Hong Kong,China

Introduction

Liver transplantation is the ultimate treatment for patients with hepatocellular carcinoma (HCC) or cirrhosis.However,the shortage of deceased-donor liver grafts deprives many needy patients of a transplant.The uncertain waiting time is an ordeal for every patient on the waiting list.Since HCC is a rapidly progressive tumor,bridging therapy is usually used when waiting time is long.Transarterial chemoembolization (TACE)is notorious for its low efficacy and radiofrequency ablation (RFA) is associated with tumor seeding as well as dense adhesion which poses extra difficulty in the subsequent operation.We hereby report our method of using high-intensity focused ultrasound (HIFU)ablation as a bridging therapy for patients with HCC.

Surgical technique

A 61-year-old man with hepatitis-B-related liver cirrhosis and noted to have an 11×12×11 mm tumor at the dome of the liver by CT scan was referred to us for management in 2006.Blood tests showed that his serum total bilirubin level was 14 μmol/L,serum albumin level 29 g/L,serum α-fetoprotein level 4 ng/mL,platelet count 20×109/L,and international normalized ratio 1.5.His model for end-stage liver disease score was 11.He was put on the liver transplant waiting list,awaiting a cadaveric liver.Multiple sessions of TACE were performed as bridging therapy but his liver function further deteriorated with the presence of gross ascites,and his tumor was found to have doubled in size in May 2010 while he was waiting for transplantation (Fig.1).HIFU ablation was performed in the same month.

The patient was put under general anesthesia and in a right lateral position.HIFU ablation was carried out using the JC HIFU system (Chongqing Haifu Technology,Chongqing,China).The system included a real-time diagnostic imaging unit which provided direct visualization of the tumor,and a therapeutic unit which consisted of an ultrasound energy transducer.The transducer converged ultrasound energy at a 12-cm focal point.Focused ultrasound was produced by the transducer operating at 0.8 MHz.Detailed planning was carried out according to the tumor size and location in the computer monitoring module which was synchronized with the real-time diagnostic imaging probe.Parallel slices of the target tumor with 5-mm separation were planned.Ablation lasted for 2864 seconds.A total of 1122639 J was transferred to the HCC at an average power of 391 W.A satisfactory grey-scale change signifying tumor destruction was observed.No complications occurred after the operation.

Fig.1.Computed tomography scan before HIFU treatment showing a solitary 3-cm lesion at the liver dome with arterial enhancement (lipoid stain inside the lesion) (A) and portovenous washout (B).

Fig.2.Magnetic resonance imaging scan one month after HIFU treatment showing complete radiological ablation of the lesion.T1-weighted hyperintensity (A),T2-weighted hypointensity (B),lack of arterial enhancement (C),and portovenous washout (D).

Blood tests on day 7 showed that his serum total bilirubin level was 16 μmol/L,serum albumin 34 g/L,serum α-fetoprotein 3 ng/mL,platelet count 24×109/L,and international normalized ratio 1.4.Magnetic resonance imaging was performed one month after the HIFU treatment and showed complete ablation of the tumor lesion (Fig.2).

Fig.3.Histology of the liver explant (HE staining,original magnification ×100).Part of the tumor nodule shows coagulative necrosis.Viable tumor cells are identifiable in the left lower quadrant.

Deceased-donor liver transplantation was subsequently performed in November 2010.During the laparotomy,no adhesion was encountered.The diaphragm was intact with ablation injury noted.Pathological examination of the explanted liver showed a 3-cm nodule in the subcapsular region at the dome.The nodule had a yellowish solid cut surface.Grossly necrotic areas were also identified.The entire nodule was embedded for histological examination.Microscopically,coagulative necrosis involved about 80% of the nodule.In these areas,coagulative necrosis and scattered hemosiderin pigment deposits were observed on almost the whole cut surface.Focally viable tumor cell nests were identified at the edge (Fig.3).Computed tomography performed at six months after transplantation showed no recurrence of disease.

Discussion

Liver transplantation is one of the best solutions to HCC and cirrhosis but the shortage of deceased-donor liver grafts,especially in Asia,makes it impossible for everyone in need of this treatment.In 1994,Mazzaferro et al[1]stated that patients with a single lesion ≤5 cm or up to three lesions each measuring ≤3 cm would have optimal transplantation outcomes with the lowest recurrence.Under the selection criteria,patients with tumor progression are removed from the liver transplant waiting list.Bridging therapy is a way to slow down tumor progression to keep a patient on the list,but there are few options for patients with cirrhosis.[2]

TACE and RFA are the most common bridging therapies.Although TACE is generally well tolerated by patients with cirrhosis,it is contraindicated in those with decompensated cirrhosis and ascites.Besides,it is not very effective for larger tumors and disease progression is common.RFA is an effective mode of thermal ablation treatment,but it may not be practical in some cases.[3]It can cause intolerance and major complications in patients with severe cirrhosis.[4]In the present case,the patient was not given TACE or RFA because he had gross ascites,thrombocytopenia,and a difficult tumor location.

HIFU ablation uses a unique frequency of ultrasound waves of 0.8 to 3.5 MHz focused at a distance from the radiating transducer.The accumulated energy at the focused region induces coagulative necrosis of the target lesion by elevating the tissue temperature to above 60 ℃.The temperature outside the focal point remains static as particle oscillation remains minimal.Because ultrasound energy travels much better in water than in air,the presence of ascites actually facilitates energy propagation to the target HCC.[5]

Our center started offering HIFU treatment in 2006 as a non-invasive mode of surgical ablation for patients who could not tolerate liver resection because of poor liver reserve.Subsequently,indications were extended to include patients who had low platelet counts or poor clotting profiles to avoid tumor bleeding that might be caused by direct needle puncture in RFA treatment.Our initial results showed that the complete ablation rate with single ablation was 89.2%.[6]To date,we have performed more than 200 cases of HIFU ablation to treat HCC and no postoperative liver failure has been recorded.There are two contraindications to HIFU treatment:a serum total bilirubin level ＞100 μmol/L and unsuitability for general anesthesia.

HIFU ablation was safely performed in the present case even though the patient had thrombocytopenia.The unique needleless design of the HIFU system makes HIFU ablation superior to RFA,for needle penetration may induce hemorrhage from a hypervascular tumor in a patient with coagulopathy and a low platelet count.Furthermore,without needle puncture,there is no risk of direct tumor seeding to the surrounding major vessels.In the present case,the tumor was located at the dome of the liver,so an open approach would be required if RFA was decided.Last but not least,the absence of adhesion at the surrounding tissue and diaphragm after HIFU treatment is a definite advantage for subsequent surgery because unnecessary dissection and blood loss are prevented and the operation time is shorter.

In conclusion,HIFU ablation is a potentially curative measure which seems to be safe,effective and causing minimal disruption to subsequent laparotomy for HCC patients awaiting liver transplantation.

Contributors:CTT proposed the study.CTT and CKSH wrote the first draft.LRCL and SWW analyzed the data.All authors contributed to the design and interpretation of the study and to further drafts.CSC,PRTP,FST and LCM contributed to thefinal version of the paper.CTT is the guarantor.

Funding:None.

Ethical approval:Not needed.

Competing interest:The authors do not choose to declare any con flict of interest related directly or indirectly to the subject of this article.

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4 Eisele RM,Schumacher G,Jonas S,Neuhaus P.Radiofrequency ablation prior to liver transplantation:focus on complications and on a rare but severe case.Clin Transplant 2008;22:20-28.

5 Wu F.Extracorporeal high intensity focused ultrasound in the treatment of patients with solid malignancy.Minim Invasive Ther Allied Technol 2006;15:26-35.

6 Ng KK,Poon RT,Chan SC,Chok KS,Cheung TT,Tung H,et al.High-intensity focused ultrasound for hepatocellular carcinoma:a single-center experience.Ann Surg 2011;253:981-987.