Biomedical Engineering Reference
In-Depth Information
lesion near the treated area, which was completely ablated by sec-
ond HIFU ablation.
HIFU ablation has also been used for palliation in patients
with advanced-stage liver cancer. Li et
al. [108] reported a series
of 100 patients with liver cancer who were treated with HIFU,
including 62 patients with primary liver cancer and 38 with met-
astatic liver cancer. After the treatment, clinical symptoms, such
as loss of appetite, weight loss, and discomfort or pain in the
liver region, were obviously relieved in 87% patients. Compared
to pre-HIFU images, follow-up MRI or CT examinations showed
partial or complete coagulation necrosis of the targeted tumors.
In another study, patients with unresectable HCC received either
HIFU plus supportive treatment (HIFU group,
n
= 151) or sup-
portive treatment only (control group
,
n
= 30), according to their
willingness [109]. A complete or a partial response was achieved
in 28.5% (
n
= 43) or 60.3% (
n
= 91) of cases in the HIFU group.
In contrast, the response rates were 0% and 16.7%, respectively,
in the control group. In addition, the one- and two-year survival
rates were 50.0% and 30.9% in the HIFU group, which were sig-
nificantly higher than those in the control group (both
P
< 0.01).
In Oxford, United Kingdom, Illing et al. [110] reported
interim results of two prospective, nonrandomized HIFU clini-
cal trials for liver cancer in a Western population. Using either
radiological images such as MRI and contrast ultrasound, or
histological examination, the safety and effectiveness of HIFU
were evaluated in the treatment of 22 patients with metastatic
liver cancer. All patients who completed one treatment ses-
sion with HIFU had some evidence of discrete ablation on both
imaging and histology follow-up. These interim results showed
that HIFU ablation resulted in discrete ablation zones of liver
tumors in all evaluable patients (100%). The adverse event pro-
file was favorable when compared to open or minimally invasive
techniques. In the histological study, the predominant charac-
teristic of HIFU-ablated tissue is coagulation necrosis, but heat
fixation is evident in some areas [111]. Heat-fixed cells appear
normal under haematoxylin and eosin staining, indicating that
this is unreliable as an indicator of HIFU-induced cell death. The
radiological study shows time to maximum enhancement maps
and their 3D views in contrast-enhanced MRI can be used as a
noninvasive tool to assess and potentially to quantify the suc-
cess of HIFU ablation [112]. These results reveal that HIFU is
capable of achieving selective ablation of predefined regions of
liver tumor targets, and that MRI evidence of complete ablation
of the target region can be taken to infer histological success.
In Yokohama, Japan, Numata et al.
[113] reported the prelimi-
nary experiences of using both contrast-enhanced 3D ultrasound
imaging and contrast-enhanced CT/MRI for the evaluation of
HIFU effect on 21 HCC lesions. One month after HIFU abla-
tion, contrast-enhanced CT/MRI showed complete ablation in
18 lesions and partial ablation in three lesions. There was a good
correspondence between contrast-enhanced 3-D ultrasound
imaging immediately after HIFU and contrast-enhanced CT/
MRI one month after HIFU. Orsi
et al. [114] treated 17 patients
with 24 liver metastases at difficult locations in Milan, Italy. After
one session of HIFU treatment, PET-CT and/or MDCT at day
one showed complete response in 22/24 liver metastases one day
after HIFU. No side effects were observed during a median of 12
months of follow-up. However, in Seoul, South Korea, Park et al.
[115] reported different results of using HIFU therapy for 13
patients with liver metastasis from colon and stomach cancer.
Complete ablation was observed in eight patients, and partial
ablation in five cases. Among the patients with complete abla-
tion, three patients had no evidence of recurrence, two presented
new foci of disease in the target organ or distant malignancy,
and three underwent local tumor progression during follow-up
period. From October 2006 to December 2008, Ng
et al. [116]
treated 49 patients with unresectable HCC with a curative intent
in Hong Kong, China. The median size of the treated tumors was
2.2 cm ranging from 0.9 to 8 cm, and each patient underwent a
single session of HIFU. The one- and three-year overall survival
rates were 87.7% and 62.4%, respectively. Child-Pugh liver func-
tion grading was the significant prognostic factor influencing
the overall survival rate.
15.7.4 HIFU therapy for Breast Cancer
The first randomized controlled clinical trial was performed by
our group to explore the possibility of HIFU for the treatment of
patients with localized breast cancer in Chongqing, China [117].
In this study, patients were treated with either modified radical
mastectomy (
n
= 25) or HIFU followed by modified radical mas-
tectomy within one to two weeks (
n
= 23). he HIFU-treated area
included the tumor and 1.5-2.0 cm of surrounding normal tis-
sue. Short-term follow-up and pathological and immunohisto-
chemical stains were performed to assess the therapeutic effects
on the tumor and complications of HIFU. Using gross examina-
tion and triphenyltetrazolium chloride (TTC) staining, complete
coagulation necrosis was confirmed in the treated tissue, which
included the tumor and a wide margin of obviously normal
breast tissue surrounding the tumor. Mean values of the larg-
est parallel and perpendicular dimensions, and volume of HIFU
lesions in excised breasts, were significantly larger than those of
the targeted tumors, respectively [118]. Histological examina-
tions showed that HIFU-treated tumor cells underwent typical
characteristics of coagulation necrosis in the peripheral region
of the ablated tumor in all patients. However, in 11 of 23 patients,
hematoxylin and eosin staining showed normal cellular struc-
ture in the central ablated tumor. By using electronic microscopy
and nicotinamide adenine dinucleotide-diaphorase stain, those
who had normal-appearing cancer cells were not viable, indicat-
ing that HIFU could cause the heat fixation of ablated tumor
through thermal effect [119]. Immunohistochemical staining
showed that no expression of proliferating cell nuclear antigen
(PCNA), matrix metalloproteinase-9 (MMP-9), and cell surface
glycoprotein CD44v6 was detected within the treated tumor
cells in the HIFU group, suggesting that the treated tumor cells
lost the abilities of proliferation, invasion, and metastasis. [120].
In a nonrandomized prospective study, we evaluated the long-
term clinical effects of HIFU on patients with breast cancer [121].
Twenty-two patients with biopsy-confirmed breast cancer were
