the center of the pulmonary mass. The fluoroscopy unit was then repositioned in a dorsoventral view. Manual ventilation was stopped during the sampling, but the patient was allowed to breathe normally.

Attached to 6-mL syringes, 22-gauge needles of variable lengths were used for sampling. The length (25 to 127 mm) of the needle was chosen on the basis of the skin to mass distance, measured on previously obtained thoracic radiographs.

The needle (Figure 1) was inserted perpendicularly to the chest wall, and the path of the needle was monitored under fluoroscopy until it reached and then penetrated the soft tissue density. The plunger of the syringe was withdrawn several times until material was observed at the hub of the needle. The procedure was repeated 2 to 3 more times to sample different locations, since many neoplasms have an inflammatory component in the periphery or necrotic centers.1 Samples were sent for cytologic interpretation to an external laboratory.

Figure 1
Figure 1

Using fluoroscopy, the path of the needle (star) is followed until it reaches the solitary pulmonary lesion (arrow).

Citation: Journal of the American Veterinary Medical Association 262, 1; 10.2460/javma.23.07.0413

Immediately after the procedures, fluoroscopic images of the thoracic cavity were obtained to assess for acute hemorrhage and/or pneumothorax. All patients were recovered in the ICU. Breathing patterns and pulse oximetry were monitored during the recovery period.

Complications were recorded. Minor complications were described as the presence of pneumothorax, pulmonary hemorrhage, or hemothorax not requiring medical interventions. Major complications included the aforementioned complications but with the need for medical interventions such as placement of a chest tube, blood transfusion due to hemorrhage, or prolonged ICU stay with oxygen supplementation.

Statistical methods

Retrospective and descriptive case series. Descriptive statistics were recorded for mass volume and DSK-L as well as DPL-L. Procedural complications were documented and characterized as minor or major.

Results

Between January 1, 2011, and December 31, 2022, 5 dogs and 5 cats underwent transthoracic FGFNA of deep-seated pulmonary lesions.

Dog data

Mixed breed (n = 1), Labrador Retriever (1), Norwegian Elkhound (1), Boxer (1), and American Bulldog (1) were included in this study. Three dogs were male castrated (3/5 [60%]) and 2 were spayed female (2/5 [40%]). Average age was 11.6 years old (range, 10 to 14 years old). The mean weight was 25.4 kg (range, 10.3 to 37.4 kg).

Presenting clinical signs included coughing in 80% of the cases, excessive panting (20%), and weight loss (20%). In 1 dog with oral melanoma (dog 3), no respiratory signs were noted but a pulmonary nodule was noticed after thoracic radiographs were obtained for staging purposes (Table 1).

Table 1

Description of presenting clinical signs, pulmonary mass volume, sampling distances, complications, and cytologic diagnosis in 5 dogs with solitary pulmonary lesions.

Dog 1 Dog 2 Dog 3 Dog 4 Dog 5
Presenting signs Coughing Coughing Asymptomatic Coughing Coughing
Weight loss Oral melanoma Panting
Oral plasmacytoma
Vma (mL) 6.3 134.8 27.6 86.5 426.2
DSK-L (mm) 37 75 94 101 50
DPL-L (mm) 16 15 45 71 20
Complications < 24 h/> 24 h No/No No/No No/No No/No No/Minor
Exfoliative cytology Susp carcinoma with macrophagic inflammation Susp carcinoma with neutrophilic inflammation Susp carcinoma with mixed inflammation Probable lymphoma Susp carcinoma with neutrophilic inflammation
Sample quality High cellularity and good quality High cellularity and good quality Mod to high cellularity and good quality Mod cellularity and fair quality High cellularity and good quality

DPL-L = Distance between parietal pleura to lesion periphery. DSK-L = Distance between skin surface and lesion periphery. Mod = Moderate. Susp = Suspect. Vma = Volume of mass.

Orthogonal thoracic radiographs (left and right lateral and ventrodorsal views) were available for review in all of the cases. The volume of the pulmonary masses was variable, and average size was 137.2 mL (range, 6.3 to 426.2 mL). The mean DSK-L was 71 mm (range, 37 to 101 mm) and the DPL-L was measured at 33 mm (range, 16 to 71 mm) on average. In most cases, the difference between skin to lesion and pleura to lesion was < 50 mm. However, in 1 case (dog 2) the difference was 60 mm.

After completing the FNA of the pulmonary lesions, no major complications were noted. In the only dog that developed a complication (dog 5), minimal amount of pulmonary tissue (20 mm) had to be traversed to obtain samples. No postprocedure complications were immediately apparent in this patient, and recovery in the ICU was uneventful. The dog was discharged to go home 4 hours after the procedure and, according to the owner, did well in the evening, with no respiratory signs noted. The next morning (20 hours after the procedure), an increase in respiratory rate was noted by the owner. The patient was seen the same morning (22 hours after the procedure), but at the time of presentation the dog appeared eupneic, had a normal pulse oximetry, and no change in Hct was noted when compared to baseline. Repeat thoracic radiographs showed an increase in the radiographic soft tissue density of the mass when compared to the initial radiograph (Figure 2). There was evidence of very mild pneumothorax on the ipsilateral side of the mass noted on ventrodorsal views. The complication was classified as minor since no interventions were required.

Figure 2
Figure 2
Figure 2

Radiographic appearances of the pulmonary mass in dog 5 before fluoroscopy-guided fine-needle aspiration (A) and 24 hours post–fine-needle aspiration (B). Note the difference in radiographic density (black arrows) of the pulmonary lesion.

Citation: Journal of the American Veterinary Medical Association 262, 1; 10.2460/javma.23.07.0413

Cytologic samples were of high cellularity, good quality, and accompanied with significant inflammation in all 4 dogs with carcinoma. Histopathology was only available in 2 dogs (dogs 4 and 5). In dog 4, the cytology was of moderate cellularity and fair quality. Although the lesion was relatively large (86.5 mL), it was deeply seated in the chest cavity (affecting the right accessory lobe). Cytologic evaluation was consistent with probable lymphoma. This diagnosis was confirmed as to be a small to intermediate cell lymphoma on the basis of bronchoscopy-guided biopsies of the airways performed during the same anesthesia. In dog 5, cytologic interpretation was consistent with a suspected carcinoma. The diagnosis was confirmed after partial pulmonary lobectomy was performed, and histopathologic results were consistent with a papillary carcinoma. Computed tomography was performed in only 2 dogs prior to FGFNA because CT was only available after 2016.

Cat data

All domestic shorthair (3/5) and longhair (2/5) cats were included in this study. Three of the 5 cats were female spayed and 2 were male castrated. All cats were 10 years of age or older (mean, 12.4 years; range, 10 to 17 years). Mean weight was 5.0 kg (range, 3.1 to 8.3 kg).

Coughing (60%) and weight loss (40%) were the 2 most common clinical signs reported in these 5 cats diagnosed with pulmonary nodules (Table 2). Vomiting, anorexia, and lethargy were less commonly noted (20%). One cat was asymptomatic (cat 5), and a pulmonary lesion was noted incidentally after orthogonal thoracic radiographs were obtained for staging purposes prior to surgical removal of a tail mass.

Table 2

Description of presenting clinical signs, pulmonary mass volume, sampling distances, complications, and cytologic diagnosis in 5 cats with solitary pulmonary lesions.

Cat 1 Cat 2 Cat 3 Cat 4 Cat 5
Presenting signs Coughing Coughing Coughing Weight loss Asymptomatic
Weight loss Vomiting
Vomiting Lethargy
Vma (mL) 1.6 2.4 3.7 1.8 2.6
Dsk-L (mm) 75 20 37 35 43
DPL-L (mm) 32 12 26 21 15
Complications < 24 h/> 24 h No/No No/No No/No No/No No/No
Exfoliative cytology Necrotic material and calcified debris Chronic neutrophilic inflammation Poss carcinoid with neutrophilic to mixed inflammation Carcinoma with chronic suppurative inflammation Histiocytic inflammation and blood
Sample quality No comments Low to mod cellularity and good quality Mod to high cellularity and good quality High cellularity and good quality Mod cellularity and no comments on quality

Poss = Possible.

See Table 1 for remainder of key.

Orthogonal thoracic radiographs (left and right lateral and ventrodorsal views) were available for review in all the cases. The volume of the pulmonary lesions was variable between cats but considerably smaller than in dogs (2.4 mL; range, 1.6 to 3.7 mL). The mean DSK-L was a little more than 4 cm (42 mm; range, 20 to 75 mm), and the mean DPL-L was measured at 2 cm (21 mm; range, 12 to 32 mm; Table 2). The difference between skin to lesion and pleura to lesion was < 15 mm. However, in cats 1 and 5, this difference was greater (> 25 mm). These cats were classified as being obese and overweight, respectively, on the basis of recorded body condition scores.

No complications postprocedure were reported in this population of cats (Table 2). Compared to dogs, the cellularity of the samples was variable. In 1 cat (cat 1), no comments of the cellularity of the sample were provided because the sample only contained necrotic and calcified material. In 2 (40%) cats, the samples were consistent with inflammation. In cats 3 and 4, the samples were consistent with possible carcinoid and carcinoma, respectively. In terms of cellularity, most of the samples were of good quality (60%), although no comment was given on the quality of the sample in cat 5. No thoracotomies for mass removal were performed in our population of cats. Therefore, correlations between cytologic results and histopathologic results were not made. Computed tomography was performed in only 1 cat prior to FGFNA because CT was only available after 2016.

Discussion

Transthoracic FGFNA was used successfully in these 10 feline and canine patients with deep-seated solitary pulmonary lesions. Complications were infrequent, and a cytologic diagnosis was possible in the majority of cases.

In veterinary medicine, there has been a recent growing interest in the role of minimally invasive techniques for the diagnosis and treatment of various illnesses.15 The primary goal of this manuscript was to describe an updated minimally invasive technique that could be used to sample pulmonary lesions not accessible using more conventional techniques such as transthoracic ultrasound.

Transthoracic FGFNA of pulmonary lesions in our patients appears to be safe irrespective of the size of the mass and the depth of pulmonary tissue traversed to obtain a sample. However, to draw a more meaningful conclusion of the safety of this technique, a larger number of patients would need to be included. FGFNA and biopsies of pulmonary lesions using a 20-gauge Westcott sampling needle has been previously reported in dogs and cats.4 Using this technique, a reported 17% risk of pneumothorax was documented. This complication was predominantly observed in patients with disseminated pulmonary diseases rather than solitary lesions.4 For our patients, cytology samples were obtained using 22-gauge needles, which could have accounted for the low complication rate. Furthermore, the risk of complications did not increase with smaller nodules or the length of normal pulmonary tissue traversed as it has been often reported in human medicine.16 In fact, only 1 minor issue was observed in 1 dog (dog 5). The thoracic lesion in this patient was the largest reported in this study and located relatively close to the thoracic wall (2 cm). The cause for this complication was not fully determined, but mild hemorrhage as well as release of inflammatory cytokines leading to tissue edema were suspected to be the primary cause of the clinical and radiographic changes. In cats, the pulmonary lesions were relatively small in comparison to those in dogs; however, none of the cats developed complications. The results of our study parallel those of humans in which FNA with a 22-gauge needle appeared to be associated with a lesser degree of procedural complications.16 However, to reduce type II errors, a larger number of patients would need to be included in this study to statistically assess the correlation between complications, the size of pulmonary nodules, and the length of pulmonary tissue traversed.

In dogs, transthoracic FGFNA appears to provide cytologic samples that were of diagnostic quality. In all dogs with suspected pulmonary carcinoma, the samples were of good quality and moderate to high cellularity irrespective of the size of the mass or the distance needed to be traversed to reach the lesion. To fully ascertain the accuracy of this technique, correlation between cytologic and histopathologic diagnoses would have been required. However, our results appear to be consistent with other studies in which transthoracic ultrasound-guided FNA of pulmonary lesions ranged from 80%17 to 91% accuracy with 100% positive predictive value.1 In a 1988 study4 evaluating transthoracic FGFNA biopsy of diffuse and discrete thoracic lesions in dogs and cats, cytologic results were consistent with histopathology results in 37 of 44 cases. However, using this technique for the sampling of solitary pulmonary lesions, cytologic and histopathologic results were correlated at 100%.4 Although inflammation can cause epithelial cell atypia that can mimic criteria of malignancy, primary inflammation can often be distinguished from cancer with a reasonable degree of confidence.1,7 In our 1 dog in which lung lobectomy was performed, histopathology confirmed the cytologic diagnosis of carcinoma. In dog 4, the cytologic samples were considered only of moderate cellularity and fair quality. This dog was ultimately diagnosed with small to moderate cell lymphoma on the basis of a bronchoscopic biopsy of a thickened accessory lobe bronchus. One reason for the decrease in sample quality could be attributed to the fact that the lesion was centrally located, making it more difficult to reach. An alternative explanation is that a diagnosis of small to intermediate cell lymphoma is often difficult to make on cytology alone. Histopathology confirmed the cytologic suspicion of probable lymphoma.

The diagnostic accuracy of the transthoracic FGFNA of the lesions in cats may be lower than in dogs. The lack of cytologic diagnosis of carcinoma or other tumor after transthoracic FGFNA in cats was surprising to us since the accuracy of ultrasound-guided FNA has been well demonstrated in dogs as well as in cats.1,18 If the results were to be truly falsely negative, estimated accuracy of this procedure for cats would be 40% at best. This discrepancy in results could stem from the smaller size and more deeply located nature of the pulmonary nodules rendering them more challenging to access.14 Another explanation for this difference in cytologic accuracy could be that 2 of the 5 cats (cats 1 and 5) had high body condition scores, which increased the distance to access the pulmonary lesion. Yet it is also possible that solitary pulmonary nodules in cats are not as sinister in nature, compared with those in the dog. In our study, for the 3 cats (cats 1, 2, and 5) that had samples consistent with necrotic tissue or inflammation, survival times were 36, 18, and 26 months, respectively. When compared to cats in which FNA results were consistent with carcinoma, cats with inflammatory/necrotic lesions survived 6.3 times longer (798 vs 126 days). In 1 cat (cat 1), thoracic radiographs were serially performed and pulmonary mass size remained static. The reported survival time in cats with pulmonary carcinoma without metastatic disease following lung lobectomy is between 11 and 115 days.19 Hence, the survival time of the 3 cats with “nondiagnostic samples” was not consistent with cats with pulmonary adenocarcinoma. In addition, at the time of diagnosis, 30% to 53% of cats with pulmonary carcinoma have evidence of intrathoracic metastatic disease8,20 while 16% have extrathoracic metastases.21 In our study, none of the cats had evidence of intra- or extrathoracic metastatic disease. Therefore, in cats, a solitary pulmonary nodule has the potential to be benign in nature. This strengthens the argument that sampling should be performed prior to contemplating surgical options.

There were several limitations in this study inherent to its retrospective nature. Confirmation of cytologic diagnosis with histopathologic results was only available in 2 cases. In retrospect, bacterial cultures should have been performed on all the samples obtained. This seems to be even more important for cats in which results are often inflammatory in nature. The risk of complication was low in our study (10%) and only considered mild. However, monitoring of our patients was only performed immediately after sampling the thoracic lesions. Therefore, postoperative complications that may have occurred a few hours after the procedures may have been missed and therefore underestimated in our study.4

In conclusion, we describe an updated technique using fluoroscopy to aid in the diagnosis of pulmonary lesions in dogs and cats. The technique appears safe and accurate irrespective of the depth or size of pulmonary lesions. In dogs, transthoracic FGFNA of a solitary pulmonary lesion is highly accurate. In cats, this technique seems to be reasonably accurate. However, further studies with a larger population of patients need to be undertaken to better characterize the accuracy of this technique in cats and dogs. In addition, correlating the cytologic diagnosis with histopathology is paramount to fully assess the precision of this procedure.

Acknowledgments

None reported.

Disclosures

The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.

Funding

The authors have nothing to disclose.

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