Iodine-125 seed implantation for synchronous
pancreatic metastases from hepatocellular
A case report and literature review
Junjie Xiong, MD
, Selina Kwong Chian, MBBS
, Jiao Li, BN
, Xubao Liu, MD PhD
Rationale: The image-guided iodine-125 seed implantation has been widely used for a variety of tumors, including prostatic
cancer, pulmonary cancer, hepatocellular carcinoma and pancreatic cancer. However, the clinical value of iodine-125 seed
implantation for the treatment of pancreatic metastasis from hepatocellular carcinoma has not been reported. We presented the ﬁrst
case with ultrasound-guided iodine-125 seed implantation for this disease.
Patient concerns: We presented the case of a 48-year-old man patient with primary hepatocellular carcinoma and pancreatic
metastasis who was managed with ultrasound-guided iodine-125 seeds implantation.
Diagnoses: She was diagnosed with synchronous pancreatic metastases from hepatocellular carcinoma.
Interventions: Puncture biopsy and ultrasound-guided iodine-125 seeds implantation.
Outcomes: The hepatic and pancreatic tumors were obviously reduced after 15 months. Moreover, the liver function test was
mildly abnormal in glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase.
Lessons: The image-guided iodine-125 seeds implantation was an important therapeutic approache to unresectable hepatocellular
carcinoma with pancreatic metastasis. However, more related cases should be reported for further evaluating the value of the way.
Abbreviations: AFP =alpha-fetoprotein, ALB =albumin, ALT =glutamic-pyruvic transaminase, APTT =activated partial
thromboplastin time, AST =glutamic-oxalacetic transaminase, CA19-9 =carbohydrate antigen 19-9, CEA =carcinoembryonic
antigen, CT =computerized tomographic scanning, GGT =glutamyl transpeptidase, GPC3 =glypican 3, HbcAB =hepatitis B core
antibody, HbeAg =hepatitis B e antigen, HbsAg =hepatitis B surface antigen, HBV-DNA =hepatitis B virus deoxyribonucleic acid,
HCC =hepatocellular carcinoma, HCV =hepatitis C virus, HE =hematoxylin-eosin, HGB =hemoglobin, INR =International
Normalized Ratio, NEUT =neutrophil, PD =prescription dose, PLT =blood platelet, WBC =white blood cell, PT =prothrombin time,
PV =portal vein, RFA =radiofrequency ablation, SMA =superior mesenteric artery, SV =splenic vein, TACE =transcatheter arterial
Keywords: hepatocellular carcinoma, iodine-125, metastasis, pancreas
Hepatocellular carcinoma (HCC) is one of the most common
malignant tumors in the world. Among primary liver cancers,
HCC is the major histological subtype and ranks fourth among
the organ-speciﬁc causes of cancer related deaths worldwide.
Extrahepatic metastases are commonly found during the
diagnosis of HCC. The most common sites of extrahepatic
metastatic HCC are the lungs, lymph nodes, bones, and adrenal
However, metastasis to the pancreas
occurs in only <1% of patients with HCC.
guided iodine-125 seed implantation can achieve a necrotizing
dose of irradiation within the target volumes with a very sharp
falloff outside the implanted area, thus sparing the normal tissues
around the lesion. It has been widely used for a variety of tumors,
including prostatic cancer,
However, the clinical value of iodine-125
seed implantation for the treatment of pancreatic metastasis of
HCC has not been reported. To the best of our knowledge, this is
the ﬁrst report of iodine-125 seed implantation as the treatment
of pancreatic metastasis from HCC. Using our experience, a
world literature review of all such cases was performed in order
to better recognize this rare pathology.
2. Case presentation
A 48-year-old man was admitted to West China Hospital of
Sichuan University as result of abdominal pain in the right upper
quadrant. He suffered from hypertension for 1 year and was
Authors’contributions: XJ drafted the manuscript, and contributed to acquisition
of material; XJ and LJ collected material and patient’s information; LX revised the
manuscript and reviewed the literature; KCS revised the manuscript and modiﬁed
the language. All authors read and approved the ﬁnal manuscript.
The authors have no conﬂicts of interest to disclose.
Department of Pancreatic Surgery,
West China School of Medicine,
Department of Emergency, West China Hospital, Sichuan University, Chengdu,
Sichuan Province, China.
Correspondence: Xubao Liu, Department of Pancreatic Surgery, West China
Hospital, Sichuan University, Guo Xue Rd 37, Chengdu, Sichuan, 610041, China
Copyright ©2017 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the terms of the Creative
Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-
ND), where it is permissible to download and share the work provided it is
properly cited. The work cannot be changed in any way or used commercially
without permission from the journal.
Medicine (2017) 96:46(e8726)
Received: 8 October 2017 / Received in ﬁnal form: 20 October 2017 / Accepted:
23 October 2017
Clinical Case Report Medicine®
given oral medication. There was no remarkable family history.
On admission, the vital signs of the patients were within the
normal limits. On physical examination, the abdomen was soft,
but tender in the right upper quadrant. The blood examination
showed the following: hemoglobin (HGB) was 149 g/L (reference
range: 135–175 g/L), blood platelet (PLT) was 134 10
(reference range: 100–300 10
/L), white blood cell (WBC)
was 4.99 10
/L (reference range: 3.5–9.5 10
of neutrophil (NEUT) was 62.6% (reference range: 40–75%).
The prothrombin time (PT) was 14.0 seconds (reference range:
9.6–12.8 seconds), activated partial thromboplastin time (APTT)
was 28.1 seconds (reference range: 20–40 seconds), international
normalized ratio (INR) was 1.24 seconds (reference range: 0.86–
1.14seconds). The patient’s liver function tests showed the
albumin (ALB) was 36.6 g/L (reference range: 40–55 g/L), A/G
was 1.12 (reference range: 1.2–2.4), and glutamyl transpeptidase
(GGT) was 176 IU/L (reference range: <60IU/L). The hepatitis
serology was positive including hepatitis B surface antigen
(HbsAg), hepatitis B e antigen (HbeAg), and hepatitis B core
antibody (HbcAB). Hepatitis B virus deoxyribonucleic acid
(HBV-DNA) was 1.31E+05 copies/mL (reference range: <1.00E
+03 copies/mL). Tumor marker assays showed raised alpha-
fetoprotein (AFP) with 96.43 ng/mL (reference range: <8 ng/mL)
and carbohydrate antigen 19–9 (CA 19–9) with 34.54 IU/mL
(reference range: <22 IU/mL). However, carcinoembryonic
antigen (CEA) was 1.93 ng/mL (reference range: <5 ng/mL).
Furthermore, the abdominal enhanced computerized tomograph-
ic scanning (CT) scans found that there was a 4 3 cm mass in the
head of the pancreas (Fig. 1A). However, the imaging specialist
suspected the presence of a tumor in the left lobe of the cirrhosis
liver (Fig. 1B) which was conﬁrmed by subsequent intraoperative
exploration. The chest x-ray scan was normal.
When all the preoperative examinations were completed, the
patient underwent exploratory laparotomy. We found a mass of
about 4 4 cm in the nodular cirrhosis liver, which was located in
segment IV, and a mass of about 4 3 cm in the pancreatic head.
The pancreatic neoplasm had broken through the capsule of the
pancreas, and invaded the superior mesenteric artery (SMA),
portal vein (PV), and splenic vein (SV). However, the main
pancreatic duct had no dilatation, and the duodenum had neither
invasion nor stricture. Therefore, primary pancreatic cancer with
hepatic metastasis was suspected. We conducted the puncture,
with 18-gauge needles, for hepatic and pancreatic masses under
ultrasonic guidance for frozen section. After that, considering the
liver cirrhosis and the patient’s condition, ultrasound-guided
iodine-125 seeds were implanted into the hepatic and pancreatic
tumors. The ethics committee of West China hospital approved
this study and the patient signed the informed consent form.
The iodine-125 seeds were provided by the Beijing ZHIBO
BioMedical Technology Company, China. Each particle was 0.8
mm in diameter and 4.5mm in length, with a radioactivity of 0.6
to 0.8 mCi, radioactive half-life of 60.2 days, and radiation
energy of 28 keV. Pre-procedural planning was conducted.
Tumor volume was measured during laparotomy by intra-
operative ultrasonography. The procedure for iodine-125 seed
implantation was carried out under the guidance of ultrasound.
18-gauge needles were inserted into the tumor mass at intervals of
1.0 cm in a parallel array, extending at least 0.5 to 1.0cm beyond
Figure 1. CT scan suggested a heterogeneous enhanced mass in the pancreatic head (A: white arrow) and an unobvious mass in the left of the liver (B: white
arrow). C T =computerized tomographic scanning.
Figure 2. Hematoxylin and eosin stains showed poorly differentiated malignant cells in the hepatic (A) and pancreatic masses (B) (400).
Xiong et al. Medicine (2017) 96:46 Medicine
the margins of pancreatic lesions. Penetration of the pancreatic
duct, small blood vessels, and adjacent transverse colon was
avoided. After the needles were placed, iodine-125 seeds were
implanted using a Mick applicator and the spacing was
maintained at 1.0 cm intervals. The prescription dose (PD) was
set to 140 Gy.
The postoperative hematoxylin-eosin (HE) staining suggested
that the hepatic tumor was poorly differentiated HCC, and
the pancreatic tumor was a metastasis of the HCC (Fig. 2). The
above diagnosis was further supported by immunohistochemical
staining. The immunocytochemical panel consisted of HepPar1,
glypican 3 (GPC3), AFP, CK8, CK18, CK7, and CK19. Of these,
the hepatic neoplastic cells were strongly and diffusely positive
for HepPar1, GPC3, CK8, and CK18 (Fig. 3). All other
immunocytochemical stains were negative. In comparison, the
GPC3, CK8, CK18, and CK19 were positive in the pancreatic
neoplastic cells. The ﬁnal diagnosis was pancreatic metastatic
tumor from HCC. The patient’s immediate postoperative course
was uneventful. A medical oncologist did not recommend
adjuvant systemic chemotherapy. After the operation, the patient
was followed up with routine CT scans performed every 3
months. Based on this, 15 months after the initial operation of the
patient, the CT examination suggested that the tumor size of the
hepatic and pancreatic tumors were obviously reduced (Fig. 4).
Moreover, the liver function test was mildly abnormal except for
only a slight elevation in glutamic-oxalacetic transaminase (AST,
65IU/L) and glutamic-pyruvic transaminase (ALT, 60 IU/L).
HCC is one of the most common and fatal cancers in the world.
It is a disease that is much more common in the Eastern world. In
China, most of the patients have underlying cirrhosis associated
with HBV or hepatitis C virus (HCV) viral hepatitis. Currently,
the symptoms of metastases conﬁned to the pancreas at the time
of diagnosis are diagnostically unspeciﬁc, and imaging also rarely
Figure 3. Immunohistochemical stains showing positive staining of the tumor cells for HepPar1 (A), GPC3 (B), and CK8 (C) (400).
Figure 4. CT images at 15 months after I-125 seed implantation suggested that the tumors were largely reduced (A: hepatic tumor [white arrow], B: pancreatic
tumor [white arrow]). CT =computerized tomographic scanning
Literature review for pancreatic metastasis from HCC.
Author Year Country Tumor location Diagnostic method Therapy Survival
Lowe 1997 USA Pancreatic head FNA Palliative surgery (Roux-en-y
Texler 1998 Australia Pancreatic tail Postoperative pathological
Surgical excision (hepatectomy,
distal pancreatectomy, splenectomy)
More than 16 months
Sugai 1999 Japan Pancreatic tail FNA TACE (HCC) and PEI (pancreatic metastasis) Unknown
Thirabanjasak 2009 Thailand Pancreatic body FNA Chemotherapy More than 9 months
FNA =ﬁne needle aspiration, HCC=hepatocellular carcinoma, PEI =percutaneous ethanol injection, TACE=transcatheter arterial chemoembolizatio n.
Xiong et al. Medicine (2017) 96:46 www.md-journal.com
shows abnormalities seen only in primary neoplasms. In our
patient, the metastatic pancreatic tumor originating from the
HCC was a solitary tumor located in the pancreatic head.
However, the primary HCC was not clearly seen in the
preoperative CT. Therefore, pancreatic non-functioning neuro-
endocrine tumors with liver metastasis were also suspected.
Finally, the laparotomy was performed.
Although remote metastasis of HCC accounts for two-thirds of
cases, metastatic HCC to the pancreas is distinctly rare. Only 4
have reported synchronous pancreatic metastases
from the HCC as a literature review (Table 1). However, only this
case was treated with iodine-125 seed implantation. Previously,
HCC had been conﬁrmed to be a radiosensitive tumor. With the
development of new radiotherapy technology and facilities, the
iodine-125 seed implantation therapy has provoked more interest
throughout the world. The iodine-125 seed implantation is an
ideal technique that combines the ability to target tumor cells
under direct visualization and spare uninvolved liver parenchyma
due to the sharp dose falloff outside of the implanted volume.
Moreover, because of the liver’s natural regenerative capabilities,
a high dose of radiation can be delivered to restricted volumes by
brachytherapy. With the property of local conformal radiother-
apy, normal liver is spared. Hence, a potentially tumoricidal dose
of radiation can be administered with acceptable complications.
In 2009, Lv et al
reported that for patients with unresectable
HCC, 48 patients who had failed transcatheter arterial chemo-
embolization (TACE) underwent iodine-125 seed implantation.
The patients’survival rates at 1, 2, and 3 years were 75%, 45.8%,
and 27.1%, respectively, with a median survival time of 15.5
months. The complications were acceptable and could be
managed with conservative treatment. One randomized con-
trolled trial study
suggested that iodine-125 seed implantation
plus radiofrequency ablation (RFA) could obtain better local and
intrahepatic tumor control as well as better long-term survival
compared with treatment with RFA alone. Furthermore, for
advanced tumors, Zhang et al
showed that CT-guided iodine-
125 implantation may be a safe and effective treatment option for
HCC patients with multiple pulmonary metastases. Their results
suggested that the rate of complete response and partial response
were 14.8% and 55.56%, respectively. The survival rates at 1
and 2 years were 67.0% and 30.8%, respectively, with a median
survival of 13.5 months. However, to our knowledge, this is the
ﬁrst case of pancreatic metastases of HCC treated with ultrasonic
guidance iodine-125 seed implantation. At 15 months follow-up,
the tumor size of the hepatic and pancreatic metastasis was
largely reduced. No complications occurred except for mild
abnormal liver function. The iodine-125 seed implantation has
some advantages, such as high-dosage in targeted organs,
minimal damage to normal tissue, and avoidance of organ
motion. It is a minimally invasive and accurate treatment method.
Therefore, image-guided iodine-125 seed implantation may be
a safe and effective treatment option for HCC patients with
In conclusion, this is the ﬁrst report with iodine-125 seed
implantation for the treatment of pancreatic metastasis from
HCC. Although there is presently no consensus on the optimal
treatment strategy for this rare disease, image-guided iodine-125
seed implantation has been regarded as an important therapeutic
approach to unresectable HCC or pancreatic tumor. For this
patient, ultrasound-guided iodine-125 implantation provided an
appropriate strategy for the patient with unresectable HCC
accompanied with pancreatic metastasis, and can be considered
by other hepatopancreatobiliary teams.
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