Gadolinium-enhanced dynamic magnetic resonance imaging with endorectal coil for local staging of rectal cancer.

PURPOSE: The aim of this study was to evaluate the accuracy of dynamic gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) with endorectal coil for assessing tumor invasion based on simple classification criteria. MATERIALS AND METHODS: A total of 58 patients with operable primary rectal cancer underwent preoperative MRI. An enhancement pattern in Gd-enhanced dynamic MRI with regard to tumor penetration was clarified. Retrospectively, two observers independently scored T2-weighted MRI and T2-weighted MRI combined with Gd-enhanced dynamic MRI for tumor penetration using the following criteria: With Gd-enhanced dynamic MRI, T1 tumors showed an early enhanced line around the tumor as rim enhancement; T2 tumors appeared as black lines or double layers, as the muscularis propria kept its integrity; T3 tumors showed partial discontinuity of the muscularis propria as a dotted line and a perforated area as an interrupted line. A confidence level scoring system was used, and receiver operating characteristic curves were generated. RESULTS: There were no significant differences at the T1 stage. There were significant differences for observer 1 (P = 0.001 for observer 1) at the T2 stage. There were significant differences for both observers (P = 0.001 for observer 1 and P = 0.005 for observer 2) at the T3 stage. CONCLUSION: Our criteria for Gd-enhanced dynamic MRI were effective for T3 stage tumors.

The treatment outcome of patients undergoing breast-conserving therapy: the clinical role of postoperative radiotherapy.

BACKGROUND: Treatment outcome was evaluated in patients who underwent breast-conserving therapy and tangential irradiation. After verifying background factors including systemic therapy, the clinical efficacy of postoperative irradiation was investigated. METHOD: There were 708 study subjects, all of whom had early breast cancer treated between 1992 and 2002. The median follow-up period was 83 months. After breast-conserving surgery, in patients with negative surgical margins, only tangential irradiation at 48 Gy/24 fr was performed. In contrast, in those with positive surgical margins, 10 Gy of radiation boost to the tumor bed with electrons was administered after tangential irradiation with 50 Gy/25 fr. Treatment outcome was analyzed using the Kaplan-Meier method and Cox's proportional hazards regression model. RESULTS: The disease-free survival and no-recurrence rates within the ipsilateral breast after 5 years were 93.4 and 97.2%, respectively. Risk factors for recurrence within the ipsilateral breast included younger age of patient, the number of positive lymph nodes, and no endocrine therapy. However, the surgical margin was not a risk factor. Risk factors for relapse outwith the ipsilateral breast included younger age, the number of positive lymph nodes, and recurrence within the ipsilateral breast. CONCLUSIONS: From our analysis of 708 Japanese women who received breast-conserving therapy, which can be regarded as a standard method in Japan, the treatment outcome was compatible with previous reports from other countries.

Does contrast-enhanced ultrasound reveal tumor angiogenesis in pancreatic ductal carcinoma? A prospective study.

The purpose of this study is to evaluate tumor vascularity of pancreatic carcinoma noninvasively by contrast-enhanced ultrasound (US) and clarify the diagnostic value of tumor vascularity in subjects with nonresectable advanced pancreatic carcinoma. The study was approved by our institutional review board and written informed consent was obtained from all subjects. Twenty-seven subjects with advanced pancreatic ductal carcinoma were treated by chemoradiotherapy. Contrast-enhanced US, US guided biopsies and dynamic computed tomography (CT) were performed before and after the therapy. We assigned the intratumoral enhancement pattern of US as an enhanced ultrasound (EU) score, from 1 to 4, according to the degree of enhancement area. Intratumoral microvessel density (IMD) and average vessel diameter (AVD) were calculated by means of CD 34 immunostaining. Vascular endothelial growth factor (VEGF) staining was graded on a scale of 1 to 3. EU scores before chemoradiotherapy were compared with IMD, AVD, VEGF, histological grading and hepatic metastasis. After the therapy, local treatment response was evaluated by dynamic CT calculating the maximum area of the tumor, by comparing it with its size in pre- therapy. Subjects who had at least a 50% or more decrease of tumor size lasting more than 4 wk were estimated as partial response (PR), more than a 50% of increase progressive disease (PD) and if neither PR nor PD criteria were met, they were classified as stabled disease (SD). Next, EU scores were compared with IMD, AVD, VEGF and treatment response. Statistically significant differences were evaluated by Pearson's correlation, post-hoc, Spearman's rank correlation, Wilcoxon rank sum and Student's t-test. A p < 0.05 was defined as being statistically significant. Before the therapy, the EU score and IMD were significantly correlated (r = 0.50, p < 0.02), as was VEGF (r = 0.45, p < 0.05). The EU score and AVD were negatively correlated (r = - 0.56, p < 0.02). Significant correlation was found between the EU score and histological grading (p < 0.004). The EU score was higher in subjects who had hepatic metastasis compared with subjects who had no hepatic metastasis (p < 0.05). After chemoradiotherapy, 14 subjects exhibited PR, while 13 showed SD. None of the subjects showed PD. The EU score was smaller in PR than SD (p < 0.05). The EU score significantly decreased after the therapy in PR (p < 0.01) but not in SD. IMD and AVD did not significantly decrease in either PR or SD; however, VEGF decreased significantly in PR (p < 0.01) but not in SD. Contrast-enhanced US could reveal tumor vascularity of pancreatic ductal carcinoma and could be potentially useful to evaluate treatment effect of subjects who receive chemoradiotherapy. Further investigation will be needed to prove the usefulness of contrast-enhanced US.

High-intensity focused ultrasound induced apoptosis with caspase 3, 8, and 9/6 activation in rat hepatoma.

PURPOSE: The purpose of the present study is to investigate anticancer efficacy and apoptosis confirmed by caspase under several exposure conditions of high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Twenty-five rats with KDH-8 hepatoma were treated by HIFU at several acoustic energies to evaluate treatment efficacy. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst 33258 staining, and caspase 3, 8, and 9/6 activity was respectively assayed. RESULTS: The KDH-8 subcutaneous tumors were reduced by HIFU, and these rats survived longer than the nontreatment rats (P < 0.01). The minimal threshold of HIFU energy was 30 W × 1.0 s for tumor control and long-term survival. The tumors exposed to HIFU exhibited marked apoptotic features under conditions of less than 10 W × 1.0 s. In cultured KDH-8 cells, apoptosis was caused at less than 30 W × 1.0 s (P < 0.01), and more was induced as the energy went down. Caspase 3, 8, and 9/6 were more activated at low energy under 10 W × 1.0 s (P < 0.01), and caspase 8, which is death receptor dependent, was significantly more activated than caspase 9/6, which is mitochondria dependent (P < 0.01). CONCLUSION: HIFU-induced apoptosis in vivo and in vitro is one of the mechanisms for tumor control and is mediated by caspase 3, 8, and 9/6. The significantly greater activation of caspase 8 than of caspase 9/6 suggests that the apoptosis pathway induced by HIFU might be more mitochondria dependent than death receptor dependent. However, further examination will be needed.

Wall composition analysis of the human hepatic artery by intravascular ultrasound.

PURPOSE: The purpose of this study was to elucidate the wall layer appearance of the human hepatic artery shown by intravascular ultrasound (IVUS). METHODS: We evaluated the wall layer appearance of 57 human hepatic arteries from 36 cadavers. The thickness of the inner high-echoic layer and the second low-echoic layer of the arteries was measured by IVUS, and it was compared with that of the arterial intima and media, respectively. RESULTS: The thickness of the inner high-echoic layer was 0.2 ± 0.1 mm and that of the second low-echoic layer was 0.4 ± 0.1 mm, on IVUS. However, the histological thickness of the intima was 120 ± 45 µm and that of the media was 258 ± 71 µm. The media of the hepatic artery correlated significantly with the second low-echoic layer on IVUS (r = 0.62, P < 0.01). The diameter of the vessels measured on IVUS correlated significantly with that of the histological specimens (r = 0.89, P < 0.01). CONCLUSION: From our results, the three layers of the hepatic artery detected with IVUS may correspond to the intima, media, and adventitia, respectively.