www.impactjournals.

com/oncotarget/ Oncotarget, Advance Publications 2016

Percutaneous laser ablation: a new contribution to unresectable

high-risk metastatic retroperitoneal lesions?
Tian’an Jiang1, Zhuang Deng2, Guo Tian3,4, Fen Chen2, Haiwei Bao2, Ju Li2 and
Weilin Wang2,4
1
Department of Ultrasound Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine,
Hangzhou, China
3
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University
School of Medicine, Hangzhou, China
4
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang
University School of Medicine, Hangzhou, China
Correspondence to: Weilin Wang, email: [email protected]
Keywords: laser ablation, ablation, retroperitoneal tumor, lymph nodes, oncology
Received: July 25, 2016 Accepted: November 22, 2016 Published: December 10, 2016

ABSTRACT
BACKGROUND & AIMS: Metastasis in retroperitoneal lymph nodes is one of the
signs of advanced stage or terminal stage of malignancy. We performed a trial to
assess the safety and efficacy of ultrasonography (US)-guided local neodymium-doped
yttrium aluminum garnet (Nd:YAG) laser ablation for metastatic lymph nodes in the
retroperitoneal region.
METHODS: We evaluated 4 cases of retroperitoneal metastatic lymph nodes
treated using US-guided Nd:YAG laser ablation. Additionally, we reviewed the PubMed
database for articles on thermal ablation of retroperitoneal lesions until March 2016,
without language limitations.
RESULTS: In our study, all lesions were nearly completely ablated with mild
discomfort, including pain and fever at the 3-month follow-up. In the literature
review, a total of 398 patients with 491 retroperitoneal tumors were identified, and
complications after the procedure included enterovesical fistula, fecal incontinence,
and hematoma.
CONCLUSIONS: Percutaneous laser ablation could be a theoretically promising
approach for retroperitoneal metastatic lesions. ClinicalTrials.gov number:
NCT02822053.

INTRODUCTION vessels behind, can cause serious complications after

injury, including death. Moreover, unintentional injury
Local ablation of tumors has been shown to have a of the great vessels might result in fatal hemorrhage.
good curative effect [1-6]. The common ablation therapies Neodymium-doped yttrium aluminum garnet (Nd:YAG)
for abdominal metastatic tumors include radiofrequency laser ablation allows for accurate thermal field control,
ablation (RFA) [7, 8], microwave ablation (MWA) and it uses a 21-G fine needle and can penetrate the
[9], and ethanol injection (EI) [10], cryoablation [11], gastrointestinal tract. The adventages of the small needle
irreversible electroporation (IRE) [12] and high-intensity and precise thermal energy distribution theoretically
focused ultrasound (HIFU) [13]. Nevertheless, metastatic could minimize the risk of off-target burning and decrease
retroperitoneal lesions are a rare group of neoplasms with problems in treating lymph nodes and particularly in
usual anatomical complexities, which raise challenges for difficult anatomical location. Previous studies have
radical resection. If tumors are located near great vessels, focused on laser ablation in the prostate [14, 15], thyroid
the heat effect is impaired. Additionally, retroperitoneal [16-19] and liver [20, 21] while the present study aimed
deep tumors, which have important structures, such to assess the safety and efficacy of ultrasonography (US)-
as the gastrointestinal tract, in front and large blood guided local Nd:YAG laser ablation for metastatic lymph

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 Table 1: Details of the patients’ history, PLA procedure and follow-up

M: Man;
CT: Computed Tomography
MR: Magnetic Resonance
PTA: Percutaneous laser ablation;
PR: Partial response;
CR: complete response;
CEA: Carcinoembryonic Antigen;
AFP: Alpha Fetoprotein;
CA19-9: Carbohydrate Antigen 19-9.

nodes in the retroperitoneal region. Additionally, we images showed a hyperechoic area around the fiber tip.
performed a systematic review of the literature. It was obtained after a delay about 80-120s. Then the
hyperechoic region expanded slowly forward. When the
RESULTS procedure finished, the whole lesion was covered with
hyperechoic zone. There were no major complications
In our study, the lymph node in 15-40 mm in size detected in the patients during the laser ablation. All the
using 2 laser fibers. The total energy was between 2600 pre-admission symptoms like abdominal pain, weakness
J and 3600 J. During laser energy application, ultrasound have relieved. The detailed information during ablation
was listed in Table 1.

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 Case 1 had only single ablation with US guidance went back to normal without drug intervention. After the
using two laser fibers due to gallbladder carcinoma initial laser ablation in case 2, CEA and CA19-9 levels
metastatic retroperitoneal lymphoma, and he had decrease were also declined. Two-week follow-up arterial phase of
in CEA and CA19-9 levels while AFP level was in enhanced MRI revealed necrosis area of 3.2*2.3 cm, but
normal. The contrast-enhanced CT obtained 3 months 6 weeks later substance phase of contrast-enhanced CT
after ablation showed mostly response (Figure 1). During scan showed the increased peripheral tumor 4*3.1 cm in
the follow-up period, case 1 had fever for two days and size and decreased necrosis area 2.3*1.8 cm (Figure 2).

Figure 1: Metastasis of lymph nodes in a 60-year-old man who had undergone gallbladder cancer resection. MR
image of T2-weighted and substance phase showed enlarged, round lymphoma around retroperitoneal abdominal aorta a.,b. (arrowhead).
Preoperative US image revealed a hypoechoic mass 2.52*2.26 cm c.. Intraoperative sonogram showed the one d. (arrowhead) and two
needles e. (arrowhead) inserting into the tumor, suggesting the distances (cm) of needle tip to tumor margin (anterior: 1.61; 1.54). Afterwards,
the mass had local enhancement under ultrasound scanning f., and increased unenhanced low-density areas in arterial g. (arrowhead) and
substance phase h. (arrowhead) on contrast-enhanced CT scan.

Figure 2: A 43-year-old man with metastatic lymph nodes originating from liver cancer. Axial contrast-enhanced MR image
was obtained at the abdominal setting. An oval, mildly high signal intensity is present close to aorta abdominalis a. (arrowhead). Preoperative
CEUS images showed the lesion with rapid wash-in and wash-out in arterial b.. Axial gray-scale US image indicated intraoperative ethanol
ablation c.. Before initial laser ablation, the mass is shown in the retroperitoneum under US guidance d.. Two laser fibers parallelly ablated
the tumor under the guidance of US, which appraised the distances (cm) of needle tip to mass boundary e. (anterior: 1.9; 1.8; left: 0.9; right:
0.7), and subsequent immediate CEUS image showing a large and central filling defect f..

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 Table 2: Summary of 398 cases with 491 retroperitoneal tumors after ablation in 18 published literatures
Follow-up
Treatment Patients(No. Tumor Male/ Mean
Author Year Country Characteristics of patients interval Prognosis Complication
method of tumors) size(cm) female age(range) (months)

Retroperitoneal No evidence of 1 perirenal

65.4 (35– 16.2
Gill IS et al. 2000 America Small renal masses laparoscopic 32(34) 2.3 NA local or port-site hematoma;1
93)
cryoablation recurrence herpes esophagitis

7 patients with unresectable 1 enterovesical

Machi J recurrent retroperitoneal or pelvic US-guided RFA 5.05 73 Local recurrence fistula;1 skin
2003 America 7(11) 5/2 24
et al. tumors from colorectal (n=4), renal (2.9-10) (62-83) rate: 16.7% burn;1 fecal
(n=2), and prostate (n=1) incontinence

5 elevated
amylase;
Retroperitoneal remained and lipase levels;1
1
Lee DI et al. 2003 America Small renal masses laparoscopic 20(20) 2.6±0.8 11/9 67.9±13.4 14.2 electrocardiogram
unchanged
cryoablation changes;1 atrial
fibrillation;1
pancreatic injury
Percutaneous
1 metastatic left adrenal tumor from CT-guided
Kariya S 67 Completely
2005 Japan primary lung cancer;1 left renal cell RFA with 2(2) 5.5*3.8 ;3 2 1 week Pain
et al. (62-72) response
carcinoma percutaneous
CO2 injection
Percutaneous Completely
Keil S et al. 2008 Germany 1 retroperitoneal liposarcoma 1(1) 2.3*2.2*3.6 1 65 27 NA
CT-guided RFA response

Patel MN Robot-assisted No evidence of

2008 America Right posterior renal hilar mass 1 3.6 1 74 4 No
et al. cryoablation tumor recurrence

5 completely
response and 2 of
Arellano RS 3 ovarian carcinomas; 5 endometrial Percutaneous 2.1 69.1 these five died of NA
2010 America 8(8) NA 23.5
et al. carcinomas CT-guided RFA (1.0-3.7) (59-77) metastatic disease
at 9 and 13 months;
2 failed

Orgera G Hilar hepatic node from breast HIFU Completely

2010 Italy 1(1) 3 0/1 60 8 NA
et al. cancer metastasis response

Complete
removal:74.5%;1-
Wan ZH 2011 56
China Primary retroperitoneal sarcoma HIFU+Surgery 47(47) NA 26/21 60 year recurrence 27 pain
et al. (28-76) rate:40.4%;5-year
OS:68.1%
1-year OS:
a)26.3%;b)7.7%;the
a)19 local control rate 2
retroperitoneal metastatic lymph Percutaneous a.19(19); a.2.2±0.1; a.15/4; a.57.3±2.3; 9
Gao F et al. 2012 China of 3, 6, 10, and 15 pain hematoma;2
nodes from hepatocellular carcinoma CT-guided RFA; b.13(13) b.2.1±0.2 b.10/3 b.52.1±2.9 (3-15) months: a)78.9%,
b)13 only RFA 73.3%, 41.7% and
25.0%

11.5*15;
Zhao M Percutaneous 36 Completely
2012 China retroperitoneal schwannoma 2(3) 7*7; 0/2 60; 27 Pain
et al. CT-guided RFA (22-50) response
4.8*4.4

Percutaneous 12 total local

Littrup PJ 2013 CT- and/or 47(75) 60.4 (18.4- 9 recurrences;average 13
America 75 retroperitoneal soft-tissue tumors NA NA
et al. US-guided 91.7) (0-82) time to recurrence:
cryotherapy 5.5 months

Araujo LH Percutaneous Completely

2013 Brazil Metastatic leiomyosarcoma 1(1) 5.1*4.7 0/1 47 18 NA
et al. CT-guided RFA response

Recurrence of urothelial carcinoma Percutaneous

Molina R 2014 Completely
Spain of the upper urinary tract after CT-guided RFA 1(1) 3.1 1 73 24 No
et al. response
nephroureterectomy

Narayanan Primary and metastatic IRE No evidence of 2 portal vein

2014 America 101(129) 2.7±1.5 56/45 24–83 10.3
G et al. tumors in different organs tumor recurrence thrombosis
All completely
6 percutaneous
Monfardini Local recurrence of renal cancer RFA; 2 8(16) 1.65 59 11.7 (7- response;local free 1 abdominal
2015 Italy 7/1 progression
L et al. after surgery laparotomic (0.7-3.4) (43-77) 16) survival time:11.3 fistula
RFA months
Median PFS: 37.0 ± 19 fever;11 local
Recurrent retroperitoneal soft tissue CT-guided 49 7.7 months;median pain;10 emesis;6
Fan W et al. 2016 China 72(94) 1.29±0.42 29/43 45
sarcoma cryoablation (25–86) OS:43.0 ± 5.9 frostbite;1 nerve
months injury

10 margin 1 urinary
Underhill Locally advanced pelvic and IRE 54 enhancement;4 retention and
2016 America 15(15) NA 8/7 3
CE et al. retroperitoneal tumors (23-74) tumor ablation;1 leg paresthesias;1
palliation foot drop

CT: Computed Tomography; RFA: Radiofrequency ablation; CR: complete response; PFS: progression-free survival; OS: overall survival;
NA: Not available.

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 Subsequently another ablation was performed and three concentration still beyond reference value. Three-month
months later MR scan indicated that the size of peripheral follow-up MRI or CT scan showed the lymph nodes
and necrosis area successfully reduced to 2.9*2.8 cm and were considered as complete response for decreasing
2.5*2.2 cm, respectively (Figure 3). In this study, case enhancement about 80% (Figure 4). In addtion, case 4
3 repeatedly adopted four US-guided laser ablations in underwent one laser ablation. His tumor markers were all
two months due to the residual lesions. CEA, AFP and in normal for pre-and post-ablation. One month later, MRI
CA19-9 levels were all decreased but postoperative AFP indicated the lesion was complete necrosis (Figure 5).

Figure 3: Axial abdominal MR image performed 13 days after initial ablation revealed the peripheral remanent tumor
a. (white arrows), 6-week follow-up CT scan of the venous phase measuring 4*3.1 cm with area of central necrosis 2.3*1.8 cm b. (white
arrows). Before the second laser ablation, a central well-defined hyperecho surrounding unenhanced hypoechoic active areas c.. During
ablation, immediate US scan showed the left part of tumor obvious enhancement d., and the next day a finding that most response appeared
e., f.. At a follow-up visit 11 days, a contrast-enhanced CT venous phase image revealed the enlarged areas of tumor necrosis g. (white
arrows). Then two months later, there was reduced mass necrosis of 2.43*1.7 cm at T1 h. (white arrows), T2 i. (white arrows) and substance
phase j. (white arrows) of MR image.

Figure 4: A 60-year-old man with metastatic lymph nodes close to the duodenum, pancreas, stomach and blood vessels.
Preoperative T2-weighted a. (white arrows), substance phase MR scan indicated a tumor close to the hepatic portal vein, pancreas and
stomach b. (white arrows). Axial US image of the retroperitoneal region showed the mild hyperechoic area c. (white arrows). After fourth
ablation, US image showed the lesion had complete response d. (white arrows). Substance phase of CT obtained 3 days after US-guided
PLA revealed no signs of malignancy e. (white arrows), and then one month later, substance phase of MR image has low signal intensity f.
showing complete necrosis of the tumour (white arrows).

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 In addition, we carefully conducted a systematic 14- to 17-gauge, which could be easily bleeding. As we
review using keywords of retroperitoneal, tumor, ablation, know the retroperitoneal lymph node is seated in deep
cryoablation, electroporation and high intensity focused position. In front of them, there are bowels, stomach,
ultrasound by searching from PubMed, Scoups and Web pancreas, or liver. If the electrode passes through these
of science ahead of October 2016 without language structures, severe complications will occur. Furthermore,
limitations (see Appendix 1). The summary of 398 cases the lymph nodes are adjacent to abdominal aorta and
with 491 retroperitoneal lesions from 18 studies was inferior vena cava, which are risky that can’t be harmful.
presented in Table 2 [7, 8, 12, 13, 22-35]. The mean age of Thus these make the treatment difficult. Some studies
these studies was above 36, and 55.3% were males. reported that CT-guided interventional therapies were
conducted, whcih could provide precious position of the
DISCUSSION puncture needle and the retroperitoneal tumors [8, 28].
Ablation in the prone position could avoid anterior bowel
Metastasis in retroperitoneal lymph nodes is difficult loops and vascular structures under CT guidance [36, 37].
to treat, which is one of the signs of advanced stage or But sometimes it could be forbidden in CT examination
terminal stage of malignancy. The metastatic lymph nodes when the lymph node was covered by some important
are often multiple, surrounded by large vessels, close regions like the bowel. In this study, ultrasonography
to celiac nerve. These features lead to difficult excision could freely guide the needle into the deep position from
for them. The routine treatments of these patients are more angles. So it was feasible to keep the needle away
chemotherapy or radiotherapy. But some of the tumors are from the vessels and organs. In addition, in recent years,
not sensitive to these therapies and many patients in this real-time fusion imaging of US and preoperative CT or
period are in poor general condition, who can’t tolerate MRI images has been considered to be helpful in targeting
the treatment procedure. Successful local inactivation tumors in complex and delicate anatomical area [38, 39],
of these lymph nodes can prolonged survival in patients which could be a promising way to focus on this disease.
[7, 28]. Previous studies about thermal ablations such as Laser ablation is one of the thermal therapies that
percutaneous CT and/or US-guided RFA, cryotherapy of used for local control of malignant tumor. In this study,
the retroperitoneal tumors showed that the complications we used ultrasonography to guide the inserting of Nd:YAG
usually occurred in postoperation [7, 8, 12, 13, 22-35]. laser fiber and no major complications occurred. It was
While the diameter of the electrode used in RFA is usually a theoretically good adjuvant tool because it enabled the

Figure 5: A 60-year-old man with metastatic lymph nodes beside the inferior vena cava. Preoperative MR image in T2-
weighted a. (white arrows) and substance phase b. (white arrows) suggested a mass of 3.9*2.1 cm in size close to the vena cava. Then with
the guidance of US, two laser fibers parallelly were insered into and ablated the tumor c.-e. (white arrows). One month later, MRI scan
indicated the lesion was complete necrosis f. (white arrows).

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 real-time visualization of the needle and the target lesion. nodes in such patients, in particular without multi-center
The color Doppler imaging allowed the clear identification controlled trials. Thirdly, although we seriously conducted
of the related vessels along the route. Moreover, US-guided laser ablation for retroperitoneal lesions, some
intraprocedural use of CEUS could immediately increase complex critical lesions under single US guidance could
lesion conspicuity and decrease the number of incomplete be still undetectable, and real-time fusion imaging of
treatments and re-treatments. CEUS was regarded as US and CT or MRI images could be applied to identify
accurate as other contrast-enhanced imaging modalities clearer depiction of retroperitoneal anatomical regions in
for the evaluation of technical success after ablation, the future.
which had better cost-effectiveness compared with the Taken together, US-guided percutaneous laser
standard procedure [38, 40]. It was reported the needle ablation could be theoretically promising for unresectable
tract implantation metastases rate from 0% to 4.4% in metastatic retroperitoneal lymph nodes and hepatic portal
RFA [41-43], which enabled coarse needle inserting and lymph nodes, with few complications and a small and
even penetrating into the bottom of the tumor, then needle precise ablation area. However, large-scale studies on
ablation against bleeding and implantation metastases. laser ablation for metastatic retroperitoneal lymph nodes
But in PLA, radiologist used the most fine needle and are necessary to confirm our findings.
slim optical fiber to locate the tip in the shallow tumor,
when finished, retreating fiber to the sheath and the needle MATERIALS AND METHODS
ablation. To date, there has been no report of needle
implantation metastases in PLA. In addition, PLA use During the last 8 months, four patients (4 men, age
YAG laser through optical fiber transmission without range 43-60 years old, mean age 56 years old) suffering
complications of electric injury, vagus nerve excitement from a painful retroperitoneal lymphoma underwent US-
caused by current, and also available in patients with guided laser ablation. Involved primary cancers included 1
severe heart disease, arrhythmia, cardiac pacemaker. gallbladder carcinoma (GC), 3 hepatocellular carcinomas
In most studies, they were reported that the lesion (HCC). The targeted metastatic lymph nodes in the study
close to the great vessels like hepatic vein was likely to were 4 in retroperitoneum (case 1: around abdominal
cause residual tumor because the thermal energy was aorta; case 2: retroperitoneum; case 3: retroperitoneum,
taken away by the blood flow [44, 45]. In this study, these close to the duodenum, pancreas, stomach, blood vessels;
lymph nodes were either close to the aorta, inferior vena case 4: beside the inferior vena cava). This clinical trial
cava or the portal vein. Tumor markers decreased as well. was registered in Clinicaltrials.gov ID: NCT02822053 on
It showed the laser ablation is effective in the lesions of June 20th 2016. The procedure was approved by the ethics
risky positions. The reason may result in that comparing committee of The First Affiliated Hospital of Zhejiang
with the radiofrequency and microwave, Nd:YAG laser University. All authors had access to the study data and
has a shorter wavelength of 1064 nm and higher accuracy have approved and reviewed the final manuscript. All of
of ablation, as well as the characteristics of ultrasonic. As patients have history of partial hepatectomy. Furthermore,
is known to all, the higher the ablation temperature is, the case 2 undergoing two percutaneous ethanol injections
more tissue dehydration, and the stronger coagulability. (PEI) last year, which did not control tumor growth, had
Comparing with other ablations, PLA is a technology a mass in size increased from 2.9*2.2 cm to 3.8*2.9 cm
of higher central and surrounding temperature with low through MR images examination. The basic information of
incidence of splitting or falling off in ablation lesion. It the three patients was listed in Table 1. Lymph nodes size
clinically has the output power of 1 to 7 w but 10 w to (maximum diameter) ranged from 1 cm to 4.0 cm (mean
100 w in RFA and WMA. Several studies reported that 2.9 cm). Patients were symptomatic including experienced
excessive energy input may trigger malignant tumor abdominal pain, weakness and weight lost. Child-Pugh is
recurrence and sharp expansion [46-48]. Therefore, on the an clinically classified standard to quantitatively assess
premise of effectively inactivating tumor, the lower power the liver reserve function in patients with cirrhosis, and
and energy will generate better prognosis. Furthermore, it includes 5 indicators (hepatic encephalopathy, ascites,
laser ablation obtained pathologically and microscopically total bilirubin, serum albumin, and prothrombin time). The
clear and thin boundary between the ablated solidification liver reserve function of different severity of liver damage
area and the surrounding normal tissues while irregular could be assessed using A, B, C levels. Preoperative
and thick using RFA and MWA [49]. Therefore it is and postoperative tumor markers of Carcinoembryonic
theoretically safer when treating the lesions close to great Antigen (CEA), Alpha Fetoprotein (AFP) and
vessels. It meaned that the treatment was of the beneficial. Carbohydrate Antigen 19-9 (CA19-9) levels were
Our results should be noted in view of several measured. In this study, all lymph nodes metastases were
limitations. First, the limited sampling size and the histologically confirmed using US-guided biopsy before
short-term follow-up were noticeable, which may bring laser ablation. The tumor size and location near organs
results bias. Second, few studies had reported whether and vascular structures were evaluated using computed
this technique was appropriate for metastatic lymph tomography (CT) or magnetic resonance image (MRI) and

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 US. The efficacy of local ablation could be sorted into four Zhuang Deng, Guo Tian, Fen Chen, Haiwei Bao, Ju Li
types of complete response (CR), partial response (PR), 9. Study supervision: Weilin Wang
no change (NC) and lymph node progressive (LP) as the
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