A novel needle guide system to perform percutaneous laser ablation of liver tumors using the multifiber technique

Abstract

Background

Previous studies have shown that laser ablation with the multifiber technique is effective in the treatment of liver tumors. However, the correct positioning of multiple needles may be challenging.

Purpose

To investigate the use of a novel needle guide system that was developed to perform percutaneous laser ablation of liver tumors with the multifiber technique under ultrasonographic guidance.

Material and Methods

Between February 2009 and June 2011, 116 patients (104 hepatocellular carcinomas and 12 metastases) with 127 liver nodules (median diameter, 3.0 cm; range, 1.5–6.0) were treated. Nineteen nodules were in high-risk locations. A needle guide with separate channels to insert two needles in a parallel position and at a prefixed distance was used.

Results

Needles were positioned inside the target nodule easily and quickly, and correct spacing (1.5–1.8 cm) between light sources was immediately achieved. Complete tumor ablation was achieved in a single session in 112 (88.2%) lesions. In nodules ≤3.0 cm and >3.0 cm in size, ablation was complete in 93.6% and 79.6% of cases, respectively. Of note, complete ablation was achieved in 91.7% of nodules up to 5.0 cm.

Conclusion

With the new guidance system, needles could be inserted in parallel fashion, which facilitated positioning the needles in geometrical configurations to maximize the ablative effect. Worthy of note, the complete ablation rate in nodules >3.0 cm using the new guide system was higher than what has been reported in the literature so far.

Keywords

Ablation procedures laser liver ultrasound

Over the last two decades, image-guided percutaneous ablative therapies have gained popularity as an effective and safe alternative to surgical resection in patients with primary and secondary liver cancer (1, 2). Among these minimally invasive therapies, radiofrequency ablation has become the most clinically accepted and is currently the most widely used technique (3). However, some studies have shown that laser ablation (LA) may be as effective and safe as radiofrequency ablation (4 –10). The term LA refers to the thermal destruction of tissue by conversion of absorbed light into heat. Laser energy is faster and less tissue-sensitive than radiofrequency energy (11), but light scattering and absorption and tissue carbonization decrease energy penetration, thereby limiting the size of the necrotic zone. Therefore, multiple fibers or fibers with a cooled diffuser tip are used. The first consists of firing multiple bare fibers spaced 1.5–1.8 cm apart throughout a target lesion (9, 12 –15), while the second uses cooled-tip diffuser fibers that can deposit up to 30 W over a large surface area, thus diminishing local overheating (16 –22). With multiple bare fibers technique, two to four 21-gauge needles are positioned, depending on the size, shape, and location of the lesions; when four fibers are used, they should be positioned in the area to be treated so that a square configuration is achieved as much as possible. The needles are positioned one at a time through the single skin entry port. Two fibers are used for lesions ranging in size from 1.0 to 2.0 cm, and four fibers for larger lesions. The use of fine needles and ultrasound (US) guidance allows a safer and more flexible approach even through the intercostal route. By tilting the US probe, fibers can be arranged according to the lesion shape. Further, the insertion of four needles in a sequential fashion increases the accuracy of the treatment (23). In most cases, no more than two illuminations are performed during the same session (pull-back technique). For each illumination, the laser is turned on at a power of 5.0 W with an exposure time of 360 s (1800 Joules [J] per fiber). Fibers are always activated simultaneously (13). However, inserting multiple needles may be challenging for less experienced operators, resulting in longer operative times and in less reproducibility of the technique. In addition, when treating large lesions with pull-back technique, the distance between the laser sources was not maintained and the ablative zone expected is obviously smaller than what could be achieved if the applicators were correctly spaced 1.5–1.8 cm apart (13). In fact, a multicenter study reported that complete ablation rate dropped from 85.1% for nodules ≤2.0 cm to 60.4% for nodules ranging in size from 3.1 to 4.0 cm (9), reflecting both inter-operator variability and the limits of the pull-back technique based on single skin entry point. To overcome these limitations, we used a novel guidance system to make placement of multiple needles into tumors easy and precise in order to maximize the ablative effect, especially when the pull-back technique is necessary to treat larger nodules. This study was designed to evaluate the use of this needle guide in performing LA ablation of liver tumors.

Material and Methods

Patients

This prospective study was approved by our institutional review board. From February 2009 to June 2011, 121 previously untreated patients were evaluated for LA. Naive patients with hepatocellular carcinoma (HCC) or liver metastasis who were not candidates to surgical resection or who refused surgery were considered for enrolment in the study. One hundred and four patients had HCC and 12 had liver metastases (one breast, one lung, one pancreas, and nine colon). Nineteen nodules were in high-risk locations as previously defined (24 –26): 14 were adjacent to extrahepatic organs (eight subcapsular and six with exophytic growth), two to bile ducts, and three to vascular structures. Baseline patient characteristics are shown in Table 1. HCC diagnosis was made according to the European Association for the Study of the Liver guidelines (1). The diagnosis of metastasis was confirmed by liver biopsy. LA was considered as a therapeutic option if the patient had a single nodule ≤6.0 cm in diameter or no more than three nodules with the sum of the diameters ≤6.0 cm. The exclusion criteria were as follows: (i) Eastern Cooperative Oncology Group Performance Status ≥1; (ii) liver failure; (iii) severe coagulopathy (platelet count <40,000/mmc; INR >2.0); (iv) extra-hepatic metastases; (v) thrombosis of the main portal trunk/main portal branches or main hepatic veins; and (vi) severe co-morbidity. The size and number of lesions, their location in the liver, and vascular and biliary ingrowth were established in all patients by US and computed tomography (CT) or magnetic resonance imaging (MRI). Median nodule diameter was 3.0 (range, 1.5–6.0) cm in HCC patients and 2.8 (range, 1.5–6.0) cm in patients with metastasis. All patients gave their informed consent to participate in the study.
Table 1
Baseline patient characteristics

Characteristic Value

Male, n (%) 80 (69)

Age, median (range) 65 (35–80)

Etiology, for cirrhotics only, n (%)

HCV 80 (76.9)

HBV 10 (9.6)

HCV + alcohol 8 (7.7)

Alcohol 6 (5.8)

Child-Pugh score, for cirrhotics only, n (%)

5–6 84 (80.8)

7 20 (19.2)

Tumor size (cm), median (range) 2.9 (1.5–6.0)

Tumor size (cm), n (%)

≤2.0 29 (22.8)

2.1–3.0 49 (38.6)

3.1–4.0 28 (22.1)

4.1–5.0 15 (11.8)

5.1–6.0 6 (4.7)

Nodules, n (%)

1 107 (92.2)

2 7 (6.1)

3 2 (1.7)

Technique

A commercially available system (Echolaser, Elesta Srl, Florence, Italy) composed of an US device and a laser unit was used. The laser source was a semi-conductor diode with a wavelength of 1064 nm. A single flat tip bare optical fiber measuring 300 µm in diameter was inserted through a 21-gauge needle. The needle guidance device for use with a US transducer was made up of a reusable frame for housing the transducer and a disposable snap-on needle guide. This device is commercially available (Elesta Srl, Florence, Italy). The needle guide had separate channels so that two needles could be inserted in a parallel position and at a prefixed distance (Fig. 1); on the US machine screen, dotted lines displayed needle paths with an angle of 15° or 30°. The first needle was introduced through the channel of the guide nearer to the ultrasound probe. The second needle was inserted in a separate parallel channel positioned at a distance of 1.5–1.8 cm from the first. After positioning the needles, the guide was released from the probe and the procedure was repeated to place another pair of needles. According to the nodule volume and shape, up to eight needles were used. In cases of nodules up to 2.0 cm in diameter, two fibers delivering 3600 J in 6 min were usually used (13). For nodules up to 3.0 cm, four fibers arranged in a square configuration with a side-length of 1.5–1.8 cm and a single illumination for 6 min (delivering 7200 J) were used (Figs. 2 and 3) (13). In cases of nodules >3.0 cm, four to eight needles and the pull-back technique were employed; treatment lasted up to 24 min and delivered up to 28,800 J. More than four needles were also used in patients with multiple liver nodules. For example, in a patient with a lesion ≤6.0 cm in diameter with two synchronous lesions of 2.0 or 1.0 cm in size in different locations, we positioned four, two, and one laser source, respectively. In a single session, we illuminated the first four simultaneously with pull-back technique in the largest lesion, then the second two to treat the 2.0 cm nodule, and finally, the single source for the smallest lesion (Fig. 4). All needles were positioned before starting LA so that any gas caused by the treatment would not prevent the correct positioning of the needles. At the end of the treatment session, the still-illuminated fibers were withdrawn to induce hyperthermia along the needle tract in order to avoid neoplastic seeding. The procedure was performed under conscious sedation.
Fig. 1
Convex ultrasound probe with lateral-mounted needle guide

Fig. 2
Ultrasound image of four illuminated fibers inserted in a 3.0 cm nodule

Fig. 3
Four needles inserted to treat a 3.0 cm nodule: (a) by abdominal route; (b) by intercostal route

Fig. 4
Eight needles inserted: (a) by abdominal route, to treat simultaneously a 3.0 cm nodule and two 2.0 cm nodules; (b) by intercostal route, to treat a 5.0 cm nodule

Assessment of treatment efficacy

Four weeks after LA, the treatment response was assessed by dynamic contrast-enhanced CT or MRI. Imaging studies were evaluated by two independent observers (GGDC and GDA). The response was defined as complete ablation when no areas of enhancement were seen within or at the periphery of the ablation zone. We considered a patient successfully ablated if complete response was confirmed at 6 months after the first ablation. Although additional LA sessions to ablate the tumor were theoretically possible, a time limit of 6 months was considered reasonable to make a final assessment on the effectiveness of LA.

Follow-up

Patients who had a complete ablation after LA treatment underwent follow-up studies, including clinical assessment, measurement of liver function and AFP levels, US examination every 3 months, and CT or MRI every 6 months. Local tumor progression (LTP) (27) was defined as the presence of enhancement foci contiguous (<2 cm) or within the treatment area in one imaging modality (either CT or MRI) on follow-up.

Assessment of complications

Complications of treatment were categorized following the reporting standards of the Society of Interventional Radiology (SIR) (28). Minor complications included two categories: (A) No therapy, no consequence; (B) Nominal therapy, no consequence; includes overnight admission for observation only. Major complications included four categories: (C) Require therapy, minor hospitalization (<48 h); (D) Require major therapy, unplanned increase in level of care, prolonged hospitalization (>48 h); (E) Permanent adverse sequelae; and (F) Death.

Statistical analysis

Quantitative variables were expressed as mean, standard deviation, median, and 95% confidence interval (CI); qualitative variables as absolute number and percentage. The main endpoint of the study was complete tumor ablation. Kaplan-Meier method was used to calculate the time to local tumor progression. Only results with P value <0.05 were considered statistically significant. Data were analyzed with the IBM SPSS Statistics release 20.0 (SPSS Inc., Chicago, IL, USA).

Results

In five (4.1%) of 121 patients the procedure was unfeasible due to the poor visualization of the nodule on US. Therefore, 116 patients with 127 cancer nodules received LA. Median released joules were 7500 (range, 1800–28,800). The number of needles used was two in 25 cases, four in 72 cases, six in six cases, and eight in 13 cases (in seven for a single large nodule and in six for multiple nodules). After a single treatment, complete ablation was achieved in 112 (88.2%) nodules (Fig. 5). LA effect was not evaluated in the patient who died of variceal bleeding 1 month after procedure. A complete ablation was observed in 87.6% of HCC nodules and in 92.9% of metastases. In nodules ≤3.0 cm and >3.0 cm in diameter, ablation was complete in 93.6% and 79.6% of cases, respectively. In particular, complete tumor ablation after a single session was achieved in 91.7% of nodules up to 5.0 cm in size (Table 2). Complete ablation of all nodules in high-risk locations was achieved. Mean follow-up was 14.8 ± 6.5 months. At the time of analysis, LTP was observed in 18 (16.1%) of 112 nodules. Mean diameter of nodules with and without recurrence was 3.2 cm and 2.9 cm, respectively (P = 0.166). The mean LTP time was 26 months (95% CI, 24–28) in HCC patients and 12 months (95% CI, 11–12) in patients with metastasis.
Table 2
Complete ablation rate according to nodule size

Nodule diameter (cm) Complete ablation, n (%)

≤ 2.0 29/29 (100)

2.1–3.0 44/49 (89.8)

3.1–4.0 25/28 (89.3)

4.1–5.0 13/15 (86.7)

5.1–6.0 2/6 (33.3)

Fig. 5
Four weeks after LA, MRI scan shows complete ablation of a 5.0 cm HCC located in the VI liver segment, with no detectable areas of enhancement in the tumor

After treatment, 34% of patients experienced moderate pain that did not require hospitalization (SIR class A) and 60% of patients had self-limiting fever lasting no more than 15 days (SIR class A). One case of subcutaneous tumor seeding (SIR class C) along the needle track was observed. The nodule was surgically removed and the patient is still disease free 18 months after the procedure.

Discussion

LA for liver tumors has been proven safe and effective (5, 9) and could be considered an effective alternative to RFA (10, 23, 29). In this study we used the Pacella technique (13, 23), which involves the use of multiple flat tip thin bare optical fibers. In-vitro studies have shown that simultaneous treatment with four fibers positioned in a square configuration with a side-length of 2.0 cm produced lesions that were 11 times bigger than those produced with a single fiber, creating an ablation area 4.0 × 3.0 cm in size (30, 31). Therefore, proper fiber placement inside the tumor is important for successful treatment. This treatment modality has a steep learning curve, which may severely affect operators' complete ablation rate after LA treatment (32). The novel needle guide was developed to overcome this limitation: two parallel needles are inserted simultaneously, resulting in simplified needle positioning and more uniform spacing between light sources. Furthermore, this guide allows the insertion of multiple needles through two adjacent intercostal spaces. Since needle insertion was easier and quicker, we were able to position up to eight needles before starting LA without increasing complication rates. In this regard, the present study did not differ from those reported in the current literature on LA (8 –10), since no death was recorded and only minor complications were observed. Theoretically, our novel guide system could reduce both the operator learning curve and the inter-operator variability in ablative rate after LA. Further studies addressing this point specifically are necessary.

After a single session, complete tumor ablation was achieved in 91.7% of nodules up to 5.0 cm in size and in all nodules in high-risk locations. These results are better than those reported in previous published studies evaluating LA with multiple thin optical fibers (9, 13), especially when considering nodules >3.0 cm. In the most recent multicenter study by Pacella et al., complete ablation rate dropped from 85.1% for nodules ≤2.0 cm to 60.4% for nodules between 3.1 and 4.0 cm (9). Although historical comparisons should be considered cautiously, our better ablative effectiveness in larger nodules might be explained by the fact that inter-needle spacing was maintained throughout pull-back maneuver, thereby allowing a wider and more uniform diffusion of energy. Instead, in the original Pacella's technique, (12, 13) the pull-back maneuver entailed a variable reduction of the distance between needles (hence of the ablative area) since the needles are inserted through a single skin entry.

Other groups have used MRI guidance, which allows real-time thermal mapping, to perform LA, thereby permitting the operator to visualize size and temperature of the ablative zone (18, 33 –36). The interest in MRI-guided ablation is growing, as its high-quality images make high-sensitivity tumor detection possible, as well as accurate identification of the target region with multiplanar imaging. Hence, LA treatments may be performed in real time under MR guidance using fast gradient echo sequences (21, 37). MR monitoring has great clinical advantages but the use of an efficient US guidance would be much more convenient and accessible and far less expensive and cumbersome. The US-guided needle placement technique used in this study is quick and easy, and operators performing US-guided biopsies may find this technique very similar. Further, treatment assisted by the new guidance system was safe, with only minor complications occurring even after treatments that lasted up to 24 min and/or that employed more than four needles.

In conclusion, the new needle guide system for LA of primary and secondary liver tumors under US guidance makes it easier and quicker to position of multiple laser fibers and seems to improve ablative effectiveness in tumor nodules >3.0 cm, where the pull-back technique is necessary.

Characteristic	Value
Male, n (%)	80 (69)
Age, median (range)	65 (35–80)
Etiology, for cirrhotics only, n (%)
HCV	80 (76.9)
HBV	10 (9.6)
HCV + alcohol	8 (7.7)
Alcohol	6 (5.8)
Child-Pugh score, for cirrhotics only, n (%)
5–6	84 (80.8)
7	20 (19.2)
Tumor size (cm), median (range)	2.9 (1.5–6.0)
Tumor size (cm), n (%)
≤2.0	29 (22.8)
2.1–3.0	49 (38.6)
3.1–4.0	28 (22.1)
4.1–5.0	15 (11.8)
5.1–6.0	6 (4.7)
Nodules, n (%)
1	107 (92.2)
2	7 (6.1)
3	2 (1.7)

Nodule diameter (cm)	Complete ablation, n (%)
≤ 2.0	29/29 (100)
2.1–3.0	44/49 (89.8)
3.1–4.0	25/28 (89.3)
4.1–5.0	13/15 (86.7)
5.1–6.0	2/6 (33.3)

Footnotes

Conflict of interest: None.

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