Purpose: We present results of patients with hepatocellular carcinoma (HCC) treated with proton beam therapy.
Experimental Design: We reviewed 162 patients having 192 HCCs treated from November 1985 ...to July 1998 by proton beam therapy with or without transarterial
embolization and percutaneous ethanol injection. The patients in the present series were considered unsuitable for surgery
for various reasons, including hepatic dysfunction, multiple tumors, recurrence after surgical resection, and concomitant
illnesses. The median total dose of proton irradiation was 72 Gy in 16 fractions over 29 days.
Results: The overall survival rate for all of the 162 patients was 23.5% at 5 years. The local control rate at 5 years was 86.9% for
all 192 tumors among the 162 patients. The degree of impairment of hepatic functions attributable to coexisting liver cirrhosis
and the number of tumors in the liver significantly affected patient survival. For 50 patients having least impaired hepatic
functions and a solitary tumor, the survival rate at 5 years was 53.5%. The patients had very few acute reactions to treatments
and a few late sequelae during and after the treatments.
Conclusions: Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment
mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient
feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic functions, and coexisting intercurrent
diseases.
Aim
Proton beam therapy is safe and more effective than conventional radiation therapy for the local control of nodular hepatocellular carcinoma (HCC). However, evaluating therapeutic response by ...imaging is not accurate during the early post‐irradiation period. Therefore, we examined whether the histopathological study of biopsy specimens obtained at 3 weeks after irradiation can be used to more accurately assess therapeutic response.
Methods
Fifteen HCC lesions from 13 patients were treated with proton beam irradiation. Tissue biopsy samples were obtained using abdominal ultrasound‐guided percutaneous fine‐needle aspiration from the center of the tumor before, 3 weeks after and 1 year post‐proton therapy. The specimens were examined after staining with hematoxylin–eosin (HE) and a MIB‐1 antibody.
Results
MIB‐1 labeling indices (LI) before treatment were 13.0 ± 8.5% (mean ± SD; range, 0.6–27.0), whereas those 3 weeks after proton therapy were significantly reduced to 3.2 ± 2.4% (range, 0.6–8.9) (P < 0.05). Although the tumor size was reduced, we did not observe a reduction in tumor blood flow by dynamic computed tomography or degenerative changes by HE. All lesions that displayed reduced MIB‐1 LI at 3 weeks post‐proton treatment were ultimately diagnosed as complete response at 1 year after treatment. In contrast, one case with increased MIB‐1 LI at 3 weeks had significant tumor size progression at 1 year post‐treatment.
Conclusion
The percutaneous fine‐needle aspiration biopsy of HCC is a safe and useful tool that can be used to evaluate the response to proton irradiation. In particular, MIB‐1 LI may provide additional information to assess the therapeutic response of HCC during the early post‐irradiated period.
We have reported that proton radiotherapy for hepatocellular carcinoma (HCC) is a safe and effective therapeutic option. However, it is difficult to evaluate its effect in certain cases. Recently, it ...has been reported that the usage of contrast-enhanced color Doppler ultrasonography (CECDU) can improve diagnostic accuracy, both in terms of the presence of hepatic tumor and in the evaluation of treatment. The aim of this study was to determine the usefulness of CECDU in assessing the therapeutic response of HCC treated with proton radiotherapy.
Twenty-two patients treated with the proton radiotherapy were studied. We inspected HCC lesions by CECDU, before and after the irradiation, over time. The magnitude of blood flow in the HCC was quantified on still images by CECDU. The ratio of the number of color pixels against that of the total number of pixels in the tumor area was defined as the tumor blood flow ratio (TBFR).
Immediately after the proton treatment, a transient increase of blood flow in the tumor was recognized in more than half of the patients, while the TBFR was unchanged or decreased in the remaining patients. At longer periods after irradiation, the TBFR in all HCCs gradually decreased, and this reduction of TBFR was statistically significant from 9 months after irradiation. These findings are consistent with those obtained previously by computed tomography (CT) as well as magnetic resonance imaging (MRI).
We propose CECDU as a useful diagnostic option for the evaluation of HCC treated with proton radiotherapy.
To elucidate the risk factors for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related liver cirrhosis (LC), we examined 204 cirrhotic patients negative for hepatitis B surface antigen ...and positive for HCV antibodies. The independent influence of various clinical characteristics in these patients was analyzed by multiple logistic regression, and the risk factors for HCC were identified. Multiple logistic regression analysis identified and ranked the following four risk factors: male sex (P < 0.001), habitual heavy drinking (P < 0.005), hepatitis B virus antibody positivity (anti-HBs and/or anti-HBc, P < 0.05), and age greater than 60 years (P < 0.05). The odds ratio of HCC was 4.20 (95% confidence interval; CI, 1.80-9.78) in male patients, 3.27 (95% CI, 1.46-7.30) in habitual heavy drinkers, 2.01 (95% CI, 1.01-3.99) in patients positive for hepatitis B virus antibodies, and 2.06 (95% CI, 1.00-4.23) in patients older than 60 years. The cumulative occurrence rates of HCC after blood transfusion were significantly higher in habitual heavy drinkers (4.8%, 49.4%, and 74.7% at 10, 20, and 30 years, respectively) than in non-drinkers (0%, 21.0%, and 23.3% at 10, 20, and 30 years, respectively, P < 0.0003). The mean interval for progression to LC after blood transfusion was significantly shorter in the habitual heavy drinkers than in the non-drinkers (22.4 +/- 4.4 years vs 28.4 +/- 3.9 years; P < 0.0003). This multivariate analysis revealed that habitual heavy drinking and hepatitis B virus antibody positivity are significant risk factors for HCC in HCV-related liver cirrhosis.
A rare case of severe acute hepatitis A complicated by pure red cell aplasia (PRCA) is reported. A 60-year-old man with jaundice and hepatomegaly was diagnosed as having acute hepatitis A by positive ...IgM anti-hepatitis A antibody (anti-HAV). Severe anemia rapidly developed 3 weeks after admission, and the patient was diagnosed with PRCA by both bone marrow smears and erythrocyte survival study. The anemia was transient and bone marrow recovered within 1 week. However, concomitant with bone marrow recovery, the hepatitis worsened. He became drowsy and disoriented and severe jaundice, ascites, prolonged prothrombin time, increased transaminase levels, and abnormal electroencephalogram (EEG) were exhibited. Plasma exchange transfusion and glucagon-insulin (GI) therapy improved the consciousness level, but bilirubin, transaminase levels, and IgM anti-HAV titer remained high. Intravenous administration of lipophilized prostaglandin E1 (lipo-PGE1) was added to the GI therapy. Bilirubin and transaminase levels were normalized in the 8th week after the initiation of this combination therapy (17 weeks after admission). The combined use of lipo-PGE1 with plasma exchange and GI therapy appeared to be useful for the prolonged severe hepatitis in this patient.
We measured the beam intensity of highly charged argon and krypton ions covering the inner wall of a plasma chamber with an aluminum tube. The beam intensity was enhanced strongly and gas mixing was ...found to be unnecessary.
We successfully produced the intense beam of highly charged Kr
ions using an electrode. Under the pulsed mode operation, we found
that the depth of the plasma potential dip strongly depends on the
...duration of the microwave and takes about 40 ms to reach the
equilibrium state. Taking these results into account, we compared the
beam intensities of highly charged Kr ions with and without the use of
an electrode under the pulsed mode operation. We observed that the
density of highly charged Kr ions and ion confinement time increase
with increasing mirror magnetic field strength. The plasma potential
dip becomes shallower with insertion of the electrode. Consequently,
when we increase the mirror magnetic field strength and insert the
electrode into the plasma, the beam intensities of highly charged ions
increase.
We have observed the enhancement of the Ar
11+
beam intensity from
the RIKEN 18 GHz electron cyclotron resonance ion source (ECRIS) when
using the electrode at the floating potential. We have ...successfully obtained
the beam intensity of 280 eµA for Ar
11+
at an extraction voltage of 15 kV.
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