Jpn J Intervent Radiol Vol.28 No.4 2013

State of the Art
The Current Trend of Treatment for the Virus Hepatitis, and Hepatocellular carcinoma

An Introduction  
Department of Diagnostic Radiology, Kumamoto University Hospital
Osamu Ikeda

1. Management of Chronic Hepatitis

Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University
Motohiko Tanaka, Yutaka Sasaki

Hepatocellular carcinoma (HCC) is strongly associated with chronic liver diseases. Their control is indispensable to suppress hepatocarcinogenesis. Seventy percent or more cases of HCC were based on chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, while the number of cases arising from non-viral liver diseases, especially from non-alcoholic fatty liver disease, is increasing. This goal of therapies for chronic liver diseases is to improve quality of life and survival by preventing progression of the diseases to liver failure, HCC and death. This goal can be achieved if HBV replication can be suppressed in a sustained manner or if HCV can be eradicated. Two different types of drug can be used in the treatment of HBV: interferon and nucleoside/nucleotide analogues. The patients should be considered for treatment when they have HBV DNA levels above 4 log copies/ml and ALT levels above 30 IU/l in chronic hepatitis, and detectable HBV DNA levels in liver cirrhosis. In cases of chronic hepatitis, pegylated interferon or entecavir should be appropriately applied by taking into account viral status, disease severity or age. The cirrhotic patients should be treated with entecavir. On the other hand, the standard-of-care (SOC) for treatment of chronic hepatitis C in difficult-to-treat situations, with genotype 1 infection and high viral load, is triple therapy of telaprevir, pegylated interferon and ribavirin. The sustained viral response rate of naïve case is over 70% with this therapy. Numerous clinical trials using direct acting antivirals are now in progress. All oral, interferon-free therapies will be approved as SOC with greater efficacy and fewer adverse events in the near future.

Key words

  • Interferon
  • Direct acting antiviral therapy
  • Nucleoside/nucleotide analogue

2. Latest Surgical Treatment of Hepatocellular Carcinoma Focusing on“Endoscopic Surgical Treatment”and “Hepatic Resection Combined with IVR”

Department of Multidisciplinary Treatment for Gastroenterological Cancer,
Innovation Center for Translational Research, Kumamoto University Hospital1)
Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University2)
Toru Beppu1,2), Hiromitsu Hayashi2), Hidetoshi Nitta2), Kastunori Imai2)
Daisuke Hashimoto2), Akira Chikamoto2), Takatoshi Ishiko2), Hideo Baba2)

The long-term survival after hepatic resection for hepatocellular carcinoma remains unsatisfactory because of the high incidence of tumor recurrence. Both curability and preservation of liver functional reserve are required. We introduced in this paper following: 1) advances in hepatic resection, 2) less invasive endoscopic surgical treatments consisting of endoscopic hepatic resection and endoscopic ablation therapy, 3) hepatic resection followed by adjuvant hepatic arterial infusion chemotherapy for hepatocellular carcinoma patients with vascular invasion, and additional effects of portal vein embolization on hemi-hepatectomy. We believe that this subject might encouraging radiologists to collaborate with surgeons for the purpose of further improvement of hepatocellular carcinoma treatment results.

Key words

  • Hepatocellular carcinoma
  • Endoscopic surgical treatment
  • Hepatic resection combined with IVR

3. Liver Transplantation for Hepatocellular Carcinoma

Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Science
and Transplant Medicine1), Kumamoto University
Takayuki Takeichi, Katsuhiro Asonuma1)

Liver transplantation (LT) is the only treatment for end-stage liver disease. In Japan, the focus is on living donor liver transplantation (LDLT) because of the small number of deceased donor liver transplants resulting from the low cadaveric organ donation rate. Hepatocellular carcinoma (HCC) is a good indication for LT, because LT removes the cancer and eradicates the cirrhosis in HCC patients selected to undergo LT and has achieved the best outcomes. The Milan criteria have been accepted as the gold standard for the selection of HCC patients for LT worldwide. In 2004, the health insurance program in Japan began to cover LT for candidates meeting the Milan criteria. In Japan, patient survival after LDLT for HCC is good compared with that for other diseases. Recently, several groups have proposed new extended criteria for LT beyond the Milan criteria. We expect that these new extended best criteria will not incur an increased recurrence rate or a decreased patient survival rate in Japan.

Key words

  • Liver transplantation
  • Living donor liver transplantation
  • Hepatocellular carcinoma
  • Milan criteria

4. Sorafenib for Hepatocellular Carcinoma

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East
Masafumi Ikeda, Shuichi Mitsunaga, Satoshi Shimizu, Izumi Ohno
Hideaki Takahashi, Hiroyuki Okuyama, Akiko Kuwahara
Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital
Takuji Okusaka

In two pivotal international phase 3 trials of sorafenib vs. placebo, sorafenib, which is a multikinase inhibitor of Raf kinase, vascular endothelial growth factor receptor-2/-3 (VEGFR-2/-3) and platelet-derived growth factor receptor beta (PDGFR-β), was found to prolong the overall survival and time to progression in patients with advanced hepatocellular carcinoma (HCC). After the introduction of sorafenib in Japan, it has been widely used for the treatment of patients with advanced HCC. The definitive indications of sorafenib in patients with HCC are considered to be the presence of extrahepatic metastasis, macrovascular invasion, and refractoriness to TACE. On the other hand, sorafenib has some troublesome adverse effects, such as the hand-foot syndrome, hypertension, and liver dysfunction. Therefore, it is important in clinical practice to clearly identify good candidates for treatment with sorafenib and to be aware of the proper management of the adverse events of the drug. Various novel systemic chemotherapeutic agents and combined regimens including sorafenib are currently under development as adjuvant therapies after resection or local ablative therapy, for use in combination with transcatheter arterial chemoembolization, as first-line chemotherapies for advanced HCC, or for use in the second-line setting after sorafenib therapy. In the future, further improvements in the treatment outcomes of HCC are expected.

Key words

  • Hepatocellular carcinoma
  • Sorafenib
  • Molecularly targeted agent

5. Radiofrequency Ablation for Hepatocellular Carcinoma

Division of Interventional Radiology, Shizuoka Cancer Center
Takeshi Aramaki, Michihisa Moriguchi, Emima Bekku

Radiofrequency ablation (RFA) is a key treatment option for hepatocellular carcinoma (HCC) and was developed in 1995. RFA is suitable for early-stage HCC (≤3 lesions ≤3 cm in diameter; Child-Pugh score A or B according to the Japanese clinical guidelines for liver cancer; usually indicated for platelets ≥50,000mm3; absence of ascites). Indications for RFA are usually decided based on computed tomography, ultrasonography (US) and magnetic resonance imaging (MRI) and contrast medium is necessary for evaluation. RFA is usually performed under ultrasonographic guidance, and CT guidance is sometimes useful to treat the lesion, which is difficult to detect on US. Artificial ascites and/or hydrothorax are useful to detect lesions located at the dome of the liver and to protect against injury to the lung, gastrointestinal tract and so on. Treatment effects are usually evaluated using CT, and Gd-EOB-DTPA-MRI is also useful for accurate evaluation of treatment margins in RFA. Phase III clinical trials of sorafenib and peretinoin are now ongoing as adjuvant therapies after RFA.

Key words

  • Hepatocellular carcinoma
  • Radiofrequency ablation
  • Image guidance

6. TACE for Hepatocellular Carcinoma

1)Conventional TACE

Department of Radiology, Nara Medical University
Hiroshi Anai, Toshihiro Tanaka, Hideyuki Nishiofuku, Kimihiko Kichikawa

Transcatheter arterial chemoembolization (TACE) has been widely introduced for inoperable hepatocellular carcinoma (HCC) since the 1980s. The procedure and maneuvers such as diagnostic imaging, microcatheters and microguidewires have been also become more sophisticated, allowing selective TACE to be performed even for small HCCs with good results and safety. TACE has been performed using Lipiodol emulsion mixed with anticancer agents and gelatin sponge particles via the feeding arteries as selectively as possible. However the current treatment algorithm and/or guidelines have stated surgical treatment and local ablation treatment as curative treatments for early HCC due to their good local control. Many drugs have been developed and distributed for hepatitis or hepatic viruses, despite which many HCC patients still suffer recurrence. So TACE still plays a very important role in the treatment course of each HCC patient. We need to keep the development and innovation of conventional TACE much more. We will review the current conventional TACE and describe its future prospects.

Key words

  • Hepatocellular carcinoma
  • Lipiodol-TACE
  • Segmental Lip-TACE

6. TACE for Hepatocellular Carcinoma

2)Spherical Embolic Agents for Liver Tumor Embolization

Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine
Keigo Osuga, Noboru Maeda, Hiroki Higashihara, Kaishu Tanaka
Kentaro Kishimoto, Masahisa Nakamura, Yusuke Ono, Noriyuki Tomiyama
Department of Diagnostic Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases
Tetsuro Nakazawa

Recently, three products of calibrated microspheres (Embosphere®, HepaSphere®, and DC-Bead®) have been approved in Japan as embolic agents for hypervascular tumors and arteriovenous malformations. The advantages of these microspheres are that the particles are uniform in size, and easy to inject through a microcatheter. They can travel distally to vessels corresponding to the particle size, and thus, the occlusion level is predictable. Worldwide, the use of these microspheres has been already prevalent in chemoembolization or bland embolization of hepatocellular carcinoma. Two of the approved microspheres (DC-Bead® and HepaSphere®) are also applied as drug-eluting microspheres. However, operators should pay attention to some pitfalls in the use of microspheres. Temporary aggregation and redistribution of microspheres may restore the blood flow of a once occluded vessel. The mechanical properties of drug eluting microspheres may alter upon drug loading and release. Therefore, we need to understand the behavior of each microsphere to obtain the optimal embolic effects. It is also important to investigate the true benefits of microspheres or in what clinical or pathological conditions they will improve the safety and efficacy compared to conventional materials.

Key words

  • Microspheres
  • Embolization
  • Chemoembolization

6. TACE for Hepatocellular Carcinoma

3)Balloon-occluded Trans-arterial Chemoembolization (B-TACE): Comparison with Ultra-selective TACE (U-TACE)

Department of Radiology, Hitachi General Hospital
Toshiyuki Irie, Masashi Kuramochi
Department of Diagnostic Radiology, Tsukuba Memorial Hospital
Nobuyuki Takahashi

Balloon-occluded trans-arterial chemoembolization (B-TACE) achieves high accumulation of lipiodol in hepatocellular carcinoma (HCC) nodules and enables forceful retrograde injection of embolization materials into the collateral vessels, which improves local control of HCC nodules. Ultra-selective TACE (U-TACE) is also known to improve local control of HCC nodules. We consider the reason why U-TACE improves local control to also be forceful injection of embolization materials. In this paper, we discuss the mechanism of B-TACE and U-TACE, and disclose the know-how of B-TACE.

Key words

  • Balloon-occluded TACE
  • Ultra-selective TACE
  • Hepatocellular carcinoma

Case Reports

Superior Mesenteric Artery Thrombosis Developing during the Course of Diabetic Ketoacidosis Treated by Thrombolytic Therapy: A Case Report

Department of Emergency and Critical Care Medicine and Radiology1),
Yokohama City Minato Red Cross Hospital
Tetsuya Takahashi, Toshitaka Ito, Hideho Endo1)
Michiko Fujisawa, Tetsuhiro Takei, Keiichi Yagi

The patient was a woman in her 40s with type I diabetes mellitus, who presented with the chief complaint of consciousness disturbance. Findings at the first visit: GCS E3V2M5; no abnormal findings on physical examination or plain CT of the abdomen. The patient was diagnosed as having diabetic ketoacidosis (DKA) based on the following laboratory findings: blood glucose level, 1028 mg/dl; Base Excess (BE), -28.4 mmol/l. By 10 hours after hospitalization, the blood glucose level had decreased to 150 mg/dl and the patient became alert, however, the BE remained at -12.5 mmol/l. At 11 hours after admission, the patient began to complain of abdominal pain. A contrast-enhanced CT of the abdomen showed poor visualization of almost the entire small intestine. On angiography, occlusion of the superior mesenteric artery (SMA) was recognized, while the middle and right colic artery and some portions of the jejunal arteries could be visualized. As the family declined to provide consent for surgery, thrombolytic therapy was administered. While the thrombus in the SMA itself disintegrated, most of the jejunal and ileal arteries remained occluded, and the patient died at 41 hours after hospitalization. Since patients with DKA are at an increased risk of developing intraarterial thrombosis, early diagnosis and prompt treatment are extremely important in those with treatment-resistant abdominal pain and acidosis during the treatment, based on the possibility of intestinal ischemia.

  • Diabetic ketoacidosis
  • Superior mesenteric artery
  • Interventional radiology

Case Reports

A Case of EVAR for Mycotic Abdominal Aortic Aneurysm

Department of General Medicine, Radiology1), Therapeutic Radiology2)
and Cardiovascular Surgery3), Kochi Health Sciences Center
Kensuke Uraguchi, Yoshihiro Noda1), Kazuko Murata1), Satoshi Matsusaka1)
Yuka Tokuhiro2), Yasuhiro Hata2), Sojiro Morita2)
Satofumi Tanaka3), Kensuke Ohue3), Manabu Okabe3)
Department of Radiology, Mie University
Noriyuki Kato

Mycotic aortic aneurysms are rare, with a reported incidence of 1-1.8% of all aortic aneurysms. We report a case of endovascular aneurysm repair (EVAR) for a mycotic abdominal aortic aneurysm.
An 80-year-old woman with knee pain was found to have an aortic aneurism on magnetic resonance imaging scan of the lumbar spine. Hematologic test results indicated markedly elevated levels of inflammatory enzymes, and mycotic abdominal aortic aneurysm was diagnosed.
Initially, antibiotic treatment and EVAR was planned, after improvement in the patient's inflammatory response. However, on the third day after hospitalization, contrast-enhanced computed tomography (CT) showed an enlarged aneurysm. Therefore, an emergency EVAR was performed because of rupture. Seventy-six days postoperatively, that is, the period from the operation to discharge, no complications were noted. One year after the discharge, the follow-up CT scan indicated a stable and reduced aneurysm.

Key words

  • Mycotic aortic aneurysm
  • EVAR

Case Reports

A Case of Advanced Hepatocellular Carcinoma Invading the Inferior Vena Cava (IVC), which was Successfully Treated with IVC Stent

Department of Radiology, Hirosaki University Hospital
Toshihide Tokuda, Shuichi Ono, Hiromasa Fujita, Akihisa Kakuta, Shinya Kakehata
Fumiyasu Tsushima, Koichi Sibutani, Hiroyuki Miura, Yoshihiro Takai
Department of Radiology, Aomori Rousai Hospital
Isao Ikami

Advanced malignant liver tumors often invade the intrahepatic inferior vena cava (IVC). This can result in its obstruction, possibly causing IVC syndrome. Symptoms of IVC include leg edema and ascites, which in turn can result in an impaired quality of life. Accordingly, palliative treatment is needed to improve the condition of such patients. However, these symptoms often respond poorly to diuretics, leading to rapid deterioration of edema, which may become intractable. Therefore, this situation is considered an “Oncologic Emergency.”
Stenting and radiation therapy have been reported as treatment for advanced malignant liver tumors with IVC syndrome.
Recently, we encountered a case of hepatocellular carcinoma with IVC invasion and IVC syndrome, which was successfully treated with stenting. Here, we present and discuss this case and review the relevant literature.

Key words

  • Inferior vena cava (IVC) syndrome
  • IVC stent
  • Hepatocellular carcinoma (HCC)

Case Reports

Removal of a Fractured Guidewire in a Liver Abscess Cavity Using Biopsy Forceps: A Case Report

Departments of Radiology and Surgery1), Saiseikai Utsunomiya Hospital
Koki Kato, Masanori Honda, Keiichi Tanimura
Toshiaki Yagami, Nobuyoshi Nishizawa1), Hiroharu Shinozaki1)

Arare case of retrieval of a fractured guidewire in a liver abscess cavity through a percutaneous transhepatic route using biopsy forceps is reported. A woman in her 70s was admitted to our hospital with high fever and fatigue. Abdominal CT revealed abscesses in the left lobe of the liver, and percutaneous drainage was performed the next day. However, after two weeks of drainage and antibiotic therapy, the symptoms and abscesses were not much improved. During tract dilatation to insert a larger drainage tube, the soft tip of the stainless steel guidewire fractured and fell into the liver abscess cavity. After the accident, removal of the fractured guidewire was attempted. Endoscopic biopsy forceps were inserted through the percutaneous transhepatic drainage route, and the fractured guidewire was successfully removed under fluoroscopic guidance. After retrieval of the fractured guidewire and additional drainage, the patient became afebrile, and CT demonstrated that the abscess had disappeared.

Key words

  • Forceps
  • Guidewire
  • Liver abscess
  • Retrieval

Co-medical Corner

Evaluation of the Enhancement Effect in the Intracranial Imaging Using Iso-osmolar Contrast Media

Department of Radiological Technology and Neurosurgery2), Nagoya University Hospital
Department of Radiological Technology, Nagoya University School of Health Sciences1)
Takuya Nishimoto, Kuniharu Imai1), Masaki Mori Michiko Hata, Shigeru Miyachi2), Kazuo Yoneda

Key words : Iso-osmolar contrast media, Angiography, Evaluation of the Enhancement effect